Thesis submitted in fulfilment of the requirements for the degree DOCTOR TECHNOLOGIAE: ENGINEERING: CHEMICAL in the FACULTY OF ENGINEERING at the CAPE PENINSULA UNIVERSITY OF TECHNOLOGY 2014 / Several authors have reported on the use of alcohols – water /or mixed solvents to synthesise metal oxide nanoparticles. However, no systematic study has been carried out to evaluate the effect of mixed solvent on the particle characteristics, although considerable research has been reported, a gap still exists with regard to the effect of the alcohols as solvents on the growth kinetics of nanoparticles. To address these issues, four different alcohols, namely, methanol (MeOH), ethanol (EtOH), propanol (PrOH) and butanol (BuOH) were used as solvents in the synthesis of β-FeOOH particles. The effect of organic solvents on the growth kinetics of β-FeOOH nanorods has been evaluated for the first time in this study. Two-stage growth of akaganeite nanorods has been observed in BuOH and PrOH. The first growth stage follows a typical power law representing Ostwald ripening (OR) kinetic. The second stage was found to be asymptotic and obeyed oriented attachment (OA) kinetic. The proof of the OA kinetic also comes from the HRTEM images of the synthesised particles. Simultaneous occurrence of the two mechanisms was observed in the growth of the particles synthesised in EtOH and MeOH. The rate constants for OR kinetic, KOR, was found to be higher than the rate constant for OA kinetic, KOA, for different solvents used. Preamble The use of a mixed solvent is a new approach in the synthesis and processing of materials. Various researchers have stated that the surface tension of the solvent plays an important role in the formation of uniform nanorods. However, the effect of surface tension was not correlated with the particle growth, earlier, though the dielectric properties of the mixed solvents were only taken into account. Additionally, no quantitative or qualitative relationship was presented between surface tension and particle growth in the literature. In this work an attempt to correlate these two parameters (surface tension and particle growth) with the concentration of the precursor and temperature was made, resulting in an exponential relationship between KOR for the particle growth and surface tension of the alcohols. Furthermore, the relationship between surface tension and particle growth was validated by an independent study using statistically designed experiments to account for the influence of various process variables on the particle growth. The findings in this study obtained from both theoretical and experimental work provides an insight into the relationship between solvent surface tension and particle growth interactions, producing a new piece of information that will further promote our understanding of the formation mechanisms of β- FeOOH growth. The transformation temperature of akaganeite (β-FeOOH) nanorods to hematite (α-Fe2O3) particles was found to be solvent dependent. Thermogravimetric analysis and differential scanning calorimetry were performed to evaluate the effect of alcohol on the thermodynamic stability of the particles. Alcohol as solvent played a significant role in the dehydration property of the synthesised particles. The percentage mass loss of the particles at 300°C decreases linearly with increasing carbon number in the linear alkyl chain of the solvent. The effect of alcohol type on the particle morphology was found to be more pronounced at higher FeCl3 concentrations (>0.5M). Splitting of β-FeOOH nanorods was observed at FeCl3 concentration of 0.7M in BuOH. In PrOH, rectangular morphologies were obtained whereas nanoribbons resulted in surfactant-free conditions. It was found that the nature of anions (chloride vs. nitrate and sulphate) in the precursor salt also influenced the morphology.

Orientador: Carlos de Oliveira Paiva Santos / Coorientadora: Selma Gutierrez Antonio / Banca: Marlus Chorilli / Banca: Vinícius Danilo Nonato Bezzon / Banca: Flavio Machado de Souza Carvalho / Banca: Alexandre Urbano / Resumo: O refinamento de estruturas cristalinas pelo método de Rietveld (MR) consiste em ajustar um modelo estrutural a uma medida de difração. Essa é uma ferramenta eficiente para identificação e quantificação de estruturas polimórficas presentes em fármacos e excipientes. Uma forma avançada do método é o refinamento sequencial por Rietveld (RSR) que visa, a partir de um conjunto de difratogramas de uma mesma amostra, estudar o comportamento do material em função de uma variável externa (e.g. temperatura, pressão, tempo ou ambiente químico). No presente trabalho, com o objetivo de estudar as transições polimórficas e as expansões/contrações dos parâmetros de cela unitária (PCU) dos insumos farmacêuticos: espironolactona (SPR), lactose monoidratada (LACMH) e lactose anidra (LACA), empregou-se o RSR em medidas obtidas em diferentes temperaturas. O RSR foi eficiente para que os PCU fossem refinados até temperaturas próximas ao ponto de fusão dos materiais. Após o RSR, a partir da análise matemática dos PCU obtidos, foram propostas funções que regem a tendência desses parâmetros quando submetidos à variação de temperatura. Com essas funções modelaram-se os PCU em uma outra modalidade de refinamento, o refinamento paramétrico por Rietveld (RPR), assim, os PCU seguem a modelagem imposta pelas equações obtidas via RSR. O RPR mostrou-se mais eficiente nas análises, o que evitou perda de fases ou problemas de ajustes, resultando assim em informações mais precisas do sistema. Embora o RSR e R... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The crystal structural refinement by the Rietveld method (MR) consists of fitting a structural model to a diffraction measure. This is an efficient tool for identification and quantification of polymorphic structures present in drugs and excipients. An advanced way to use this method is the Sequential Rietveld Refinement (RSR), which aims, from a set of data of the same sample, to study the behavior of the material as a function of an external variable (e.g. temperature, pressure, time or chemical environment). In the present work, with the objective of studying the polymorphic transitions and the expansions / contractions of the unit cell parameters (PCU) of the pharmaceutical ingredients: spironolactone (SPR), lactose monohydrate (LACMH) and anhydrous lactose (LACA), the RSR in measurements obtained at different temperatures. The RSR was efficient so that the PCU were refined to temperatures close to the melting point of the materials. After the RSR, from the mathematical analysis of the obtained PCU, functions were proposed that govern the trend of these parameters when submitted to the temperature variation. With these functions the PCU were modeled in another modality of refinement, the Parametric Rietveld Refinement (RPR), thus, the PCU follow the modeling imposed by the equations obtained via RSR. The RPR was more efficient in the analyzes, which avoided loss of phases or problems of adjustments, resulting in more accurate information of the system. Although RSR and RP... (Complete abstract click electronic access below) / Doutor

No / The current work was undertaken to assess suitability of liquid crystalline phase for engineering of lactose crystals and their utility as a carrier in dry powder inhalation formulations. Saturated lactose solution was poured in molten glyceryl monooleate which subsequently transformed into gel. The gel microstructure was analyzed by PPL microscopy and SAXS. Lactose particles recovered from gels after 48 h were analyzed for polymorphism using techniques such as FTIR, XRD, DSC and TGA. Particle size, morphology and aerosolisation properties of prepared lactose were analyzed using Anderson cascade impactor. In situ seeding followed by growth of lactose crystals took place in gels with cubic microstructure as revealed by PPL microscopy and SAXS. Elongated (size approximately 71 mum) lactose particles with smooth surface containing mixture of alpha and beta-lactose was recovered from gel, however percentage of alpha-lactose was more as compared to beta-lactose. The aerosolisation parameters such as RD, ED, %FPF and % recovery of lactose recovered from gel (LPL) were found to be comparable to Respitose(R) ML001. Thus LC phase (cubic) can be used for engineering of lactose crystals so as to obtain particles with smooth surface, high elongation ratio and further they can be used as carrier in DPI formulations.