Roxithromycin is a semi-synthetic, macrolide antibiotic, derived from erythromycin A. It acts as a bacteriostatic drug at low concentrations and a bactericidal drug at high concentrations. It binds to the 50S subunit of the 70S ribosome, which causes the reversible inhibition of RNA-dependent bacterial protein synthesis. It is well known that active pharmaceutical ingredients (APIs) may exist in numerous solid states. Differences in the solid state significantly influence the physical and chemical properties of an API. The in vivo performance of a dosage form will also be influenced by the solid state properties of a given pharmaceutical active. The amorphous characteristics of APIs have a significant impact on their performance and thus offer the potential for exciting new pharmaceuticals. Whilst amorphous forms of poorly soluble APIs are more soluble than their crystalline counterparts, they tend to be physically unstable, which makes their formulation into solid dosage forms quite challenging. Roxithromycin has only 50% oral bioavailability due to its poor aqueous solubility and for this reason, its potential for optimal therapeutic effect are limited. Poor solubility is thus an important obstacle in formulation development. During this study, amorphous forms of roxithromycin were prepared via quench cooling, and desolvation of chloroform- and ethyl acetate solvates. These amorphous forms were characterised by means of several techniques, whilst their solubilities and stabilities were also investigated. The outcomes of the solubility studies illustrated the complexity of this API and its amorphous forms with regards to their interactions with water. Solubility studies confirmed the superior solubility of the roxithromycin glass (prepared through quench cooling) and amorphous forms (desolvation of solvates) over the roxithromycin monohydrate in water. The solubility in water improved in the order of roxithromycin monohydrate < roxithromycin glass < roxithromycin glass powder < amorphous chloroform desolvate. The roxithromycin monohydrate, as well as the amorphous forms of roxithromycin demonstrated stability over a one-month period of exposure 40°C and relative humidity (RH) of 75%. The roxithromycin glass powder tended to revert to the more stable crystalline monohydrate after week 3 of stability testing. The roxithromycin glass at lower temperatures of 25°C and 30°C (both at 75% RH) tended to transform into the more crystalline form at week 4 of the study. These transformations were, however, not as significant as during the 40°C / 75% RH study. The conclusion could therefore be made that this transformation into the crystalline form was more temperature – than moisture dependant. At a higher temperature (at identical humidity conditions), the transformation into the crystalline form was much faster. Stability studies on the two roxithromycin desolvates were also performed in order to determine whether these amorphous forms, would differ, with regards to their stability, from the glass prepared through heating and cooling. It was determined that the desolvates were more stable than the roxithromycin glass. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2012

The effect of fluorine on the solubilities of Mn-columbite (MnNb2O6), Mn-tantalite (MnTa2O6), zircon (ZrSiO4) and hafnon (HfSiO4) were determined in highly fluxed, water-saturated haplogranitic melts at 800 to 1000 °C and 2000 bars. The melt corresponds to the intersection of the granite minimum with the albite-orthoclase tieline (Ab72Or28) in the quartz-albite-orthoclase system (Q-Ab-Or) due to the addition of P2O5 to the melt. The melt content of P2O5 is 1.7 wt. %, and also contains 1.1 and 2.02 wt. % of Li2O and B2O3, respectively. The composition of the starting glass represents the composition of melts from which rare-elements pegmatites crystallized. Up to 6 wt. % fluorine was added as AgF in order to keep the aluminum saturation index (ASI) of the melt constant. In an additional experiment F was added as AlF3 to make the glass peraluminous. The nominal ASI (molar Al/[Na+K]) of the melts is close to 1 and approximately 1.32 in peraluminous glasses, but if Li considered as an alkali, the ASI of the melts are alkaline (0.85) and subaluminous (1.04), respectively. The solubility products [MnO]*[Nb2O5] and [MnO]*[Ta2O5] are nearly independent of the F content of the melt, approximately 18.19 ± 1.2 and 43.65 ± 2.5 x10-4 KSP (mol2/kg2), respectively. By contrast, there is a positive dependence of zircon and hafnon solubilities on the fluorine content, which increases from 2.03 ± 0.03 x10-4 (mol/kg) ZrO2 and 4.04 ± 0.2 x10-4 (mol/kg) HfO2 for melts with 0 wt. % F to 3.81 ± 0.3 x10-4 (mol/kg) ZrO2 and 6.18 ± 0.04 x10-4 (mol/kg) HfO2 for melts with 8 wt. % F. Comparison of the data from this work and previous studies indicates that ASI of the melt seems to have a stronger effect than the contents of fluxing elements in the melt and the overall conclusion is that fluorine is less important (relative to melt compositions) than previously thought for the control on the behavior of high field strength elements in highly evolved granitic melts. Moreover, this study confirms that although Nb, Ta, Zr and Hf are all high field strength elements, Nb-Ta and Zr-Hf are complexed differently.

Most crude oils contain traces of vanadyl porphyrins within their asphaltene fraction. Although these metals are only present in trace quantities, they have a significant detrimental impact on crude oil processing units; therefore, their selective removal is highly desirable. The current work studied the interaction of these vanadyl porphyrins with asphaltenes using two approaches: 1) equilibrium solubility measurements of model porphyrins and 2) membrane diffusion measurements in dilute solution. Solubility measurements with model porphyrins showed that simple model porphyrins fit the operational definition for asphaltenes, exhibiting negligible solubility in n-heptane and orders of magnitude higher solubility in toluene. Measurement of the melting point properties enabled modeling of their solubility behaviour and showed that simple models incorporating solubility parameters (Regular solution and Flory-Huggins) were not capable of describing the observed behaviour. Diffusion measurements were done using model vanadyl porphyrins, asphaltenes, and petroporphyrins in toluene using a stirred diffusion cell equipped with ultrafiltration membranes (Ultracel YM and Anopore). The pore sizes were varied between 3-20 nm to retain aggregates while allowing free molecules to diffuse. The permeate was continuously monitored using in situ UV/Visible spectroscopy. These experiments determined that the size of the asphaltene aggregates at 1 g/L in toluene at 25C were in the range of 5-9 nm. An increase in temperature results in an increase in asphaltene mobility but does not reduce the size of the asphaltene structures below 5 nm. Likewise, a decrease in concentration to 0.1 g/L did not result in a decrease in size. It was also observed that the exclusion of a large portion of the total asphaltenes by pores < 5 nm eliminates the absorbance of visible light (>600 nm) indicating the presence of Rayleigh scattering for the aggregated species in solution. The petroporphyrins are larger than the model vanadyl porphyrins as indicated by pore hindrance effects within smaller pores. An increase in temperature results in an increase in petroporphyrin mobility, although decreasing the asphaltene concentration does not. The mobility of the vanadyl petroporphyrins is affected by the origin of the sample (Safaniya, Venezuela, Athabasca) and is therefore not universal. / Chemical Engineering

Pulmonary and oral drug administrations are usually the preferred methods of delivery of active pharmaceutical ingredients.Generally,pulmonary drug formulations are more attractive compared to oral formulations since they consist of micron-sized powders with high surface area thus having faster onset of action,as well as minimizing the drug dosage and side effects.Oral insulin formulations,if achievable,would provide an alternative to injectable insulin,as the common drawbacks of injectable insulin are the multiple daily injections and the possibility of skin infections at the injection site. In this study,the feasibility of using dense gas particle processing techniques known as the Aerosol Solvent Extraction System (ASES),Gas Anti-Solvent (GAS)and High-Pressure Media Milling (HPMM)for pharmaceutical processing was assessed.The ASEStechnique,utilizing dense ethane,was employed to prepare insulin-lactose formulations for pulmonary administration whilst the GAS and ASES techniques,utilizing dense CO2,were employed to prepare microencapsulated formulations containing insulin and Eudragit?? S100 for oral administration.Furthermore,the HPMM technique,utilizing dense hydrofluocarbon (HFC)134a/227ea,was employed to prepare suspension Metered Dose Inhaler (MDI)formulations containing budesonide and various surfactants. The Fine Particle Fraction (FPF)of processed insulin without the presence of lactose was found to be 44%.In other words,44% of processed insulin delivered to the impactor stages (excluding the throat and neck)has aerodynamic diameter of less than 5??m.With the addition of lactose as carrier,the FPFof the insulin-lactose (1:1w/w)formulation increased to 64%.The increase in FPFwas attributed to the lower density of lactose particles compared to that of insulin particles to produce an intimate mixture with enhanced powder flowability and aerodynamic performance. Proteins for oral delivery should ideally be formulated with acid-resistant polymer as a protective coating to protect against enzymatic degradation in the stomach.Eudragit?? S100,which is insoluble or almost impermeable at pH 1-4and soluble at pH 5-7,was used to prepare oral insulin formulations.The insulin release at pH 3was sustained by the Eudragit?? S100coating and the encapsulation efficiency of insulin??Eudragit?? S100formulations varied between 6% and 24% depending on the initial drug to polymer ratio. One of the major therapies utilizing metered dose inhaler formulations in the treatment of asthma has been studied using the HPMM process.The HPMM process has been demonstrated to be an efficient milling process for the enhancement of the physical stability and aerodynamic performance of budesonide in HFC-134a/227ea propellant formulations.No significant change in physical stability was observed in the formulations for 2 weeks.

The dissolution profile of orally delivered drugs can be controlled through the use of osmotically controlled drug delivery devices. The most commonly used device is the osmotic tablet, which is essentially a tablet core that is coated with a rate-limiting semipermeable membrane. The feasibility of applying a coating onto a tablet using dense gas techniques was studied. Two different coating materials, polymethymethacrylate (PMMA, Mw = 120,000 g/mol) and cellulose acetate (CA, 39.8 wt% acetyl content) were applied onto an 8 mm osmotic tablet core using the Gas Anti-solvent (GAS) process. For PMMA, the pressurisation rate, coating temperature and volumetric expansion of up to 250% had minimal effect on the coating quality. The concentration, solvent type and the use of polyethylene glycol (Mw = 200 g/mol) had a more pronounced effect on the coating. The coating process was optimised to apply a smooth and uniform coating with a 50 ??m thickness. For CA, the pressurisation rate and the coating temperature had little effect on the coating that was applied. The process was more sensitive to a change in the concentration of the solution and the volumetric expansion that was used. It was found that the concentration could not be increased too much without affecting the coating quality. A CA coating was applied onto a PMMA-coated tablet using the optimised conditions. The thickness in the tablet coating increased by 10 ??m. Dissolution tests of the uncoated and coated tablets were carried out. The CA coatings were found to be insufficient in limiting the rate of water entering the tablet and performed similarly to an uncoated tablet core. The PMMA coatings were found to limit the rate of delivery of the model drug. However, variations in the PMMA coatings resulted in an inconsistent delivery profile across batches. The tablets coated with both PMMA and CA had a delivery rate in between that of uncoated and PMMA-coated tablets, indicating that the application of the second coating had compromised the initial PMMA coating.

Very little is known about the hydrophobic proteins of psychrophiles and their roles in cold adaptation. In light of this situation, methods were developed to analyse the hydrophobic proteome (HPP) of the model psychrophilic archaeon Methanococcoides burtonii. Central to this analysis was a novel differential solubility fractionation procedure, which resulted in a significant increase in the efficiency of resolving the HPP. Over 50% of the detected proteins were not identified in previous whole cell extract analyses, and these underwent an intensive manual annotation process producing high quality functional assignments. Utilising the functional assignments, biological context analysis of the HPP was performed, revealing novel and often unique biology. The analysis acted as a platform for differential proteomics of the organism???s response to both temperature and substrate using stable isotope labelling. The results of which revealed that low temperature growth was associated with an increase in the abundance of surface and secreted proteins, and translation apparatus. Conversely, growth at a higher temperature was associated with an increase in the abundance of general protein folding machinery and indications of an oxidative stress response, emphasising that the temperature for maximum growth rate is stressful. Through investigation of the response of M. burtonii to substrate it was found that growth on methanol was stressful, and its low energy yield resulted in an increase in the abundance of energy conserving systems. The extracellular polymeric substance (EPS) and morphology of M. burtonii was also investigated with respect to both temperature and substrate, using a number of techniques in microscopy. It was found that the EPS was comprised of proteins, sugars and RNA, and that growth at different temperatures resulted in the production of EPS that displayed significantly different properties on dehydration, thus indicating compositional variation. When cells were grown on methanol they took on highly irregular shapes and had electron transparent inclusions. The observations from the ultrastructural analysis were contemplated with respect to the proteomic findings, revealing novel avenues of research. This study has highlighted the roles of hydrophobic proteins in cold adaptation biology, and the value of comprehensive proteomics for the examination of adaptation in microorganisms

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Thesis (M.S.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains ix, 123 p. : ill. (some col.) Includes abstract. Includes bibliographical references (p. 71-82).

Akademisk avhandling--Lund. / Extra t.p., with thesis statement, inserted. Bibliography: p. 10.

Thesis (M.S.)--University of Wisconsin--Madison, 1961. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaf 27).