The aim of this work is to study the in-vitro aerodynamic performance of a new inhaled theophylline formulation prepared by supercritical fluids technique. For the analysis of the output from the in-vitro tests (and further in-vivo tests) a new, fast, sensitive high performance liquid chromatographic (HPLC) method was developed and validated for the determination of theophylline and other related derivatives in aqueous and urine samples using new packing materials (monolithic columns). These columns achieve efficient separation under lower backpressure and shorter time comparing to other traditionally or newly introduced C18 columns. Solution enhanced dispersion by supercritical fluid (SEDS) process has been applied for the production of anhydrous theophylline as pure crystals in the range 2-5 μm to be used as new inhaled dry powder formulation for asthma. Fifteen theophylline samples have been prepared under different experimental conditions. The drug produced by this method has been subject to a number of solid-phase analytical procedures designed to establish the crystal structure [X-ray powder diffraction (XRPD)], the structure and conformation [(FTIR), Fourier-transform Raman spectroscopy (FT-Raman)], and the morphology and particle size [scanning electron microscope (SEM)]. While, thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC) have been used to monitor any phase transition or polymorphic changes after processing. All these analytical techniques gave a satisfactory indication of the solid-state chemistry of the processed particles and assess the development of new inhalation product. The performance of inhaled SEDS theophylline with or without a carrier was evaluated using the developed HPLC method. Three samples having different particle sizes were selected out of the prepared powders by SEDS technique to be tested. The dose sampling unit and the Anderson Cascade Impactor were used to determine the in-vitro emitted dose and the deposition profiles of SEDS samples, respectively. The effect of different inhalation flows was studied using two different flows 28.3, and 60 L min-1 with 4 L inhalation volume. Different DPI devices were investigated in this study; Easyhaler® and Spinhaler®. The particle size has an important effect on the aerodynamic behaviour and deposition profile of inhaled drug, the smaller the particles the greater the total lung deposition. The presence of a carrier improves the respirable fraction for all the tested formulations.

No description available.

No description available.

Background: Tailings dam workers are exposed to tailings dust that has a potential health risk due to the element contents in the dust. The extent of exposure of tailings dam workers is unknown. Consequently, the elements, level of exposure, the potential adverse effects to health, compliance to legislative requirements and the efficiency of the current control measures were investigated. Design and Method: During the trials, 69 personal dust samples were collected during three full production shifts from tailings dam workers in three different tailings dam environments. The field filters were weighed to calculate the total dust concentrations. Bulk samples and field filters were analysed using the 32-element and particle size distribution scans. The between-dam, between-days and between-group variances were determined to assess the changes in exposure levels. Results: The tailings dam workers were not overexposed to tailings dust. Mean exposures were below the OEL for PNOC, measuring 0,124 mg/m3 (TD 1) 0,366 mg/m3 (TD 2) and 2,956 mg/m3 (TD 3). Three outliers in the data were present in TD 3 and exceeded the action level for PNOC. A major part of the particle size distribution consisted of inhalable sizes (>I0 μm). Cyclone tailings dams have smaller particle sizes than spigot tailings dams, though 85% of the particles in all tailings dams were larger than 10 μm. Some elements identified in the dust have potential respiratory health effects. No significant differences existed between the three tailings dams regarding tailings dust concentrations (p=0,527 on 5% significant level and p=0,292 on 10% significant level). There was, however, a significant difference on a 5% significant level between the days (p=0,003 and p=0,006). The workers on the cyclone tailings dams had smaller exposures than workers on the spigot tailings dams, and the pipeline labourers were more exposed than the mudguards. The tailings dams did comply with legislative control measures. However, washing facilities for the cleaning of overalls due to elements in the dust, such as nickel, chromium and manganese need to be considered. Workers need to be educated in work practices and procedures, personal hygiene and symptoms that can be experienced after exposure. Engineering control measures such as water sprayers covering the entire tailings dam, the use of fixed or temporary windscreens in the area where work is done and covering of the roads on the tailings dam with gravel or water spray can be considered as dust suppressant controls. Conclusion: The study met the issues set out in chapter 1, hypotheses were rejected and accepted and future studies were suggested. / Thesis (M.Sc. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2007.

Excipients are used in pharmaceutical formulations as fillers and drug carriers. Their successful function is inextricably linked to their physicochemical properties and, in turn, these properties are directly related to their structure. This thesis is concerned with the structural and spectroscopic characterisation of a selection of excipients by powder and single crystal X-ray diffraction, Raman and IR spectroscopy and MASNMR and an investigation of their stability as a function of temperature, humidity and particle size. As well as being a well-known excipient used in the pharmaceutical industry, lactose is also a common food additive. The diverse usage of lactose has led to a wealth of contradictory information relating to both structure and properties of this material. The first part of experimental work in this thesis identifies the four real lactose polymorphs; the naturally occurring a-lactose monohydrate; the anhydrous stable form of a-lactose; the hygroscopic unstable form of a-lactose; and the anomeric equivalent, p-lactose using powder X-ray diffraction. The work shows that anhydrous lactose formed by solvent dehydration often termed aM is simply the anhydrous stable form of a-lactose formed via a different route. Simple methods for discerning between the polymorphs using standard laboratory equipment are suggested. IlC MASNMR data were collected on all four forms of lactose for the first time and illustrate key differences between the four structures. Single crystal data were successfully collected on the a-lactose monohydrate and refinement carried at low temperature to determine the hydrogen bonded arrangement for the first time. Rietveld refmement of the hygroscopic unstable form of a-lactose using in-situ temperature resolved X-ray diffraction has shown that the hygroscopic form can be produced as a single phase. Refinement of Plactose using the Rietveld method has shown that powder diffraction data were comparable with single crystal data, with respect to structure refinement but attempts at both crystallisation and refinement of the stable anhydrous a-lactose polymorph were unsuccessful due to the complexity of the structure. Powder X-ray diffraction analysis was shown to be an effective tool in the quantification of mixed phase lactose samples with respect to both mixed phase stable anhydrous a-lactose and a-lactose monohydrate; and mixed p-Iactose and a-lactose monohydrate samples. The accuracy of the technique was determined to be at least 5%. Quantification was carried out using relative intensities of a well resolved unique reflection for each phase within the system. Dehydration techniques applied to lactose were applied to other hydrated pharmaceutical sugars; trehalose dihydrate and raffmose pentabydrate. Solid state techniques; powder X-ray diffraction, Raman and IR spectroscopy; showed that discrimination of other sugar hydrates became more complex with increasing levels of hydration.

Master of Science / Department of Grain Science and Industry / Charles R Stark / The uniformity of a feed mixture is determined from the coefficient of variation (CV) of ten samples in a single batch of feed. The feed industry standard is a %CV of less than 10 using a single source tracer such as salt, trace minerals or iron filings. The uniformity of mix can be affected by many factors including ingredient properties, equipment design, mix time, sampling method, sample preparation and overall precision of method. The objectives of this thesis were to verify the chloride ion test by the Quantab® chloride titrator method and to determine the effect of extended mixing time, salt particle size, sample preparation, wet mix time, spray condition, application time of the liquid addition, percent liquid addition and mixer type on the uniformity of mix. The first experiment evaluated the effect of water temperature, technician, extraction time, dissolution time on the chloride ion test by the Quantab® chloride titrator method. The salt concentration was significantly affected by water temperature and dissolution time. The results of Experiment 1 demonstrated the 60ºC water temperature and the 30 s extraction time by stirring followed by immediately placing the strip into the solution after extraction should be used for the Quantab® chloride titrator method. The second experiment evaluated the effect of extended mix time, particle size of salt and sample preparation on the %CV. The extended mix time did not result in segregation (P > 0.30). However, particle size of the salt and sample preparation significantly affected the uniformity of mix. The results of Experiment 2 indicated that the extended mix time of up to 60 minutes did not increase the %CV of the feed; the particle size of the salt used in the uniformity of mix test can significantly change the results of the test; and grinding the sample prior to analysis improved the precision of the Quantab® chloride titrator method when coarse salt is used in the manufacturing process. The third experiment evaluated the effect of wet mix time and the timing of the liquid addition using different spray conditions on the %CV. The wet mix time significantly changed the %CV of the mixture (P = 0.0057). The use of a spray nozzle had no effect on the %CV of the feed mixture when a 1.14% of a 23% saline solution was sprayed on to the feed (P = 0.7435). The results of Experiment 3 indicated the wet mix time had a greater influence on the uniformity of mix than the type of nozzle used to apply the liquid; and the shorter liquid application time allowed more time for the mechanical shear of the ribbons and paddles to break up the agglomerated wet particles and distribute them throughout the feed mixture when the total time of the liquid addition plus wet mix time was fixed. The fourth experiment evaluated the effect of different percent liquid addition, application time and mixer type with different wet mix times on the uniformity of mix. The %CV of feed mixed using a fixed wet mix time setting did not change when the percent liquid addition was increased, while the %CV of the feed mixed using a fixed total liquid mix time setting increased when increasing the percent liquid addition. The %CV of feed mixed with a ribbon mixer did not change when the liquid application time was decreased while the %CV of the feed mixed with a paddle mixer increased when decreasing the liquid application time. Differences were observed in the %CV based on the parameters of liquid cycle time, mixer type and mixer size. The results of Experiment 4 indicated the liquid addition time and the percent of liquid addition affected the uniformity of mix. The uniformity of liquid application should be tested with the highest percent liquid addition. Furthermore, application and wet mix times should be determined for each mixer type and size to establish the optimal batch cycle.

This study is dedicated to investigation of soot formed during combustion in diesel engine. Measurements were performed in a high speed direct injection optical diesel engine. Initially soot particle size, size distribution and soot volume fraction were investigated using time resolved laser induced incandescence (TR-LII) technique. For this study standard diesel fuel was used and measurements were performed for various injection timing and two different engine loads. Investigation showed that TR-LII is a powerful tool that can be used for characterization of in-cylinder soot in the engines. Subsequently TR-LII technique was developed to measure in-cylinder soot in two dimensional plane (planar laser induced incandescence PLII) and technique was combined with high speed imaging to investigate soot processes for ultra-low sulfur diesel (ULSD) and bio-fuel (RME). Two injection strategies of single and double injection were applied during these measurements. A high speed imaging technique was used to study the soot formation and oxidation during the combustion process within the cylinder and PLII was applied later in the stroke to study qualitatively the relative amount of un-oxidised soot that was left in the combustion chamber. In addition to PLII, TR-LII technique was used simultaneously to explore crank angle resolved variation of primary soot particle size and their size distribution during the expansion stroke. The same measurements were repeated for fuels with different composition investigating the relationship between the fuel properties and soot emission. Finally mathematical model for soot particle size and distribution width was modified by introducing assumption of multi-lognormal in-cylinder soot particle size distribution.

Cascade impactors, routinely used for in vitro particle size characterization of pharmaceutical aerosols, are calibrated using dilute, charge-neutralized, monodisperse aerosols. But pharmaceutical aerosols are known to generate concentrated, inherently charged, polydisperse aerosol clouds. A computational model of the Andersen Cascade Impactor (ACI) suggested that the presence of charge on aerosol particles may influence their deposition within the ACI, but experimental validation of the model is warranted. This dissertation investigates the influence of electrostatic charge upon the deposition behavior of aerosols within cascade impactors, to address the impact of charge on particle size characterization. The influence of applied charge upon the deposition pattern and aerodynamic particle size distribution (APSD) of commercially available pressurized metered dose inhalers (pMDIs) within the Electrical Low Pressure Impactor (ELPI) was examined. Electrostatic properties were modified using an external voltage source in conjunction with the ELPI corona charger and observed to be dependent on the formulation and device packaging. Induced artificial charge on the aerosol particles influenced the deposition pattern within the impactor, but did not result in a significant change in the apparent APSD. An experimental apparatus capable of producing charge neutralized and charged aerosol, with targeted deposition on the CFD predicted ‘charge sensitive’ ACI stages, was developed. In vitro results were observed to be in partial agreement with the CFD predictions. While charge influenced the deposition pattern in the ACI with increased deposition observed in the charger and on the upper stages of the ACI, it did not influence the apparent APSD of the aerosol. Electrostatic charge effects on deposition behavior within cascade impactors were delineated with respect to space charge and image charge effects by investigating the influence of impactor grounding, particle size, stage coating and loading. While the deposition pattern within the ACI was influenced by charge, only stage coating and stage loading resulted in a small, significant difference in the apparent APSD, which may not be practically relevant due to the variability associated with in vitro aerosol testing. Similar trends were observed in the deposition behavior of charge neutralized and charged aerosol within an abbreviated ACI system compared to the full resolution ACI.

Master of Science / Department of Animal Sciences and Industry / Joe D. Hancock / Nine experiments were completed to evaluate the effects of feed manufacturing practices on milling characteristics of diets and growth performance and stomach morphology in pigs. In Exp. 1 and 2, reducing the particle size of sorghum from 800 to 400 μm improved (P < 0.04) efficiency of gain in finishing pigs by 5% but had negative effects on cost of milling and stomach morphology. In Exp. 3 and 4, finishing pigs fed diets with 10 mg/kg of ractopamine HCl, had improved (P < 0.05) ADG, G:F, HCW, dressing percentage, and percentage carcass lean. However, increasing mix time of the diet from 0 to 360 s did not affect (P > 0.06) the response of finishing pigs to ractopamine HCl. In Exp. 5 and 6, adding ground and cracked corn to a pelleted supplement for nursery pigs decreased (P < 0.01) growth performance compared to feeding a complete pellet. In Exp. 7, increasing the percentage of cracked corn in a diet for finishing pigs decreased development of stomach lesions but also had a generally negative effect on efficiency of gain. In Exp. 8, adding cracked corn to a pelleted supplement (as done for the nursery pigs) decreased milling costs and improved health of stomach tissue. But, G:F was decreased by 6% (P < 0.05) which will make this technology unattractive to swine producers. In our final experiment (Exp. 9), pigs fed pellets tended to have the greatest growth performance, pigs fed mash the worst, and pigs fed pellets for only part of the grow-finish phase fell in between. In conclusion, grinding sorghum-based diets for finishing pigs improved efficiency of growth but extensive mixing to maximize diet uniformity had no effect on growth performance or carcass measurements. Use of cracked corn in diets does decrease diet costs and improve stomach health in finishing pigs but feeding of complete pellets for the entire finishing period supports maximum rate and (or) efficiency of gain.

Master of Science / Department of Animal Sciences and Industry / Joel DeRouchey / Seven experiments using a total of 2,997 nursery and finishing pigs were used to determine the effects of: 1) dietary wheat middlings (midds), dried distillers grains with solubles (DDGS), and NE diet formulation on nursery pig growth performance; 2) corn particle size, complete diet grinding, and diet form on finishing pig growth performance, and carcass characteristics, and 3) particle size, complete diet grinding, and diet form on nursery pig growth. Experiments 1-4 evaluated dietary wheat middlings at levels of up to 20% of the diet for 7 to 23 kg pigs. Increasing dietary midds decreased growth performance but mainly when 10% of more was added. Balancing diets containing 10 or 20% midds on a NE basis had no significant effects on performance compared with not adjusting for NE of the diet. In Exp. 5, the effects of decreasing particle size, complete diet grinding, and diet form were evaluated on finishing pig growth performance, and carcass characteristics. Diet form × portion ground interactions existed for ADG, ADFI, and HCW as grinding the complete diet in meal form was detrimental to performance but advantageous to performance when diets were fed in pelleted form. Reducing the particle size of corn improved G:F and caloric efficiencies. Pelleting the diet improved ADG, G:F, caloric efficiencies, HCW, and loin depth. Experiment 6 evaluated varying particle sizes, diet form, and complete diet grinding on nursery pig growth performance. Pigs fed pelleted diets had improved ADG, G:F, and caloric efficiencies. Fine grinding corn or the complete diet with high by-products diet decreased ADG, ADFI, G:F, and final BW. Experiment 7 evaluated varying particle sizes of corn and DDGS, diet form, and complete diet grinding on nursery pig growth performance. Pigs fed finely ground corn had decreased ADFI when the diet was fed in pellet form and more severe reductions in ADFI when diets were fed in meal form resulting in a diet form × corn particle size interaction. Pigs fed pelleted diets had decreased ADG, ADFI, G:F and final BW, but improved caloric efficiencies. Finely grinding corn decreased ADG, and feeding DDGS decreased ADG, ADFI, and NE caloric efficiency.