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Evaluation and comparison of the physical properties and drug release characteristics of directly compressible lactose–based filler/binders / Bettie van der Walt Erasmus (Alta)Erasmus, Bettie van der Walt January 2010 (has links)
Direct compression has gained significant interest since its advent in the late 1950's due to its potential ease compared to wet granulation. The primary prerequisites for powders used in direct compression are (i) good flow properties (ii) good compressibility and (iii) an acceptable dilution potential to accommodate a relative high percentage of active ingredient. Several filler/binders have been manufactured especially for direct compression and co–processing is one of the recent methods used to produce good compressible excipients with acceptable flow properties. In this study, lactose–based filler/binders were used which included simple and modified lactose materials (Granulac, Lactopress, Flowlac and Tablettose) as well as co–processed excipients (Starlac, Cellactose and Microcelac).
A comprehensive literature study on direct compression revealed the importance of the physical properties of filler/binders such as interparticle forces, particle shape, particle size and distribution, powder density, particle surface structure and particle packing geometry which influence the flow of powders. All the materials were subjected to the various tests available to evaluate powder flow, namely (i) angle of repose (AoR), (ii) critical orifice diameter (COD), (iii) flow rate and percentage compressibility (%C) in terms of the powders' bulk and tap densities. The results of these tests confirmed the expected flow properties of the various filler/binders, with only one material exhibiting extremely poor flow properties. The following rank order in terms of all flow tests conducted was established; Starlac >> Microcelac ~ Flowlac >> Cellactose > Tablettose > Lactopress >>> Granulac. The co–processed filler/binders presented with superior flow compared to the other lactose–based materials.
During the next phase of the study, the compaction properties of the various fillers were evaluated, employing direct compression. Compacts of pure filler were tabletted on an eccentric tablet press at different compression pressures (manipulated by the upper punch setting of the tablet press). The modified lactose filler/binders (Lactopress, Flowlac and Tablettose) exhibited unexpectedly poor compression profiles, where the co–processed filler/binders (Starlac, Cellactose and Microcelac) produced compacts with acceptable appearance and compact properties. Two lubricants (Mg–St or Pruv), which were tested separately in formulations were added since no compacts could be produced from the pure filler/binders. None of the modified lactose filler/binders, in combination with a lubricant, were able to produce an acceptable compact, since lamination occurred during compression. The co–processed filler/binders produced satisfactory compacts with the addition of a lubricant, but lactose–cellulose fillers (Cellactose and Microcelac) also required the inclusion of a disintegrant (Ac–Di–Sol) to induce satisfactory compact disintegration.
Poor compressible active ingredients (paracetamol), which exhibit very poor flow properties, are usually difficult to use during direct compression. Many excipients (tested in this study) are formulated to accommodate these drugs and produce acceptable functional tablets. After identifying the best filler/binders (co–processed fillers), according to their flow and compressible properties, paracetamol was added to the formulations. During a pilot study, the percentage paracetamol these fillers could accommodate in a 400 mg tablet was determined. Both Microcelac and Cellactose could accommodate 24.5% w/w paracetamol, whilst Starlac could only accommodated 19.5% w/w. Paracetamol is well known for its tendency to cause tablet capping and lamination. An acceptable upper punch setting range (20–22) was chosen for tabletting, followed by quality control tests done. All three formulations produced suitable tablets for testing and exhibited good tablet properties. All tablets disintegrated within two minutes, with hardness profiles between 120 N and 148 N and friability percentages less than 1%.
Dissolution studies, however, are probably the ultimate test to distinguish between the capability of filler/binders to release the optimum percentage drug after disintegration. Dissolution studies were done on all three formulations using the AUC (area under the curve) and IDR (initial drug release) as parameters to evaluate drug release. All tablets exhibited high initial dissolution rates (between 0.018 - 0.023 mg/min/ml) and 100% drug release was observed. Starlac presented with a lower amount of drug released compared to the other two, but can be explained by the lower percentage (19.5%) paracetamol present in the formulation.
It was once again confirmed that the physical and compressible properties of potential directly compressible filler/binders play a major role in direct compression. It was concluded that co–processed filler/binders (Starlac, Microcelac and Cellactose) definitely exhibited better tabletting properties during direct compression. They were able to accommodate a certain percentage of paracetamol, although it was expected that they would accommodate a higher amount (at least 50% of total tablet weight). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.
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Evaluation and comparison of the physical properties and drug release characteristics of directly compressible lactose–based filler/binders / Bettie van der Walt Erasmus (Alta)Erasmus, Bettie van der Walt January 2010 (has links)
Direct compression has gained significant interest since its advent in the late 1950's due to its potential ease compared to wet granulation. The primary prerequisites for powders used in direct compression are (i) good flow properties (ii) good compressibility and (iii) an acceptable dilution potential to accommodate a relative high percentage of active ingredient. Several filler/binders have been manufactured especially for direct compression and co–processing is one of the recent methods used to produce good compressible excipients with acceptable flow properties. In this study, lactose–based filler/binders were used which included simple and modified lactose materials (Granulac, Lactopress, Flowlac and Tablettose) as well as co–processed excipients (Starlac, Cellactose and Microcelac).
A comprehensive literature study on direct compression revealed the importance of the physical properties of filler/binders such as interparticle forces, particle shape, particle size and distribution, powder density, particle surface structure and particle packing geometry which influence the flow of powders. All the materials were subjected to the various tests available to evaluate powder flow, namely (i) angle of repose (AoR), (ii) critical orifice diameter (COD), (iii) flow rate and percentage compressibility (%C) in terms of the powders' bulk and tap densities. The results of these tests confirmed the expected flow properties of the various filler/binders, with only one material exhibiting extremely poor flow properties. The following rank order in terms of all flow tests conducted was established; Starlac >> Microcelac ~ Flowlac >> Cellactose > Tablettose > Lactopress >>> Granulac. The co–processed filler/binders presented with superior flow compared to the other lactose–based materials.
During the next phase of the study, the compaction properties of the various fillers were evaluated, employing direct compression. Compacts of pure filler were tabletted on an eccentric tablet press at different compression pressures (manipulated by the upper punch setting of the tablet press). The modified lactose filler/binders (Lactopress, Flowlac and Tablettose) exhibited unexpectedly poor compression profiles, where the co–processed filler/binders (Starlac, Cellactose and Microcelac) produced compacts with acceptable appearance and compact properties. Two lubricants (Mg–St or Pruv), which were tested separately in formulations were added since no compacts could be produced from the pure filler/binders. None of the modified lactose filler/binders, in combination with a lubricant, were able to produce an acceptable compact, since lamination occurred during compression. The co–processed filler/binders produced satisfactory compacts with the addition of a lubricant, but lactose–cellulose fillers (Cellactose and Microcelac) also required the inclusion of a disintegrant (Ac–Di–Sol) to induce satisfactory compact disintegration.
Poor compressible active ingredients (paracetamol), which exhibit very poor flow properties, are usually difficult to use during direct compression. Many excipients (tested in this study) are formulated to accommodate these drugs and produce acceptable functional tablets. After identifying the best filler/binders (co–processed fillers), according to their flow and compressible properties, paracetamol was added to the formulations. During a pilot study, the percentage paracetamol these fillers could accommodate in a 400 mg tablet was determined. Both Microcelac and Cellactose could accommodate 24.5% w/w paracetamol, whilst Starlac could only accommodated 19.5% w/w. Paracetamol is well known for its tendency to cause tablet capping and lamination. An acceptable upper punch setting range (20–22) was chosen for tabletting, followed by quality control tests done. All three formulations produced suitable tablets for testing and exhibited good tablet properties. All tablets disintegrated within two minutes, with hardness profiles between 120 N and 148 N and friability percentages less than 1%.
Dissolution studies, however, are probably the ultimate test to distinguish between the capability of filler/binders to release the optimum percentage drug after disintegration. Dissolution studies were done on all three formulations using the AUC (area under the curve) and IDR (initial drug release) as parameters to evaluate drug release. All tablets exhibited high initial dissolution rates (between 0.018 - 0.023 mg/min/ml) and 100% drug release was observed. Starlac presented with a lower amount of drug released compared to the other two, but can be explained by the lower percentage (19.5%) paracetamol present in the formulation.
It was once again confirmed that the physical and compressible properties of potential directly compressible filler/binders play a major role in direct compression. It was concluded that co–processed filler/binders (Starlac, Microcelac and Cellactose) definitely exhibited better tabletting properties during direct compression. They were able to accommodate a certain percentage of paracetamol, although it was expected that they would accommodate a higher amount (at least 50% of total tablet weight). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.
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Timing a hedge decision : the development of a composite technical indicator for white maize / Susari Marthina GeldenhuysGeldenhuys, Susari Marthina January 2013 (has links)
The South African white maize market is considered to be significantly more volatile than any other agricultural product traded on the South African Futures Exchange (SAFEX). This accentuates the need to effectively manage price risk, by means of hedging, to ensure a more profitable and sustainable maize production sector (Geyser, 2013:39; Jordaan, Grové, Jooste, A. & Jooste, Z.G., 2007:320). However, hedging at lower price levels might result in significant variation margins or costly buy–outs in order to fulfil the contract obligations. This challenge is addressed in this study by making use of technical analysis, focusing on the development of a practical and applicable composite technical indicator with the purpose of improving the timing of price risk management decisions identified by individual technical indicators. This may ultimately assist a producer in achieving a higher average hedge level compared to popular individual technical indicators.
The process of constructing a composite indicator was commenced by examining the prevailing tendency of the market. By making use of the Directional Movement Index (DMI), as identified in the literature study, the market was found to continually shift between trending prices (prices moving either upwards or downwards) and prices trading sideways. Consequently, implementing only a leading (statistically more suitable for trading markets) or lagging (statistically more suitable for trending markets) technical indicator may generate false sell signals, as demonstrated by the application of these technical indicators in the white maize market. This substantiated the motivation for compiling a composite indicator that takes both leading and lagging indicators into account to more accurately identify hedging opportunities. The composite indicator made use of the Relative Strength Index (RSI) and Stochastic oscillator as leading indicators, and the Exponential Moving Average (EMA) and Moving Average Convergence Divergence (MACD) as lagging indicators. The results validated the applicability of such a composite indicator, as the composite indicator outperformed the individual technical indicators in the white maize market. The composite indicator achieved the highest average hedge level, the lowest average sell signals generated over the entire period, as well as the highest average hedge level as a percentage of the maximum price over the entire period. Hence, the composite indicator recognised hedging opportunities more accurately compared to individual technical indicators, which ultimately led to higher achieved hedging levels. / MCom. (Risk management), North-West University, Potchefstroom Campus, 2014
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Timing a hedge decision : the development of a composite technical indicator for white maize / Susari Marthina GeldenhuysGeldenhuys, Susari Marthina January 2013 (has links)
The South African white maize market is considered to be significantly more volatile than any other agricultural product traded on the South African Futures Exchange (SAFEX). This accentuates the need to effectively manage price risk, by means of hedging, to ensure a more profitable and sustainable maize production sector (Geyser, 2013:39; Jordaan, Grové, Jooste, A. & Jooste, Z.G., 2007:320). However, hedging at lower price levels might result in significant variation margins or costly buy–outs in order to fulfil the contract obligations. This challenge is addressed in this study by making use of technical analysis, focusing on the development of a practical and applicable composite technical indicator with the purpose of improving the timing of price risk management decisions identified by individual technical indicators. This may ultimately assist a producer in achieving a higher average hedge level compared to popular individual technical indicators.
The process of constructing a composite indicator was commenced by examining the prevailing tendency of the market. By making use of the Directional Movement Index (DMI), as identified in the literature study, the market was found to continually shift between trending prices (prices moving either upwards or downwards) and prices trading sideways. Consequently, implementing only a leading (statistically more suitable for trading markets) or lagging (statistically more suitable for trending markets) technical indicator may generate false sell signals, as demonstrated by the application of these technical indicators in the white maize market. This substantiated the motivation for compiling a composite indicator that takes both leading and lagging indicators into account to more accurately identify hedging opportunities. The composite indicator made use of the Relative Strength Index (RSI) and Stochastic oscillator as leading indicators, and the Exponential Moving Average (EMA) and Moving Average Convergence Divergence (MACD) as lagging indicators. The results validated the applicability of such a composite indicator, as the composite indicator outperformed the individual technical indicators in the white maize market. The composite indicator achieved the highest average hedge level, the lowest average sell signals generated over the entire period, as well as the highest average hedge level as a percentage of the maximum price over the entire period. Hence, the composite indicator recognised hedging opportunities more accurately compared to individual technical indicators, which ultimately led to higher achieved hedging levels. / MCom. (Risk management), North-West University, Potchefstroom Campus, 2014
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Modelling the evolution of pulsar wind nebulae / Michael Johannes VorsterVorster, Michael Johannes January 2014 (has links)
This study focusses on modelling important aspects of the evolution of pulsar wind nebulae
using two different approaches. The first uses a hydrodynamic model to simulate the morphological
evolution of a spherically-symmetric composite supernova remnant that is expanding
into a homogeneous interstellar medium. In order to extend this model, a magnetic field is
included in a kinematic fashion, implying that the reaction of the fluid on the magnetic field
is taken into account, while neglecting any counter-reaction of the field on the fluid. This approach
is valid provided that the ratio of electromagnetic to particle energy in the nebula is
small, or equivalently, for a large plasma β environment. This model therefore allows one to
not only calculate the evolution of the convection velocity but also, for example, the evolution
of the average magnetic field.
The second part of this study focusses on calculating the evolution of the energy spectra of
the particles in the nebula using a number of particle evolution models. The first of these is
a spatially independent temporal evolution model, similar to the models that can be found
in the literature. While spatially independent models are useful, a large part of this study
is devoted to developing spatially dependent models based on the Fokker-Planck transport
equation. Two such models are developed, the first being a spherically-symmetric model that
includes the processes of convection, diffusion, adiabatic losses, as well as the non-thermal
energy loss processes of synchrotron radiation and inverse Compton scattering. As the magnetic
field geometry can lead to the additional transport process of drift, the previous model is
extended to an axisymmetric geometry, thereby allowing one to also include this process. / PhD (Space Physics), North-West University, Potchefstroom Campus, 2014
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Modelling the evolution of pulsar wind nebulae / Michael Johannes VorsterVorster, Michael Johannes January 2014 (has links)
This study focusses on modelling important aspects of the evolution of pulsar wind nebulae
using two different approaches. The first uses a hydrodynamic model to simulate the morphological
evolution of a spherically-symmetric composite supernova remnant that is expanding
into a homogeneous interstellar medium. In order to extend this model, a magnetic field is
included in a kinematic fashion, implying that the reaction of the fluid on the magnetic field
is taken into account, while neglecting any counter-reaction of the field on the fluid. This approach
is valid provided that the ratio of electromagnetic to particle energy in the nebula is
small, or equivalently, for a large plasma β environment. This model therefore allows one to
not only calculate the evolution of the convection velocity but also, for example, the evolution
of the average magnetic field.
The second part of this study focusses on calculating the evolution of the energy spectra of
the particles in the nebula using a number of particle evolution models. The first of these is
a spatially independent temporal evolution model, similar to the models that can be found
in the literature. While spatially independent models are useful, a large part of this study
is devoted to developing spatially dependent models based on the Fokker-Planck transport
equation. Two such models are developed, the first being a spherically-symmetric model that
includes the processes of convection, diffusion, adiabatic losses, as well as the non-thermal
energy loss processes of synchrotron radiation and inverse Compton scattering. As the magnetic
field geometry can lead to the additional transport process of drift, the previous model is
extended to an axisymmetric geometry, thereby allowing one to also include this process. / PhD (Space Physics), North-West University, Potchefstroom Campus, 2014
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