No / Pure anhydrous polymorphs of carbamazepine were prepared by solution-enhanced dispersion with supercritical fluids (SEDSTM). Crystallization of the polymorphs was studied. Mechanisms are proposed that consider the thermodynamics of carbamazepine, supersaturation in the SEDSTM process, and the binary phase equilibria of organic solvents and the carbon dioxide antisolvent. -Carbamazepine was crystallized at high supersaturations and low temperatures, -carbamazepine crystallized from a methanol-carbon dioxide phase split, and -carbamazepine crystallized via nucleation at high temperatures and low supersaturation.

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.

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 ¿m 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. / Egyptian Ministry of Higher Education

Magister Scientiae - MSc / We determine the stellar mass of star forming galaxies in the X-ray luminous cluster MS 0451.6-0305 at z ∼ 0.54. The stellar masses are estimated from fitting model spectral energy distributions (SEDs) to deep, optical UBRIz observations obtained from WIYN 3.5m telescope and public NIR K-band image from Palomar Observatory telescope. The model SEDs are based on the stellar population synthesis (SPS) model of Bruzual & Charlot (2003) and Conroy et al. (2009) that span a wide range of age, star formation history, Initial Mass Function (IMF), metallicity and dust content. We measure stellar masses for galaxies down to M∗∼2×10⁸M(.) We find a tight correlation between stellar masses derived from the two SPSs. We compare the derived stellar masses to the dynamical masses for a set of 25 star forming galaxies. The dynamical masses are derived from high resolution, spectroscopic observations of emission lines from the DEIMOS spectrograph on the Keck telescope. A strong correlation is seen between the dynamical and stellar mass for the galaxies; and the star forming galaxies show fairly constant ratio between stellar and dynamical mass. When comparing to the field sample of Guzm ́an et al. (2003) of luminous compact blue galaxies, we see an excess of low mass galaxies in the cluster. / South Africa

<p>The main aim of the thesis was to explore the potential of supercritical fluid (SF) techniques in the field of drug delivery. In particular, the relatively recently developed solution-enhanced dispersion by supercritical fluids (SEDS) technology has been employed in the preparation of particles/powders. </p><p>The manufacturing, stability and bioavailability of a dosage form strongly depend on the physicochemical properties of the formulation particles. For example, dry powder inhalation (DPI) for administering drugs to the respiratory tract require particles in a narrow size range (1-5 μm) to be effective. The identification of polymorphs and control of purity are also important issues since the physicochemical properties and therapeutic effects of the alternative forms of a drug may differ substantially. Solvent-based traditional crystallisation processes provide the product that may require further down-stream processing to obtain particles for advanced drug delivery applications. This can result in unwanted changes in the physicochemical properties of the particles and thus affect the performance of the dosage form. SF processing has addressed many of the challenges in particle formation research. Among several SF technologies developed for particle processing over the last decade, the SEDS process with its specially designed co-axial nozzle with mixing chamber has resulted in improved control over the particle formation process. Carbon dioxide (CO₂) was used as the SF, because it has low critical points and is non-toxic, non-flammable and relatively inexpensive. </p><p>The initial part of the thesis concerns the formation of particles of model drugs such as hydrocortisone, budesonide and flunisolide using SEDS technology and the determination of the influence of processing conditions and solvents on particle characteristics such as size, shape and crystal structure. Particles of model drugs of differing shapes in a size range suitable for inhalation delivery were prepared. In the process, two new polymorphic forms of flunisolide were identified. This was the first report of SEDS technology being shown as a polymorph-screening tool. The remainder of the thesis deals with the development of SEDS technology for precipitating therapeutic proteins such as recombinant human growth hormone (hGH) from aqueous solutions. Powders of hGH were precipitated using SEDS without significant changes in the chemical or physical stability of the protein. The addition of sucrose to hGH in the feed solution promoted precipitation and minimised the detrimental effects of the solvent and/or the process on the physical aggregation of the protein. </p><p>In conclusion, this thesis highlights the applicability of the SEDS process in drug delivery research and advances general understanding of the particle formation phenomenon. The SEDS process may also prove to be a potential alternative technology for the precipitation of stable powders of therapeutic proteins.</p>

The main aim of the thesis was to explore the potential of supercritical fluid (SF) techniques in the field of drug delivery. In particular, the relatively recently developed solution-enhanced dispersion by supercritical fluids (SEDS) technology has been employed in the preparation of particles/powders. The manufacturing, stability and bioavailability of a dosage form strongly depend on the physicochemical properties of the formulation particles. For example, dry powder inhalation (DPI) for administering drugs to the respiratory tract require particles in a narrow size range (1-5 μm) to be effective. The identification of polymorphs and control of purity are also important issues since the physicochemical properties and therapeutic effects of the alternative forms of a drug may differ substantially. Solvent-based traditional crystallisation processes provide the product that may require further down-stream processing to obtain particles for advanced drug delivery applications. This can result in unwanted changes in the physicochemical properties of the particles and thus affect the performance of the dosage form. SF processing has addressed many of the challenges in particle formation research. Among several SF technologies developed for particle processing over the last decade, the SEDS process with its specially designed co-axial nozzle with mixing chamber has resulted in improved control over the particle formation process. Carbon dioxide (CO2) was used as the SF, because it has low critical points and is non-toxic, non-flammable and relatively inexpensive. The initial part of the thesis concerns the formation of particles of model drugs such as hydrocortisone, budesonide and flunisolide using SEDS technology and the determination of the influence of processing conditions and solvents on particle characteristics such as size, shape and crystal structure. Particles of model drugs of differing shapes in a size range suitable for inhalation delivery were prepared. In the process, two new polymorphic forms of flunisolide were identified. This was the first report of SEDS technology being shown as a polymorph-screening tool. The remainder of the thesis deals with the development of SEDS technology for precipitating therapeutic proteins such as recombinant human growth hormone (hGH) from aqueous solutions. Powders of hGH were precipitated using SEDS without significant changes in the chemical or physical stability of the protein. The addition of sucrose to hGH in the feed solution promoted precipitation and minimised the detrimental effects of the solvent and/or the process on the physical aggregation of the protein. In conclusion, this thesis highlights the applicability of the SEDS process in drug delivery research and advances general understanding of the particle formation phenomenon. The SEDS process may also prove to be a potential alternative technology for the precipitation of stable powders of therapeutic proteins.