In recent years, the use of self-associating block copolymer based drug delivery systems have attracted increasing attention as nanoscopic carriers for the encapsulation and the controlled delivery of water insoluble drugs. Currently, most of the drug formulations proceed by trial and error method with no distinct method to predict the right combination of block copolymers and drugs to give all the desired functional properties. This is simply because such drug delivery systems involve complex intermolecular interactions and geometric fitting of molecules of different shapes. So, in the context of block copolymer design process, quantification and prediction of the interactions between potential block copolymers and the target drug are of great importance. Computer simulations that can predict the level and type of interactions encountered in drug/block copolymer pairs will enable researchers to make educated decisions on choosing a particular polymeric carrier for a given drug, avoiding time consuming and expensive trial and error based formulation experiments. In the present thesis, we reported the use of molecular dynamics (MD) simulation to predict the solubility of sets of hydrophobic drug molecules having different spatial distribution of hydrogen bond forming moieties in a series of micelle-forming PEO-b-PCL block copolymers with and without functionalized PCL blocks. The solubility predictions based on the MD results were then compared with those obtained from the solubility experiments and those obtained by the commonly used group contribution method (GCM). MD analysis techniques like radial distribution functions provided useful atomistic details to understand the molecular origin of miscibility and/or immiscibility observed between drugs and di-block copolymers. Based on the evidence of reported work, intermolecular specific interactions, intra-molecular interactions, local molecular packing, and stereochemistry of the hydrophobic block all play important roles in inducing miscibility between drugs and block copolymers. Additionally, not only the architecture of block copolymers but also the molecular characteristics of drug molecules, e.g., spatial distributions of hydrogen bond donors and acceptors on their molecules can affect the miscibility characteristics of binary mixtures. Depending on the groups present on drugs and block copolymers, any of the above factors can play vital role in the process of favouring encapsulation. The understanding of relative contributions of these interactions can help us to customize the performance of drug carriers by engineering the structure of block copolymers. / Chemical Engineering

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The knowledge of the phase behaviour of heavy oils and bitumen is important in order to understand the phenomenon of coke formation. Computation of their phase behaviour, using an equation of state, faces problems due to their complex composition. Hence n-alkane binaries of polyaromatic hydrocarbons are used to approximate the phase behaviour of heavy oils and bitumen. Appropriate values of binary interaction parameters are required for an equation of state to predict the correct phase behaviour of these model binary fluids. This thesis deals with fitting of the binary interaction parameter for the Peng-Robinson equation of state using landmarks in the binary phase space such as K- and L-points. A K- or an L-point is a point in the phase space where two phases become critical in the presence of another phase in equilibrium. An algorithm to calculate K- and L-points using an equation of state was developed. The variation of calculated K- and L-points with respect to the binary interaction parameter was studied and the results were compared with the experimental data in the literature. The interaction parameter was then fitted using the best match of experimental results with the computed ones. The binary interaction parameter fitted using a K- or an L-point was then used to predict the P-T projection of the binary system in phase space. Also, the qualitative effect of the binary interaction parameter on the P-T projection was studied. A numerical and thermodynamic study of the algorithm was done. Numerical issues like the initial guesses, convergence criterion and numerical techniques were studied and the thermodynamic constraints in the generalization of the algorithm are discussed. It was observed that the binary interaction parameter not only affects the location of K- and L-points in the phase space but also affects the calculation procedure of K- and L-points. Along with the propane binaries of polyaromatic hydrocarbons, K- and L-points were also calculated for systems like methane binaries of higher n-alkanes and the ethane + ethanol binary. In the case of the ethane + ethanol system, K- and L-points, matching the experimental results were calculated with different values of the binary interaction parameter. But the Peng-Robinson equation of state was unable to predict the correct type of phase behaviour using any value of the binary interaction parameter. The Peng-Robinson equation of state was able to predict the correct type of phase behaviour with the binary interaction parameter, fitted using K- and/or L-points for methane + n-alkane systems. The systems studied were the methane binaries of n-pentane, n-hexane and n-heptane. For the propane binaries of polyaromatic hydrocarbons, no value of the binary interaction parameter was able to predict the K-point with a good accuracy. The binary interaction parameter which gave the best possible results for a K-point failed to predict the correct type of phase behaviour. The binary interaction parameter fitted using the P-T projection enabled the Peng-Robinson equation of state to give a qualitative match for the high pressure complex phase behaviour of these systems. Solid phase equilibria were not taken into consideration.

The knowledge of the phase behaviour of heavy oils and bitumen is important in order to understand the phenomenon of coke formation. Computation of their phase behaviour, using an equation of state, faces problems due to their complex composition. Hence n-alkane binaries of polyaromatic hydrocarbons are used to approximate the phase behaviour of heavy oils and bitumen. Appropriate values of binary interaction parameters are required for an equation of state to predict the correct phase behaviour of these model binary fluids. This thesis deals with fitting of the binary interaction parameter for the Peng-Robinson equation of state using landmarks in the binary phase space such as K- and L-points. A K- or an L-point is a point in the phase space where two phases become critical in the presence of another phase in equilibrium. An algorithm to calculate K- and L-points using an equation of state was developed. The variation of calculated K- and L-points with respect to the binary interaction parameter was studied and the results were compared with the experimental data in the literature. The interaction parameter was then fitted using the best match of experimental results with the computed ones. The binary interaction parameter fitted using a K- or an L-point was then used to predict the P-T projection of the binary system in phase space. Also, the qualitative effect of the binary interaction parameter on the P-T projection was studied. A numerical and thermodynamic study of the algorithm was done. Numerical issues like the initial guesses, convergence criterion and numerical techniques were studied and the thermodynamic constraints in the generalization of the algorithm are discussed. It was observed that the binary interaction parameter not only affects the location of K- and L-points in the phase space but also affects the calculation procedure of K- and L-points. Along with the propane binaries of polyaromatic hydrocarbons, K- and L-points were also calculated for systems like methane binaries of higher n-alkanes and the ethane + ethanol binary. In the case of the ethane + ethanol system, K- and L-points, matching the experimental results were calculated with different values of the binary interaction parameter. But the Peng-Robinson equation of state was unable to predict the correct type of phase behaviour using any value of the binary interaction parameter. The Peng-Robinson equation of state was able to predict the correct type of phase behaviour with the binary interaction parameter, fitted using K- and/or L-points for methane + n-alkane systems. The systems studied were the methane binaries of n-pentane, n-hexane and n-heptane. For the propane binaries of polyaromatic hydrocarbons, no value of the binary interaction parameter was able to predict the K-point with a good accuracy. The binary interaction parameter which gave the best possible results for a K-point failed to predict the correct type of phase behaviour. The binary interaction parameter fitted using the P-T projection enabled the Peng-Robinson equation of state to give a qualitative match for the high pressure complex phase behaviour of these systems. Solid phase equilibria were not taken into consideration.

The goal of this project was to develop a non-toxic amphiphilic diblock copolymer nanoparticulate drug delivery system that will solubilize paclitaxel (PTX) and retain the drug in plasma. Methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (MePEG-b-PCL) diblock copolymers loaded with PTX were characterized and their physicochemical properties were correlated with their performance as nanoparticulate drug delivery systems. A series of MePEG-b-PCL was synthesized with PCL blocks ranging from 2-104 repeat units and MePEG blocks of 17, 44 or 114 repeat units. All copolymers were water soluble and formed micelles except MePEG₁₁₄-b-PCL₁₀₄, which was water insoluble and formed nanospheres. Investigation of the effects of block length on the physicochemical properties of the nanoparticles was used to select appropriate copolymers for development as PTX nanoparticles. The critical micelle concentration, pyrene partition coefficient and diameter of nanoparticles were found to be dependent on the PCL block length. Copolymers based on a MePEG molecular weight of 750 g/mol were found to have temperature dependent phase behavior. Relationships between the concentration of micellized drug and the compatibility between the drug and core-forming block, as determined by the Flory-Huggins interaction parameter, and PCL block length were developed. Increases in the compatibility between PCL and the drug, as well as longer PCL block lengths resulted in increased drug solubilization. The physicochemical properties and drug delivery performance characteristics of MePEG₁₁₄-b-PCL₁₉ micelles and MePEG₁₁₄-b-PCL₁₀₄ nanospheres were compared. Nanospheres were larger, had a more viscous core, solubilized more PTX and released it slower, compared to micelles. No difference was seen in the hemocompatibility of the nanoparticles as assessed by plasma coagulation time and erythrocyte hemolysis. Micellar PTX had an in vitro plasma distribution similar to free drug. The majority of micellar PTX associated with the lipoprotein deficient plasma fraction (LPDP). In contrast, nanospheres were capable of retaining more of the encapsulated drug with significantly less PTX partitioning into the LPDP fraction. In conclusion, although both micelles and nanospheres were capable of solubilizing PTX and were hemocompatible, PTX nanospheres may offer the advantage of prolonged blood circulation, based on the in vitro plasma distribution data, which showed that nanospheres retained PTX more effectively.

The goal of this project was to develop a non-toxic amphiphilic diblock copolymer nanoparticulate drug delivery system that will solubilize paclitaxel (PTX) and retain the drug in plasma. Methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (MePEG-b-PCL) diblock copolymers loaded with PTX were characterized and their physicochemical properties were correlated with their performance as nanoparticulate drug delivery systems. A series of MePEG-b-PCL was synthesized with PCL blocks ranging from 2-104 repeat units and MePEG blocks of 17, 44 or 114 repeat units. All copolymers were water soluble and formed micelles except MePEG₁₁₄-b-PCL₁₀₄, which was water insoluble and formed nanospheres. Investigation of the effects of block length on the physicochemical properties of the nanoparticles was used to select appropriate copolymers for development as PTX nanoparticles. The critical micelle concentration, pyrene partition coefficient and diameter of nanoparticles were found to be dependent on the PCL block length. Copolymers based on a MePEG molecular weight of 750 g/mol were found to have temperature dependent phase behavior. Relationships between the concentration of micellized drug and the compatibility between the drug and core-forming block, as determined by the Flory-Huggins interaction parameter, and PCL block length were developed. Increases in the compatibility between PCL and the drug, as well as longer PCL block lengths resulted in increased drug solubilization. The physicochemical properties and drug delivery performance characteristics of MePEG₁₁₄-b-PCL₁₉ micelles and MePEG₁₁₄-b-PCL₁₀₄ nanospheres were compared. Nanospheres were larger, had a more viscous core, solubilized more PTX and released it slower, compared to micelles. No difference was seen in the hemocompatibility of the nanoparticles as assessed by plasma coagulation time and erythrocyte hemolysis. Micellar PTX had an in vitro plasma distribution similar to free drug. The majority of micellar PTX associated with the lipoprotein deficient plasma fraction (LPDP). In contrast, nanospheres were capable of retaining more of the encapsulated drug with significantly less PTX partitioning into the LPDP fraction. In conclusion, although both micelles and nanospheres were capable of solubilizing PTX and were hemocompatible, PTX nanospheres may offer the advantage of prolonged blood circulation, based on the in vitro plasma distribution data, which showed that nanospheres retained PTX more effectively.

The goal of this project was to develop a non-toxic amphiphilic diblock copolymer nanoparticulate drug delivery system that will solubilize paclitaxel (PTX) and retain the drug in plasma. Methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (MePEG-b-PCL) diblock copolymers loaded with PTX were characterized and their physicochemical properties were correlated with their performance as nanoparticulate drug delivery systems. A series of MePEG-b-PCL was synthesized with PCL blocks ranging from 2-104 repeat units and MePEG blocks of 17, 44 or 114 repeat units. All copolymers were water soluble and formed micelles except MePEG₁₁₄-b-PCL₁₀₄, which was water insoluble and formed nanospheres. Investigation of the effects of block length on the physicochemical properties of the nanoparticles was used to select appropriate copolymers for development as PTX nanoparticles. The critical micelle concentration, pyrene partition coefficient and diameter of nanoparticles were found to be dependent on the PCL block length. Copolymers based on a MePEG molecular weight of 750 g/mol were found to have temperature dependent phase behavior. Relationships between the concentration of micellized drug and the compatibility between the drug and core-forming block, as determined by the Flory-Huggins interaction parameter, and PCL block length were developed. Increases in the compatibility between PCL and the drug, as well as longer PCL block lengths resulted in increased drug solubilization. The physicochemical properties and drug delivery performance characteristics of MePEG₁₁₄-b-PCL₁₉ micelles and MePEG₁₁₄-b-PCL₁₀₄ nanospheres were compared. Nanospheres were larger, had a more viscous core, solubilized more PTX and released it slower, compared to micelles. No difference was seen in the hemocompatibility of the nanoparticles as assessed by plasma coagulation time and erythrocyte hemolysis. Micellar PTX had an in vitro plasma distribution similar to free drug. The majority of micellar PTX associated with the lipoprotein deficient plasma fraction (LPDP). In contrast, nanospheres were capable of retaining more of the encapsulated drug with significantly less PTX partitioning into the LPDP fraction. In conclusion, although both micelles and nanospheres were capable of solubilizing PTX and were hemocompatible, PTX nanospheres may offer the advantage of prolonged blood circulation, based on the in vitro plasma distribution data, which showed that nanospheres retained PTX more effectively. / Pharmaceutical Sciences, Faculty of / Graduate

The purpose of this study was to investigate the fundamental characteristics of a chelating surfactant in terms of solution behaviour, chelation of divalent metal ions, and interaction in mixtures with different foaming agents and divalent metal ion, as well as examining its prospects in some practical applications. Chelating surfactants are functional molecules, with both surface active and chelating properties, which are water soluble and therefore suitable for chelation in many aqueous environments. The dual functionality offers the possibility to recover the chelating surfactant as well as the metals. The DTPA (diethylenetriaminepentaacetic acid)-based chelating surfactant 4-C12-DTPA (2-dodecyldiethylenetriaminepentaacetic acid) was synthesized at Mid Sweden University. In the absence of metal ions, all eight donor atoms in the headgroup of 4-C12-DTPA are titrating and the headgroup charge can be tuned from +3 to -5 by altering the pH. The solution properties, studied by surface tension measurements and NMR diffusometry, were consequently found strongly pH dependent. pH measurements of chelating surfactant solutions as a function of concentration was used to extract information regarding the interaction between surfactants in the aggregation process. Small differences in the conditional stability constants (log K) between coordination complexes of DTPA and 4-C12-DTPA, determined by competition measurements utilizing electrospray ionization mass spectrometry (ESI-MS), indicated that the hydrocarbon tail only affected the chelating ability of the headgroup to a limited extent. This was further confirmed in hydrogen peroxide bleaching of thermomechanical pulp (TMP) treated with 4-C12-DTPA. Interaction parameters for mixed systems of 4-C12-DTPA and different foaming agents were calculated following the approach of Rubingh’s regular solution theory. The mixtures were also examined with addition of divalent metal ions in equimolar ratio to the chelating surfactant. Strong correlation was found between the interaction parameter and the phase transfer efficiency of Ni2+ ions during flotations. Furthermore, a significant difference in log K between different metal complexes with 4-C12-DTPA enabled selective recovery of the metal ion with the highest log K. The findings in this study contribute to the understanding of the fundamental characteristics of chelating surfactants, which can be further utilized in practical applications.

Block copolymers, long chain molecules of two distinct chemical species joined covalently to one another, have long been known to form organized structures on the nanoscopic level. For example, if the two chains are the same length a lamellar structure results . In this work we show how this internal structure causes distinct deviation from 'normal' fluid behavior. We begin with the observation of block copolymer droplets with atomic force microscopy. We note the droplets form nearly conical shapes in stark contrast to the usual spherical cap. These droplets are found t o spread at an incredibly slow speed, and to have interesting instabilities in their wetting layer. We move on to studies of completely wet substrates (i.e. thin films) near the order-disorder transition of the material. Here we directly observe, with optical microscopy, a change in the fundamental spacing of the diblock's internal structure. This represents a superior method of measurement of the Flory-Huggins interaction parameter, which we verify in several ways. We also use the change in lamellar thickness to drive diffusion from one layer to another, and by similar measurements we can determine the kinetics of diffusion between the lamellar layers. In the last study we measure the lamellar edges on a gradient thickness sample with optical microscopy. In so doing we can directly observe surface induced ordering, and for the first time, can precisely resolve the near surface ordering dynamics. / Thesis / Doctor of Philosophy (PhD)

The thermodynamic properties of CO2-mixtures are essential for the design and operation of CO2 Capture and Storage (CCS) systems. A better understanding of the thermodynamic properties of CO2 mixtures could provide a scientific basis to define a proper guideline of CO2 purity and impure components for the CCS processes according to technical, safety and environmental requirements. However the available accurate experimental data cannot cover the whole operation conditions of CCS processes. In order to overcome the shortage of experimental data, theoretical estimation and modelling are used as a supplemental approach.   In this thesis, the available experimental data on the thermodynamic properties of CO2 mixtures were first collected, and their applicability and gaps for theoretical model verification and calibration were also determined according to the required thermodynamic properties and operation conditions of CCS. Then in order to provide recommendations concerning calculation methods for engineering design of CCS, totally eight equations of state (EOS) were evaluated for the calculations about vapour liquid equilibrium (VLE) and density of CO2-mixtures, including N2, O2, SO2, Ar, H2S and CH4.   With the identified equations of state, the preliminary assessment of impurity impacts was further conducted regarding the thermodynamic properties of CO2-mixtures and different processes involved in CCS system. Results show that the increment of the mole fraction of non-condensable gases would make purification, compression and condensation more difficult. Comparatively N2 can be separated more easily from the CO2-mixtures than O2 and Ar. And a lower CO2 recovery rate is expected for the physical separation of CO2/N2 under the same separation conditions. In addition, the evaluations about the acceptable concentration of non-condensable impurities show that the transport conditions in vessels are more sensitive to the non-condensable impurities and it requires very low concentration of non-condensable impurities in order to avoid two-phase problems.   Meanwhile, the performances of evaporative gas turbine integrated with different CO2 capture technologies were investigated from both technical and economical aspects. It is concluded that the evaporative gas turbine (EvGT) cycle with chemical absorption capture has a smaller penalty on electrical efficiency, while a lower CO2 capture ratio than the EvGT cycle with O2/CO2 recycle combustion capture. Therefore, although EvGT + chemical absorption has a higher annual cost, it has a lower cost of electricity because of its higher efficiency. However considering its lower CO2 capture ratio, EvGT + chemical absorption has a higher cost to avoid 1 ton CO2. In addition the efficiency of EvGT + chemical absorption can be increased by optimizing Water/Air ratio, increasing the operating pressure of stripper and adding a flue gas condenser condensing out the excessive water. / QC 20100819