Indentation hardness, H, has been widely used to characterize the mechanical properties of materials for more than a century because of the following advantages of this technique; (1) it requires small sample and (2) the test is non destructive in nature. Recent technological advances helped in the development of instrumented indentation machines which can record the load, P, vs. displacement, h, data continuously during indentation with excellent load and displacement resolutions. From these, H and the elastic modulus, E, of the indented material can be obtained on the basis of the ‘contact area’ of the indentation at the maximum load. The estimation of true contact area becomes difficult during ‘pile-up’ and ‘sink-in’, commonly observed phenomena while indentation of a low and high strain hardened materials. In order for the better understanding of these phenomena it is important to understand the plastic flow distribution under indenters. It is also important for the prediction of elastic-plastic properties from the P-h data. Recently, there have been considerable theoretical and simulation efforts on this front with a combination of dimensional analysis and finite element simulations. One of the important input parameter for the dimensional analysis is the ‘representative strain’ under the indenter, which is a strong function of the indenter geometry. However there is no comprehensive understanding of the representative strain under the indenter despite several studies till date. One objective of the present thesis is to conduct an experimental analysis of the plastic flow during the sharp indentation. The plastic zone size and shape under conical indenters of different apex angles in a pure and annealed copper were examined by employing the subsurface indentation technique to generate the hardness map. From these isostrain contours are constructed joining the data having similar strain values. The following are the key observations. (1) The plastic strain contours are elliptical in nature, spreading more along the direction of the indenter axis than the lateral direction. (2) The magnitude of the plastic strain in the contact region decreases with increasing the indenter angle. (3) The strain decay in the indentation direction follow a power-law relation with the distance. The estimated representative strains under the indenters, computed as the volume average strain within the elastic-plastic boundary, decreases with increasing indenter angle. We also performed finite element simulations to generate plastic flow distribution under the indenter geometries and compared with the experimental results. The results suggest that the experimental and computed average strains match well. However, the plastic strain contours do not, suggesting that further detailed understanding of the elasto-plastic deformation underneath the sharp indenter is essential before reliable estimates of plastic properties from the P-h curves can be made routinely. The second objective of this thesis is to understand plastic flow in amorphous alloys. It is now well established that plastic deformation in metallic glasses is pressure sensitive, owing to the fundamentally different mechanisms vis-à-vis the dislocation mediated plastic flow in crystalline metals alloys. Early work has shown that the pressure sensitivity of amorphous alloys gets reflected as high constraint factor, C (hardness to yield stress ratio), which sometimes exceed 3.0. In this thesis, we study the temperature dependence of pressure sensitive plastic flow in bulk metallic glasses (BMGs) using C as the proxy for the pressure sensitivity. Experiments on three different BMGs show that C increases with temperature hence the pressure sensitivity. In addition we have carried out finite element simulations to generate P-h curves for different levels of pressure sensitivities and match them with the experimental curves that are obtained at different temperatures. Simulations predict that higher pressure sensitivity index values are required to match the experimental curves at high temperatures confirming that the pressure sensitivity increases with increasing temperature. The fundamental mechanisms responsible for the increase in pressure sensitivity are discussed in detail. Finally we pose a question, is the increase in pressure sensitivity with temperature is common to other amorphous materials such as strong amorphous polymers? In order to answer this question we have chosen PMMA, a strong amorphous polymer. In this study also we have taken C as a proxy to index the pressure sensitivity. Indentation stress-strain curves are constructed at different temperature using spherical indentation experiments. The C values corresponding to different temperatures are determined and plotted as a function of temperature. It is found that C increases with temperature implying that the pressure sensitivity of amorphous polymers also increases with temperature. The micro-mechanisms responsible for the increase in pressure sensitivity are sought.

No description available.

It is a well-known fact that drugs can exist in different solid-state forms. These solid-state forms can be either crystalline or amorphous. Furthermore, significant differences are identified between the different solid-state forms of the same drug. Physico-chemical properties that are affected by the solid-state include: melting point, solubility, dissolution rate, stability, compressibility, processability, to name but a few. During the last two decades a significant amount of attention was directed towards the amorphous solid-state forms of drugs. The amorphous form is the direct opposite of the crystalline solid-state. While crystalline forms are constituted by unit cells arranged in a repetitive and structured nature, amorphous forms do not have a long-range order. This lack of order leads to an increase in the Gibbs free energy of such compounds which in turn leads to increased dissolution and solubility. The advantage of improved aqueous solubility and dissolution is a sought after characteristic within the pharmaceutical industry. Improved solubility ultimately could lead to improved bioavailability of a drug. In this study the amorphous nature and stability of amorphous azithromycin was studied. Although previous studies reported that amorphous azithromycin can be easily prepared, there is not a significant amount of data available on the stability of the amorphous form. Furthermore, the effect of milling, mixing, compression, handling and storage on the amorphous form was also investigated. This study showed that amorphous azithromycin remains stable during milling, mixing and compression. A compatibility study on azithromycin when mixed with tableting excipients showed some incompatibilities and this was helpful information to assist with the choice of excipients to be included in the tablet formulation. During the formulation study it became evident that good formulation strategies can greatly improve the flow properties of a drug. The stability of amorphous azithromycin was also studied. During this phase of the study an atypical stability indicating method was used in order to determine and demonstrate the stability of amorphous azithromycin. Dissolution studies were used to illustrate the stability of amorphous azithromycin due to the fact that dissolution is the only method that indicates the phenomena of solution-mediated phase transformation of an amorphous form to a stable crystalline form. During the stability study of six months at 40°C ± 75% RH no recrystallisation of the amorphous form to the crystalline form occurred. It was concluded that amorphous azithromycin will remain stable during processing steps, product formulation and manufacturing as well as during storage for a period of six months at elevated temperature and humidity. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

It is a well-known fact that drugs can exist in different solid-state forms. These solid-state forms can be either crystalline or amorphous. Furthermore, significant differences are identified between the different solid-state forms of the same drug. Physico-chemical properties that are affected by the solid-state include: melting point, solubility, dissolution rate, stability, compressibility, processability, to name but a few. During the last two decades a significant amount of attention was directed towards the amorphous solid-state forms of drugs. The amorphous form is the direct opposite of the crystalline solid-state. While crystalline forms are constituted by unit cells arranged in a repetitive and structured nature, amorphous forms do not have a long-range order. This lack of order leads to an increase in the Gibbs free energy of such compounds which in turn leads to increased dissolution and solubility. The advantage of improved aqueous solubility and dissolution is a sought after characteristic within the pharmaceutical industry. Improved solubility ultimately could lead to improved bioavailability of a drug. In this study the amorphous nature and stability of amorphous azithromycin was studied. Although previous studies reported that amorphous azithromycin can be easily prepared, there is not a significant amount of data available on the stability of the amorphous form. Furthermore, the effect of milling, mixing, compression, handling and storage on the amorphous form was also investigated. This study showed that amorphous azithromycin remains stable during milling, mixing and compression. A compatibility study on azithromycin when mixed with tableting excipients showed some incompatibilities and this was helpful information to assist with the choice of excipients to be included in the tablet formulation. During the formulation study it became evident that good formulation strategies can greatly improve the flow properties of a drug. The stability of amorphous azithromycin was also studied. During this phase of the study an atypical stability indicating method was used in order to determine and demonstrate the stability of amorphous azithromycin. Dissolution studies were used to illustrate the stability of amorphous azithromycin due to the fact that dissolution is the only method that indicates the phenomena of solution-mediated phase transformation of an amorphous form to a stable crystalline form. During the stability study of six months at 40°C ± 75% RH no recrystallisation of the amorphous form to the crystalline form occurred. It was concluded that amorphous azithromycin will remain stable during processing steps, product formulation and manufacturing as well as during storage for a period of six months at elevated temperature and humidity. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

Metallic glass is a class of materials which have a disordered structure of atoms, due to this, glasses lack grains and grain boundaries, which are present in their crystalline counterparts. Metallic glasses have many interesting properties worth investigating, such as high corrosion resistance or high mechanical strength. However, metallic glasses are metastable and will therefore crystallise if heated above the crystallisation temperature. MoSiZr alloys have been studied and to gain knowledge of how the composition affects the crystallisation temperature, which enables further improvement of thermal stability. Crystallisation temperatures of the MoSiZr alloys were investigated by heat treatments in vacuum and ex-situ X-ray diffraction and X-ray reflectivity analysis. The highest thermal stability of the alloys was exhibited by M48Si48Zr4, Mo43Si50Zr7, Mo50Si40Zr10 and Mo45Si43Zr12, they remained amorphous after heat treatment at 1073 K. The resulting crystalline phases are Mo3Si, Mo5Si3 and ZrO2. Oxidation of Zr in the alloys is present only when the Zr content is at least 10 at%, crystallisation is otherwise mainly driven by formation of Mo3Si. Further improvement of the thermal stability is possible by introducing new alloying elements at the cost of those that promote crystallisation. Keeping the content of Zr below 10 at% is of great importance to prevent oxidation.

With the advance of combinational chemistry and high throughput screening, an increasing number of pharmacologically active compounds have been discovered and developed. A significant proportion of those drug candidates are poorly water-soluble, thereby exhibiting limited absorption profiles after oral administration. Therefore, advanced formulation and processing technologies are demanded in order to overcome the biopharmaceutical limits of poorly water-soluble drugs. A number of pharmaceutical technologies have been investigated to address the solubility issue, such as particle size reduction, salt formation, lipid-based formulation, and solubilization. Within the scope of this dissertation, two of the pharmaceutical technologies were investigated names thin film freezing and hot-melt extrusion. The overall goal of the research was to improve the oral bioavailability of poorly water-soluble drugs by producing amorphous solid dispersion systems with enhanced wetting, dissolution, and supersaturation properties. In Chapter 1, the pharmaceutical applications of hot-melt extrusion technology was reviewed. The formulation and process development of hot-melt extrusion was discussed. In Chapter 2, we investigated the use of thin film freezing technology combined with template emulsion system to improve the dissolution and wetting properties of itraconazole (ITZ). The effects of formulation variables (i.e., the selection of polymeric excipients and surfactants) and process variables (i.e., template emulsion system versus cosolvent system) were studied. The physic-chemical properties and dissolution properties of thin film freezing compositions were characterized extensively. In Chapter 3 and Chapter 4, we investigated hot-melt extrusion technology for producing amorphous solid dispersion systems and improving the dissolution and absorption of ITZ. Formulation variables (i.e., the selection of hydrophilic additives, the selection of polymeric carriers) and process variables (i.e., the screw configuration of hot-melt extrusion systems) were investigated in order to optimize the performance of ITZ amorphous solid dispersions. The effects of formulation and process variables on the properties of hot-melt extrusion compositions were investigated. In vivo studies revealed that the oral administration of advanced ITZ amorphous solid dispersion formulations rendered enhanced oral bioavailability of the drug in the rat model. Results indicated that novel formulation and processing technologies are viable approaches for enhancing the oral absorption of poorly water-soluble drugs. / text

No description available.

In most cases, organic materials exist in the solid phase as polymorphs, solvatomorphs or amorphous forms. Physico-chemical properties in the solid-state are all affected primarily in terms of dissolution, solubility, bioavailability, stability and processability. Therefore investigation into the polymorphic behaviour of APIs has become a mandatory part of drug characterisation studies by pharmaceutical companies (Giron, 2001). The influence polymorphism has on bioavailability and the need for the development of drugs in the amorphous form have instigated regulatory bodies such as the FDA to require solid-state characterisation of pharmaceuticals (Strachan et al., 2005). Subsequently a study was conducted to determine the physico-chemical properties of two poorly watersoluble macrolides; clarithromycin and spiramycin. Characterisation methods included: XRPD, IR, TGA, DSC, SEM, Karl Fischer titration, solubility and stability studies. Recrystallisations of spiramycin from various solvents indicated that this API mainly exists in the amorphous form. The DSC proved to be of little value in the characterisation of this particular macromolecular antibiotic, since wide inter-sample variations were mostly obtained. TGA results showed higher solvent uptake than expected. This was ascribed to the amorphous, sponge-like character of this drug. For the sake of reproducibility and quality of the results, characterisation of spiramycin was more reliant on spectroscopic and crystallographic methods. Samples generated from 2- butanol, chloroform, ethyl acetate, 1.4-dioxane, methanol, n-propanol, iso-propanol and tetrahydrofuran showed characteristic peaks in the range of 2000-2400 cm-1 that were not present in the IR spectrum of the raw material. Conversely, the XRPD patterns were all identical, exhibiting a characteristic “halo” pattern with no detectable Bragg diffraction peaks. A solubility assessment showed no significant differences between the raw material and the recrystallisation products. In fact the raw material seemed to be the form with the highest solubility, albeit it only by a small margin. According to the literature, clarithromycin exists in five forms. Form 0 exists as a solvate, form I is a metastable form, form II is the stable form (Liu & Riley 1998; Deshpande et al., 2006), form III is a solvate of acetonitrile (Liu et al., 2003; Liang & Yao, 2008) and form IV is a hydrate (Avrutov et al., 2003). The stable form II is used in formulations currently on the market. A follow-up study was done relating to a study performed by De Jager (2005). The raw material (form II) was recrystallised from acetonitrile, chloroform and ethyl acetate. Two new crystal forms were prepared from chloroform and acetonitrile. With the necessary driving force, both of these crystals forms are able to convert to the thermodynamically stable form II. In addition, a solvate recrystallised from chloroform together with its corresponding desolvate, showed a 4 and 1.5 fold respective increase in solubility when compared to the raw material. The recrystallisations from ethyl acetate delivered crystals with an XRPD pattern similar to form II. This proved that clarithromycin can be recrystallised directly from this solvent without the need of an additional conversion step, as was the case in the study done by De Jager (2005). / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2013

chemical partitioning of Cobalt-containing soft magnetic amorphous and nanocomposite materials has been investigated with particular focus on its consequences on these materials’ nanostructure and electrical resistivity. Theory, models, experiment, and discussion in this regard are presented on this class of materials generally, and are detailed in particular on alloys of composition, (Fe65Co35)79.5+xB13Si2Nb4-xCu1.5, for X={0- 4at%}, and Co-based, Co76+YFe4Mn4-YB14Si2Nb4, for Y={0-4at%}. The context of this work is within the ongoing efforts to integrate soft magnetic metal amorphous and nanocomposite materials into electric motor applications by leveraging material properties with motor topology in order to increase the electrical efficiency and decrease the size, the usage of rare-earth permanent magnets, and the power losses of electric motors. A mass balance model derived from consideration of the partitioning of glass forming elements relates local composition to crystal state in these alloys. The ‘polymorphic burst’ onset mechanism and a Time-Temperature- Transformation diagram for secondary crystallization are also presented in relation to the partitioning of glass forming elements. Further, the intrinsic electrical resistivity of the material is related to the formation of virtual bound states due to dilute amounts of the glass forming elements. And lastly, a multiphase resistivity model for the effective composite resistivity that accounts for the amorphous, crystalline, and glass former-rich amorphous regions, each with distinct intrinsic resistivity, is also presented. The presented models are validated experimentally on the Co-containing alloys by Atom Probe Tomography performed through collaboration with Pacific Northwestern National Laboratory.

Ph.D. / The aim of this study was the development of a new technology for the manufacturing of amorphous silicon (a-Si:H) solar cells on flexible substrates. Kapton R , a commercially available polymer, was used as a substrate to this end. The use of such a polymer, as opposed to glass, results in dramatic savings and also affords the possibility for technological innovation. From the start the project was planned to develop and commission a medium-scale pilot plant manufacturing process. The project thus consisted of two sections: the design, fabrication and implementation of a large-area deposition system, as well as research and development of the materials and cells. A pilot plant was developed and successfully implemented. The optimization of the reactor resulted in very homogeneous materials with good electrical- and optical characteristics. The individual materials were optimized and incorporated into the standard cell configuration (on glass). This process was then transferred to kapton and the configuration was optimized. The use of kapton, as opposed to glass, implies the growth of silicon on a metal film on the kapton. This process leads to a number of phenomena occurring in cells on kapton which do not occur in standard cells on glass. The phenomena include the crystallization of a-Si:H at low temperatures, degradation of the material properties and unwanted microstructure. The origin of these phenomena can be linked to the high occurence of metal/Si-interdiffusion. It was found that this inter-diffusion can be decreased by the insert i on of a thin ZnO buffer layer between the back metal contact and the a-Si:H. The flexible cells were successfully developed and optimized for large areas. An operational manufacturing process was thus developed and the product of this study can now be applied successfully in practical applications.