Browsing by Subject "Liquid crystals"
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Item Effects of additives on the molecular-level behavior of disordered pharamceuticals(2020-12) Amponsah-Efah, KwekuAmorphous solid dispersions (ASDs) can improve the oral bioavailability of poorly water-soluble drugs. However, the physical instability of the amorphous form, denoted by the propensity to recrystallize, is a major barrier to the use of ASDs. The overarching goal of this thesis was to understand the mechanisms by which two major classes of additives – antiplasticizers (various polymers) and plasticizers (mainly glycerol) – affect the physical stability of amorphous formulations, in the dry solid form, as well as in aqueous solution. In the first project, we investigated the impact of the strength of drug–polymer interactions, on the dissolution performance of ASDs. With ketoconazole and three polymers as model compounds, we observed that the interactions that stabilize amorphous drugs in the solid state, can also be relevant and important in sustaining the level of supersaturation in aqueous solution. The second project explored the use of analytical ultracentrifugation as a novel technique for characterizing drug–polymer interactions in aqueous buffers. It was possible to quantify the “free” versus “bound” fractions of drug in aqueous solution, and to semi-quantitatively assess the impact of interactions on the dissolution performance of ASDs. The third and fourth projects evaluated the effects of glycerol on the molecular mobility and physical stability of amorphous itraconazole (ITZ), in the “solid” state. It is well-known that small molecule plasticizers, such as water or glycerol, increase the molecular mobility and accelerate the crystallization of amorphous drugs. In the case of amorphized ITZ, however, glycerol at low concentrations did not cause physical instability. Rather, the smectic state (one of the intermediate liquid-crystalline phases of ITZ) was selectively stabilized. The mechanism by which glycerol stabilized the smectic state was investigated with high resolution techniques (synchrotron diffractometry, differential and adiabatic scanning calorimetry, and spectroscopy). The results revealed that additives with fast dynamics, can drive weak first-order (or second-order) intermediate liquid-crystalline phase transitions, to strong first-order transitions, by a possible coupling of the additive concentration to the order parameter. We also demonstrated that the stabilized smectic state can perform the dual role of maintaining good physical stability while achieving adequate dissolution performance.Item Mesoscale models for soft layered materials: the role of curvatures in topological defect motion, flows and instabilities(2020-09) Vitral, EduardoCurvature driven phenomena in soft matter involves both complex geometry at small scales and anisotropies associated with material symmetries. In particular, the class of soft modulated materials present molecules that are organized in layers, so that material properties significantly vary between the direction normal to the layer and those of the layers. This is the case of smectic liquid crystals, which behave as a solid in the direction normal to the molecular layers, while each of their layers behave as a two-dimensional fluid. Under appropriate boundary conditions, smectic layers are known to bend and form focal conic defects, whose curvatures significantly increase in magnitude as the tip of the cone is approached. Intriguingly, experiments on smectic films presenting arrays of focal conics have shown that these materials undergo unexpected morphological transitions, which are not explained by classical local equilibrium thermodynamics. For example, annealing of focal conic domains can lead to conical pyramids, changing the sign of both mean and Gaussian curvatures and exposing smectic layers at the interface. In order to understand the role played by high order curvature terms on the stability and evolution of a smectic film interface, we propose a phase-field model for a smectic-isotropic system. Through an asymptotic analysis, we generalize the classical condition of local equilibrium, the Gibbs-Thomson equation, to include contributions from surface bending and torsion and a dependence on the layer orientation at the interface. Numerical results for a diffusive evolution of the interface reproduce the focal conic to conical pyramid transition in smectic films, and we show that such morphologies can be explained in light of the derived interface equations. We then generalize this model to include flows and to allow each phase to have a different density. We derive both a quasi-incompressible and a weakly compressible smectic-isotropic model from this approach, explaining their applicability and limitations. Finally, we investigate the role of flows and defect interactions in two-dimensional active smectics, known as the spiral defect chaos state in Rayleigh-Bénard convection.