Orientador: Claudio Airoldi / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-21T09:21:18Z (GMT). No. of bitstreams: 1 Vieira_AdrianaPires_D.pdf: 2625082 bytes, checksum: 5ad150ad19ef89615a506cf16abb5e3b (MD5) Previous issue date: 2012 / Resumo: O biopolímero quitosana foi modificado quimicamente a fim de se potencializar suas propriedades. Duas sequências de reações foram realizadas: i) imobilização do metil acrilato seguido da cisteamina, obtendo-se os materiais QMA e QMAC, e ii) imobilização envolvendo o etilenossulfeto, acrilato de metila e cisteamina, obtendo-se os materiais, QE, QEMA e QEMAC. As estruturas correspondentes foram caracterizadas por análise elementar, espectroscopia na região do infravermelho, ressonância magnética nuclear no estado sólido C, termogravimetria, difração de raios X e microscopia eletrônica de varredura. Os novos biopolímeros foram testados para a aplicação em sorção dos cátions de chumbo e cádmio e também do corante aniônico azul reativo e do catiônico verde brilhante. Também foram aplicados para a imobilização e liberação controlada do fármaco ibuprofeno. Os novos biopolímeros obtidos mostraram-se bons sorventes frente aos cátions metálicos e ao corante aniônico. No estudo de cinética de sorção foram utilizadas as equações de pseudo primeira e segunda ordens a fim de verificar o mecanismo que envolve o processo, sendo que o de segunda ordem mostrou-se o mais adequado. Nos experimentos isotérmicos foram utilizadas as equações de Langmuir e Freundlich, onde o modelo de Langmuir foi o que apresentou melhor ajuste. Os materiais também foram utilizados para imobilização e liberação controlada do fármaco, na forma de pastilhas e filmes reticulados com glutaraldeído. Os experimentos mostraram que a liberação é sensível ao pH. As quitosanas quimicamente modificadas permitiram a redução da liberação do fármaco no fluido gástrico, uma vez que os grupos funcionais presentes causam uma diminuição na taxa de intumescimento a pH 1,2, em contraste com o comportamento ocorrido em pH 7,4 que simula o fluido intestinal, onde há um aumento na taxa de intumescimento. Em tais condições a carga negativa do ibuprofeno é eletrostaticamente repelida pela superfície negativa dos derivados da quitosana / Abstract: The chitosan biopolymer is chemically modified in order to enhance its properties.Two sequences of reactions were carried out: i) immobilization of methyl acrylate followed by cysteamine to yield materials QMA and QMAC, and ii) immobilization ethylene sulfide, methyl acrylate and cysteamine to yield materials QE, QEMA, QEMAC. The corresponding structures were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance in solid state C NMR, thermogravimetry, X-ray diffraction and scanning electron microscopy. The new polymers were tested for use in sorption of cations of lead and cadmium and also reactive blue dye anionic and cationic bright green. Were also applied to the immobilization and controlled release of drugs using ibuprofen as a model drug. The new polymers obtained proved to be good sorbents for the metallic cations and the anionic dye. In the sorption kinetics study were used equations first and second pseudo order to verify the mechanism that involves the process, and the second order proved to be the most appropriate. In isothermal experiments were used Langmuir and Freundlich equations, where the Langmuir model showed the best fit. The materials were also used for immobilization and controlled release of the drug in the form of tablets and film crosslinked with glutaraldehyde. The experiments show that the release is pH sensitive. The chemically modified chitosans possible to reduce the release of the drug in the gastric fluid, because functional groups present cause a decrease in swelling rate at pH 1.2. In contrast to the behavior that occurred at pH 7.4 simulated intestinal fluid, where there is an increase in the rate of swelling. Under such conditions the negative charge of ibuprofen is repelled electrostatically by the negative surface of the derivatives of chitosan / Doutorado / Quimica Inorganica / Doutora em Ciências

Orientador: Claudio Airoldi / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-21T09:22:45Z (GMT). No. of bitstreams: 1 Almeida_RamonKenneddeSousa_D.pdf: 5842282 bytes, checksum: 25fcb2d8b707fa65cc5cf6a492365f29 (MD5) Previous issue date: 2012 / Resumo: As sílicas mesoporosas SBA-15 e SBA-16 sintetizadas através do método hidrotérmico com os copolímeros direcionadores de estrutura P123 e F127 foram organofuncionalizadas com agentes sililantes que contêm grupos funcionais, como nitrogênio, oxigênio e enxofre. As sílicas foram caracterizadas por análise elementar, espectroscopia na região do infravermelho, ressonância magnética nuclear de carbono e silício no estado sólido, termogravimetria, área superficial, espalhamento de raios X a baixo ângulo, microscopia eletrônicas de varredura e transmissão. As caracterizações comprovam a efetivação das sínteses das sílicas SBA-15 e SBA-16 com estruturas hexagonal e cúbica, respectivamente. As sílicas organofuncionalizadas, mostraram maiores graus de ancoramento obtido quando funcionalizadas com organossilanos contendo nitrogênio. Além das sílicas, foram sintetizados carbonos mesoporosos usando as sílicas como direcionadores rígidos de estrutura. Os mesmos foram funcionalizados com anidrido malêico e subsequentes reações com água e hidreto de alumínio e lítio resultando em grupos carboxílicos e na redução dos mesmos, respectivamente. A efetividade da funcionalização foi comprovada, sobretudo por espectroscopia na região do infravermelho, termogravimetria, ressonância magnética de carbono e espectroscopia de fotoelétrons de raios X. Ensaios de liberação dos fármacos ibuprofeno e genfibrozila foram realizados nas sílicas SBA-15 e SBA-16. Os resultados mostraram que ibuprofeno é liberado de SBA-15 de forma constante e controlada por 77 h. Além disso, os perfis de liberação de genfibrozila mostraram que 67 % do fármaco foram liberados de ambas as sílicas, porém o tempo de equilíbrio foi 70 h quando usada SBA-15 e de 24 h quando usada SBA-16. Além disso, verificou-se que os dados tem um bom ajuste quando aplicado a modelo apropriado e que os mecanismos de liberação são regidos pela influencia da difusão e pelo tempo de liberação / Abstract: Mesoporous SBA-15 and SBA-16 silicas synthesized by hydrothermal method using P123 and F127 copolymers as structure directing agents were organofunctionalized with silylating agents containing functional groups, such as nitrogen, oxygen and sulfur. The silicas were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance of carbon and silicon nuclei in solid state, thermogravimetry, surface area, X-ray scattering at low angle, scanning electron microscopy and transmission. The characterizations demonstrated the effectiveness of the synthesis of SBA-15 and SBA-16 silicas with hexagonal and cubic structures, respectively. The organofunctionalized silicas showed that the obtained surface modification gave highest degrees of anchoring when functionalized with organosilanes containing nitrogen. Besides the silicas, were also synthesized mesopororous carbons using silicas as hard template, which were functionalized with maleic anhydride and subsequent reaction with water and lithium aluminum hydride, resulting in carboxylic groups due to the reduction process. The effectiveness of the functionalized was proven, mainly by infrared spectroscopy, thermogravimetry, 13C NMR and X-ray photoelectron. Assays with ibuprofen and gemfibrozil releasing were performed on SBA-15 and SBA-16 silicas and the results showed that the ibuprofen is released from SBA-15 in a constant and controlled form for 77 h. Furthermore, release profiles of gemfobrozil gave 67 % of the drug released from both silicas, however the equilibrium time were 70 h when used SBA-15 and 24 h for SBA-16. In addition, it was found that the data has good fitting when applied for appropriate model and the release mechanisms are governed by the influence of diffusion and release time / Doutorado / Quimica Inorganica / Doutor em Ciências

Orientadores: Angela Maria Moraes, Paulo de Tarso Vieira e Rosa, Hermínio Cipriano de Sousa / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica / Made available in DSpace on 2018-08-21T13:49:40Z (GMT). No. of bitstreams: 1 Veiga_ItiaraGoncalves_D.pdf: 7420007 bytes, checksum: 72fa5c4f048822ac905a8b95278e63f3 (MD5) Previous issue date: 2012 / Resumo: O corpo humano é recoberto por aproximadamente 2 m2 de pele, e lesões cutâneas, além de causarem danos físicos, mecânicos e térmicos, podem também afetar as funções fisiológicas de outros tecidos, gerando desordens fisiológicas. As membranas desenvolvidas para o tratamento de lesões de pele podem ser constituídas por vários tipos de polímeros, sendo a quitosana um dos mais estudados. Diversos polissacarídeos como alginato, xantana, pectina, goma guar e goma arábica, são capazes de formar complexos com a quitosana, podendo tal combinação contribuir para a melhoria das propriedades das membranas usadas como curativos. Neste contexto, o presente trabalho teve por objetivo o estabelecimento de metodologias de preparação e a caracterização de membranas de quitosana e outros biopolímeros, a fim de selecionar as formulações mais adequadas para uso como dispositivo de liberação controlada de fármacos, mais especificamente dos anti-inflamatórios não esteróides diclofenaco de sódio, cetoprofeno e piroxicam, utilizando três formas de incorporação (adição dos fármacos durante a formação da membrana, absorção de solução contendo o fármaco e impregnação de fármaco na presença de CO2 supercrítico). As membranas foram caracterizadas quanto à morfologia, à espessura, à resistência mecânica, à capacidade máxima de absorção de diferentes soluções aquosas, à perda de massa quando expostas a diferentes soluções aquosas simulando fluidos corpóreos, à sorção e permeabilidade ao vapor, à biocompatibilidade in vitro, à eficiência de incorporação do fármaco e à cinética de sua liberação. Membranas de quitosana associada com os polímeros xantana, pectina ou goma guar foram obtidas com sucesso. Estas membranas foram caracterizadas de acordo com as metodologias citadas anteriormente e apresentaram propriedades adequadas para os processos de incorporação. A incorporação de diclofenaco de sódio e piroxicam pelos três métodos propostos foi realizada, apresentando melhores resultados quando a adição dos fármacos foi realizada durante o processamento. Foi possível também incorporar o diclofenaco de sódio por absorção, porém foram observadas baixas eficiências de incorporação (inferiores a 2,7 %) na presença de meio supercrítico. Já para o piroxicam e o cetoprofeno foram obtidas baixas eficiências na incorporação por absorção (menores que 1%), mas resultados relevantes foram alcançados no processo em alta pressão. Nas condições testadas, os fármacos apresentaram liberação na primeira hora de contato, verificando-se que as membranas produzidas não apresentam capacidade de controle da liberação dos agentes ativos / Abstract: The human body is covered by approximately 2 m2 of skin. Skin lesions, in addition to cause physical, mechanical and/or thermal damages, may also affect the physiological functions of other tissues. Membranes developed to treat lesions can be constituted by several types of polymers, being chitosan one of the most studied. Polysaccharides such as alginate, xanthan, pectin, guar gum and arabic gum are capable to form complexes with chitosan that may contribute to improve the properties of membranes used as wound dressings. In this context, this work aimed the development of methodologies to prepare chitosan-based membranes and their characterization, intending to select adequate formulations to be used as delivery devices for three anti-inflammatory agents, namely sodium diclofenac, ketoprofen and piroxicam.The drugs were incorporated by three techniques: addition directly into the polymeric mixture, absorption of drug from solution and supercritical impregnation. The membranes were characterized regarding to morphology, thickness, tensile strength, strain at break, swelling capacity in different aqueous solutions, percentage of mass loss after prolonged exposure to the same media, vapor sorption and permeability, biocompatibility in vitro, drug incorporation efficiency and release kinetic. Chitosan membranes associated with xanthan, pectin or guar gum were successfully prepared and showed properties suitable for the processes of drug incorporation. The incorporation of sodium diclofenac and piroxicam through the three methods proposed was performed, and the most appropriate results were attained when drug addiction was performed during membrane processing. It was also possible to incorporate sodium diclofenac by absorption, but low incorporation efficiencies were observed (below 2.7%) in the presence of the supercritical fluid. For piroxicam and ketoprofen, low incorporation efficiencies were obtained by absorption (less than 1%), but significant results have been achieved in the process at high pressure. Under the conditions tested, the release of all drugs occurred in the first hour of contact, what indicated that the membranes produced were not capable to control the release of the active agents used / Doutorado / Desenvolvimento de Processos Biotecnologicos / Doutor em Engenharia Química

Orientadores: Ângela Maria Moraes, Paulo de Tarso Vieira e Rosa / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química / Made available in DSpace on 2018-08-21T17:27:21Z (GMT). No. of bitstreams: 1 Sacchetin_PriscilaSoaresCosta_D.pdf: 18116107 bytes, checksum: a46dd208ddd43d66ee2bb2d29e98cc46 (MD5) Previous issue date: 2012 / Resumo: No presente trabalho propôs-se a formação de carreadores orais compostos pelos polímeros sintéticos PLA (poli(L-ácido lático)), PLGA (poli(50/50 DL-ácido lático-co-glicólico)) e PCL (policaprolactona) para a construção de sistemas de liberação controlada de 17a-metiltestosterona (MT) pelo método de precipitação das soluções pelo uso de CO2 supercrítico como antisolvente. A influência da pressão, da concentração hormonal, dos polímeros e da vazão da solução polimérica foi analisada. Partículas de PLA com diâmetros entre 5,4 a 20,5 mm foram eficientemente produzidas, observando-se que o aumento na concentração da solução polimérica foi capaz de produzir partículas menores e que o aumento da vazão de solução polimérica resultou em aumento no tamanho das partículas produzidas. Não foram observados efeitos sobre a morfologia e distribuição de tamanhos das partículas com a variação da pressão. Notaram-se também nas partículas de PLA mudanças nas características mecânicas e físicas do polímero, como a redução da temperatura de transição vítrea do polímero. A produção de partículas de PLA na presença de MT resultou em aumento no tamanho médio e alterações nas características morfológicas superficiais das partículas. Praticamente não se observaram alterações na temperatura de transição vítrea e de fusão das partículas quando estas foram produzidas na presença de MT. As análises de potencial zeta das partículas mostraram que estas possuem forte tendência à floculação. Obtiveram-se também partículas de PLA/PCL a partir da mistura destes polímeros a razões de 1/9 a 1/1 m/m. Altas concentrações de PCL provocaram aumento no diâmetro médio das partículas, que se mostraram mais agregadas e rugosas. A eficiência de incorporação de MT nestas partículas variou de 25,6 a 64%. Verificou-se a alteração do comportamento térmico das partículas quando altas concentrações de MT foram empregadas, notando-se a formação de estruturas mais amorfas. As partículas de PLA/PLC não se mostraram estáveis quando submetidas aos ensaios de potencial zeta. Partículas de PLA/PLGA foram também produzidas, apresentando diâmetros médios que variaram de 23 a 98 mm. A eficiência de incorporação de MT foi igualmente ampla, entre 41 a 90%. A cristalinidade das partículas foi afetada pelo processo, sendo que a presença de MT levou à formação de estruturas mais amorfas e porosas. A cinética de liberação da MT foi analisada in vitro pela exposição das partículas a soluções com diferentes valores de pH. As menores taxas de liberação foram obtidas para as partículas de PLA, enquanto as partículas de PLA/PCL e PLA/PLGA produziram comportamentos similares entre si. Observou-se que a quantidade de partículas teoricamente necessárias durante o tratamento de reversão sexual de tilápias do Nilo variou conforme a composição dos dispositivos, sendo estes valores entre 34 a 88 g de partículas/kg de ração / Abstract: In this work, the aim was to produce oral carriers consisting of the synthetic polymers PLA (poly(L-lactic acid)), PLGA (poly(50/50 DL-lactide-co-glycolide)) and PCL (polycaprolactone) by the precipitation of the polymer solutions using supercritical CO2 as an antisolvent for the controlled release of 17?-methyltestosterone (MT). The influence of pressure, hormone and polymers concentration, as well as of the flow rate of the polymer solution on the formation of these devices was analyzed. PLA particles with diameters between 5.4 to 20.5 mm were efficiently produced; increases in the concentration of the polymer solution resulted in smaller particles, while increasing the flow rate of polymer solution caused an increase in particle mean diameter. No significant effects on morphology and size distribution of the particles were observed with pressure variation. Changes in the mechanical and physical characteristics of the PLA particles were also noticed, as reduction in the glass transition temperature of the polymer. PLA particles prepared in the presence of MT showed larger average diameters and changes in surface morphology. The presence of MT did not result in changes of the glass transition and fusion temperatures of the particles. Zeta potential analyzes showed that the particles have a strong tendency to flocculate when exposed to aqueous solutions. PLA/PCL particles were obtained from the mixture of these polymers at ratios from 1/9 to 1/1 w/w. High concentrations of PCL caused increased formation of particles with greater mean diameters, which were rougher and had a higher tendency to aggregate. The incorporation efficiency of MT ranged from 25.6 to 64%, accompanied by an increase in mean diameter. Changes in the thermal behavior of the particles were observed when high concentrations of MT were used, which led to the formation of more amorphous structures. PLA/PLC particles were not stable when subjected to tests of zeta potential. PLA/PLGA particles were also produced, with mean diameters ranging from 23 to 98 mm. The incorporation efficiency of MT was also broad, varying from 41 to 90%. The process affected the crystallinity of the particles, and the presence of MT led to more amorphous and porous structures. The behavior of the PLA, PLA/PCL and PLA/PLGA particles regarding the in vitro release kinetics of MT was analyzed through exposure of the obtained systems to different pH conditions. The lowest release rates were observed for PLA particles, while the PLA/PCL and PLA/PLGA particles showed similar performances. It was observed that the theoretical amount of particles needed for the sex reversal treatment of tilapia varied according to the composition of the devices (polymer type and ratio, as well the quantity of MT). Depending on the device, the daily required amounts of particles can vary between 34-88 g particles/kg of fish feed / Doutorado / Desenvolvimento de Processos Biotecnologicos / Doutor em Engenharia Química

Orientador: Carlos Raimundo Ferreira Grosso / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-03T18:23:17Z (GMT). No. of bitstreams: 1 Correa_RenataMukai_M.pdf: 13500100 bytes, checksum: 565403535c4481aa54c2bbd82994ce84 (MD5) Previous issue date: 2003 / Resumo: Este trabalho visou a produção de microcápsulas capazes de reter proteínas, para serem utilizadas na tentativa de substituição dos organismos vivos usados na alimentação de larvas de peixes. Quatro diferentes polissacarídeos: alginato, carragena, goma gela na e pectina; todos com capacidade de formação de gel por polimerização iônica foram utilizados, individualmente e em associação, para obtenção de cápsulas e microcápsulas. A fabricação se deu através de uma bomba peristáltica (cápsulas) e de um aspersor capilar com alta pressão (microcápsulas). Foram construídos diagramas de fase para determinação das regiões sol, gel e sinerése. Parâmetros como flutuabilidade, solubilidade, morfologia e tamanho das cápsulas e microcápsulas foram avaliados, sendo determinantes na posterior escolha e utilização de cápsulas e microcápsulas para fins voltados ao cultivo de peixes. A capacidade de liberação de proteína pela microcápsula foi investigada em matrizes úmidas e secas por liofilização, em períodos pré-determinados utilizando caseína (proteína modelo) e um sistema composto desta proteína com a introdução de gordura vegetal hidrogenada. Ensaios de digestibilidade in vitro foram conduzidos para verificar o acesso enzimático à proteína encapsulada. Os resultados apresentados pelos digramas de fase mostraram a capacidade da goma gelana e carragena de formarem géis sem adição de cálcio a partir das concentrações poliméricas de 0,75 e 1,2%, respectivamente. Os diagramas também indicaram a predominância de um dos polímeros componente da mistura (binária, ternária ou quaternária) utilizadas na fabricação das microcápsulas. Todas as microcápsulas estudadas mostraram insolúveis após a geleificação e cura. A flutuabilidade das cápsulas úmidas sem recheio variou de 21,7s (pectina-alginato) a 6,5s (carragena-alginato). A flutuabilidade das microcápsulas úmidas e secas por liofilização contendo proteína e gordura foram superiores a 4 horas. O tamanho variou de variou de 1,5 a 2 mm para cápsulas (microscópio estereoscópico) e de 8 a 870 mm (Iaser scattering) com média de 1501-1 para microcápsulas. Quanto a morfologia, as cápsulas e microcápsulas apresentaram formas esféricas em sua maioria, multinucleadas com distribuição do recheio por toda extensão da matriz. A secagem em liofilizador causou uma perda parcial da forma esférica das microcápsulas mantendo, no entanto, sua integridade física. Os sistemas poliméricos envolvendo somente proteína revelaram diferentes perfis de liberação proteíca, com maior liberação observada para matriz de alginato (100%) e menor para matriz obtida da mistura ternária pectina-gelana-alginato (10%), após 240 minutos em solução. Com a inclusão da gordura no sistema foi observada uma redução significativa (p<0,05) na liberação de proteína pela microcápsula. A menor liberação foi observada para as microcápsulas liofilizadas. A digestibilidade in vitro das microcápsulas indicou o acesso das enzimas à proteína encapsulada com níveis consideráveis (medida proteolítica >40% e queda de pH >70%) de digestibilidade comparada a caseína livre, para todos os sistemas estudados / Abstract: This research aimed at producing microcapsules capable of retaining proteins, with the objective of substituting the live organisms used in larval fish feed. Four different polysaccharides: alginate, carrageenan, gelan gum and pectin were used, all having the capacity to form gels by ionic polymerization both individually and in association, in order to produce capsules or microcapsules. The capsules were produced using a peristaltic bomb and the microcapsules using high -pressure capillary aspersion. Phase diagrams were constructed to determine the regions of sol, gel and syneresis. Parameters such as floatability, solubility, morphology and capsule/microcapsule size were evaluated, these parameters determining the subsequent choice and use of capsule or microcapsule in fish breeding. The protein liberating capacity of the microcapsule were investigated in moist and freeze-dried matrices after pre-determined periods, using casein (model protein) and a system composed by casein with the introduction of hydrogenated vegetable fat. In vitro digestibility trials were carried out to verify enzyme access to the encapsulated protein. The results presented by the phase diagrams showed the capacity of both gelan gum and carrageenan to form gels as from polymeric concentrations of 0.75 and 1.2% respectively, without the addition of calcium. The diagrams also indicated the predominance of one of the component polymers of the mixture (binary, ternary or quaternary) used in the production of microcapsules. Ali the microcapsules studied were shown to be insoluble after jellification and curing. The floatability of the moist unfilled microcapsules varied from 21,7s (pectin-alginate) to 6,5s (carrageenan-alginate). The floatability of both moist and freeze-dried microcapsules containing protein and fat was greater than 4 hours. The size of the capsules varied from 1,5 to 2 mm (§tereoscopic microscopy) and that of the microcapsules from 8 to 870 ).lm (Iaser scattering) with a mean of 150).lm. With respect to morphology, both the capsules and microcapsules were mostly spherical and multinucleated, the filling being distributed throughout the matrix. Freeze-drying resulted in a partial loss of the spherical form of the microcapsules, which nevertheless retained their physical integrity. The polymeric systems filled with only protein showed different protein liberation profiles, with greater liberation being observed for the alginate matrix (100%) and lesser liberation by the ternary mixture of pectin-gelan-alginate (10%), after 240 minutes in solution. The inclusion of fat in the system resulted in a significant reduction (p<0.05) in protein liberation by the microcapsule. The lowest degree of liberation was observed for the freeze-dried microcapsules. The in vivo digestibility of the microcapsules indicated access of the enzymes to the encapsulated protein, with considerable levels of digestibility (proteolytic mean >40% and a pH fall of >70%) in all the systems studied, as compared to that of free casein / Mestrado / Mestre em Alimentos e Nutrição

Doctor of Philosophy / Department of Horticulture and Natural Resources / Dale J. Bremer / Turfgrasses sequester and emit carbon dioxide, and emit nitrous oxide (N₂O) when fertilized with nitrogen and irrigated. Future water availability is a serious issue and drought restrictions may be imposed on turf managers while turf areas are subjected to traffic stress. My objectives in Chapter 2 were to: 1) quantify the magnitude and patterns of N₂O emissions and carbon (C) sequestration in zoysiagrass (Zoysia japonica Steud.); and 2) determine how irrigation (66% and 33% reference evapotranspiration [ET₀] replacement) and fertilization (polymer-coated urea, urea, and unfertilized) management may reduce N₂O emissions and enhance carbon sequestration. My objectives in Chapters 3 and 4 were to evaluate above- and below-ground responses of cool-season (C3) [Kentucky bluegrass (Poa pratensis L.) and perennial ryegrass (Lolium perenne L.)] and warm-season (C4) grasses {buffalograss [Buchloe dactyloides (Nutt.) Engelm] and zoysiagrass] at golf course-related mowing heights [1.6-cm (fairway) and 6.4-cm (rough)], with and without traffic during a simulated drought and subsequent recovery period (without traffic). In Chapter 2, N₂O emissions increased by 6.3% with more irrigation during summers and increased from 4.06 kg ha⁻¹ in unfertilized turf to 4.50, and 5.62 kg ha⁻¹ in polymer-coated urea and urea treated turf, respectively, during the 2-year study. There was no difference in C sequestration rates between a high vs. low input management schedule. The C sequestration rate was 0.952 Mg C ha⁻¹ yr⁻¹ for zoysiagrass when averaged across management schedules and depths. The use of a controlled-release fertilizer such as PCU compared to the use of a quick-release fertilizer and/or lower irrigation will reduce N₂O emissions in turfgrass. In Chapters 3 and 4, the better drought tolerance of C4 grasses led to more differences between traffic treatments within C4 than C3 grasses, but C4 grasses maintained the highest quality and green cover. Quality at rough- compared to fairway-height was more impacted by traffic. Decreasing soil moisture due to drought led to a minimal impact from traffic on soil bulk density, soil penetration resistance (SPR), and root measurements. During drought, SPR at deeper soil depths and fairway plots increased and exceeded the critical value of 2.0 MPa. Both C4 grasses and perennial ryegrass had larger root diameters, which may have led to better soil compaction resistance. Traffic during drought will have a negative and accelerated impacts above-ground, but minimal impact below-ground, which will vary with turf species and mowing height.

Volatile substances such as perfumes, insect pheromones and volatile corrosion inhibitors can be released into the atmosphere from polymer matrices. The release characteristics of the volatile substances depend on the original concentration of the substances, and also on the type and geometry of the matrix. The design of the matrix can be done with a trial and error process involving several iterations of tool making followed by testing of the release characteristics. However, this is a costly and time-consuming method. The objective of this study is to propose and evaluate a mathematical model based on Fick's second law of diffusion. The model can be used to predict the release profiles of volatile substances from polymer matrices based on the initial volatile concentration, matrix geometry and the coefficient of diffusion of the volatile through the polymer. The alcohols I-propanol, I-butanol, I-hexanol and I-octanol and the polymer ethylene-eo-vinyl acetate (EVA) were chosen as a model system for this study. The coefficients of diffusion of all the alcohols through the EVA were determined with the time lag test using a diffusion cell and polymer sheets. Several methods of making polymer sheets were evaluated. Injection moulded disks was the most suitable method for the system under consideration. Based on the results of the time lag tests, the proposed model was used to predict the release characteristics of the different alcohols from two EVA matrix designs. Injection moulded test pieces of both designs were prepared. All the test pieces contained ca. 10% of one of the alcohols. The test pieces were aged at ambient conditions and the release of the alcohols was monitored. It was found that the proposed model gave a good prediction of the residual mass of the dispensers, never diverging more than 10% from the experimental result. The experimental results tended to show faster release than predicted. This was expected since the model does not consider the effect of concentration on the coefficient of diffusion. It was concluded that the model gave accurate predictions of the release characteristics of the system investigated. It would be a useful tool in the design and development of polymer dispensers for volatile substances. The smaller number of tool modifications and release tests required will lead to cost and time savings in the development process. / Dissertation (M Eng (Chemical Engineering))--University of Pretoria, 2006. / Chemical Engineering / unrestricted

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.

This experimental work investigated the development and testing of a controlled release system for methionine. Methionine is one of the limiting amino acids for the milk production in dairy cows. The quantities of methionine which reach the small intestine are affected by the bacteria in the rumen which utilize methionine. A controlled release system which will offer a protective barrier for methionine may ensure that the methionine reaches the small intestine in sufficient quantities. The work involved the development of a coating around methionine crystals, which would act as a barrier, protecting it from the rumen conditions. Zein and kafirin proteins from maize and sorghum, respectively, were used as the principal coating components for the controlled release system. Two different approaches were used in the development of the controlled release system. First, the zein and kafirin proteins were tested for their ability to act as barriers for the controlled release of methionine, and second, zein and kafirin microparticles were used as the controlled release agents. Relatively successful, laboratory-scale methods were developed for coating the methionine with the proteins and the microparticles. Protein coatings were made by addition of methionine crystals to acid-dissolved proteins which led to the formation of a protein/methionine matrix. For coating the methionine with microparticles, glacial acetic acid was used to fuse microparticles around the methionine crystals. Dissolution assays were performed to test the release of methionine from the coatings under simulated rumen conditions. Both the zein and kafirin and microparticle coatings exhibited a barrier effect for methionine. The barrier effects of these coatings were influenced by several factors. Increasing the proportion of the coating agents led to improved barrier properties. However, this only occurred until a certain proportion of coating agent was present (50%), after which the barrier properties no longer increased. Heat treatment of the coatings also increased the barrier properties of the coatings. This may be due to the formation of disulphide cross-links being formed during the application of heat. When a simple extrusion method was used to form the coatings, the barrier properties also improved in comparison to those coatings which were not formed using extrusion. When producing the microparticles, it was found that only the laboratory extracted kafirin preparation with 85% (db) protein formed microparticles. It was hypothesized that microparticle formation might be related to the purity of the protein preparations. Scanning electron microscopy of the coatings after the dissolution tests and pepsin digestion revealed pores on the surface of the coating. These were probably where the methionine leached from the coating into the dissolution medium. The protein coatings did act as partial barriers, extending the release of methionine. From the release curves of methionine from the coatings, it could be seen that a sustained release of methionine occurred over a period of time, rather than a controlled release of methionine at a certain time. The aim of the application was thus only partially achieved as a complete protective barrier for methionine was not obtained from the protein coatings. No significant difference between the barrier properties of the coatings prepared from the proteins themselves and the microparticles were found. However, when based on equal protein purity the kafirin protein coatings showed the most effective barrier properties. Further research regarding kafirin coatings as a controlled release agent is recommended based on the results of the above named calculation. This research would entail investigating various coating technologies and methods. / Dissertation (MSc)--University of Pretoria, 2011. / Food Science / unrestricted