Mechanical properties and structure of gel systems

Understanding the origins of the mechanical properties and its correlation withrnthe microstructure of gel systems is of great scientific and industrial interest. Inrngeneral, colloidal gels can be classified into chemical and physical gels, accordingrnto the life time of the network bonds. The characteristic di↵erences in gelationrndynamics can be observed with rheological measurements.rnAs a model system, a mixture of sodium silicate and low concentration sulfuric acidrnwas used. Nano-sized silica particles grow and aggregate to a system-spanning gelrnnetwork. The influence of the finite solubility of silica at high pH on the gelationrnwas studied with classical and piezo rheometer. The storage modulus of therngel grew logarithmically with time with two distinct growth laws. A relaxationrnat low frequency was observed in the frequency dependent measurements. I attributernthese two behaviors as a sign of structural rearrangements due to the finiternsolubility of silica at high pH. The reaction equilibrium between formation andrndissolution of bonds leads to a finite life time of the bonds and behavior similar tornphysical gel. The frequency dependence was more pronounced for lower water concentrations,rnhigher temperatures and shorter reaction times. With two relaxationrnmodels, I deduced characteristic relaxation times from the experimental data. Besidesrnrheology, the evolution of silica gels at high pH on di↵erent length scales wasrnstudied by NMR and dynamic light scattering. The results revealed that the primaryrnparticles existed already in sodium silicate and aggregated after the mixingrnof reactants due to a chemical reaction. Throughout the aggregation process thernsystem was in its chemical reaction equilibrium. Applying large oscillatory shearrnstrain to the gel allowed for modifying the gel modulus. The e↵ect of shear andrnshear history on the rheological properties of the gel were investigated. The storagernmodulus of the final gel increased with increasing strain. This behavior can be explained with (i) shear-induced aggregate compaction and (ii) combination ofrnbreakage and new formation of bonds.rnIn comparison with the physical gel-like behavior of the silica gel at high pH, typicalrnchemical gel features were exhibited by other gels formed from various chemicalrnreactions. Influences of the chemical structure modification on the gelation wererninvestigated with the piezo-rheometer. The external stimuli can be applied to tunernthe mechanical properties of the gel systems.

From lipid bilayers to synaptic vesicles: atomic force microscopy on lipid-based systems

The aim of this thesis was to apply the techniques of the atomic force microscope (AFM) to biological samples, namely lipid-based systems. To this end several systems with biological relevance based on self-assembly, such as a solid-supported membrane (SSM) based sensor for transport proteins, a bilayer of the natural lipid extract from an archaebacterium, and synaptic vesicles, were investigated by the AFM. For the characterization of transport proteins with SSM-sensors proteoliposomes are adsorbed that contain the analyte (transport protein). However the forces governing bilayer-bilayer interactions in solution should be repulsive under physiological conditions. I investigated the nature of the interaction forces with AFM force spectroscopy by mimicking the adsorbing proteoliposome with a cantilever tip, which was functionalized with charged alkane thiols. The nature of the interaction is indeed repulsive, but the lipid layers assemble in stacks on the SSM, which expose their unfavourable edges to the medium. I propose a model by which the proteoliposomes interact with these edges and fuse with the bilayer stacks, so forming a uniform layer on the SSM. Furthermore I characterized freestanding bilayers from a synthetic phospholipid with a phase transition at 41°C and from a natural lipid extract of the archaebacterium Methanococcus jannaschii. The synthetic lipid is in the gel-phase at room temperature and changes to the fluid phase when heated to 50°C. The bilayer of the lipid extract shows no phase transition when heated from room temperature to the growth temperature (~ 50°C) of the archeon. Synaptic vesicles are the containers of neurotransmitter in nerve cells and the synapsins are a family of extrinsic membrane proteins, that are associated with them, and believed to control the synaptic vesicle cycle. I used AFM imaging and force spectroscopy together with dynamic light scattering to investigate the influence of synapsin I on synaptic vesicles. To this end I used native, untreated synaptic vesicles and compared them to synapsin-depleted synaptic vesicles. Synapsin-depleted vesicles were larger in size and showed a higher tendency to aggregate compared to native vesicles, although their mechanical properties were alike. I also measured the aggregation kinetics of synaptic vesicles induced by synapsin I and found that the addition of synapsin I promotes a rapid aggregation of synaptic vesicles. The data indicate that synapsin I affects the stability and the aggregation state of synaptic vesicles, and confirm the physiological role of synapsins in the assembly and regulation of synaptic vesicle pools within nerve cells.

Structure property relations in complex copolymer systems

A thorough investigation was made of the structure-property relation of well-defined statistical, gradient and block copolymers of various compositions. Among the copolymers studied were those which were synthesized using isobornyl acrylate (IBA) and n-butyl acrylate (nBA) monomer units. The copolymers exhibited several unique properties that make them suitable materials for a range of applications. The thermomechanical properties of these new materials were compared to acrylate homopolymers. By the proper choice of the IBA/nBA monomer ratio, it was possible to tune the glass transition temperature of the statistical P(IBA-co-nBA) copolymers. The measured Tg’s of the copolymers with different IBA/nBA monomer ratios followed a trend that fitted well with the Fox equation prediction. While statistical copolymers showed a single glass transition (Tg between -50 and 90 ºC depending on composition), DSC block copolymers showed two Tg’s and the gradient copolymer showed a single, but very broad, glass transition. PMBL-PBA-PMBL triblock copolymers of different composition ratios were also studied and revealed a microphase separated morphology of mostly cylindrical PMBL domains hexagonally arranged in the PBA matrix. DMA studies confirmed the phase separated morphology of the copolymers. Tensile studies showed the linear PMBL-PBA-PMBL triblock copolymers having a relatively low elongation at break that was increased by replacing the PMBL hard blocks with the less brittle random PMBL-r-PMMA blocks. The 10- and 20-arm PBA-PMBL copolymers which were studied revealed even more unique properties. SAXS results showed a mixture of cylindrical PMBL domains hexagonally arranged in the PBA matrix, as well as lamellar. Despite PMBL’s brittleness, the triblock and multi-arm PBA-PMBL copolymers could become suitable materials for high temperature applications due to PMBL’s high glass transition temperature and high thermal stability. The structure-property relation of multi-arm star PBA-PMMA block copolymers was also investigated. Small-angle X-ray scattering revealed a phase separated morphology of cylindrical PMMA domains hexagonally arranged in the PBA matrix. DMA studies found that these materials possess typical elastomeric behavior in a broad range of service temperatures up to at least 250°C. The ultimate tensile strength and the elastic modulus of the 10- and 20-arm star PBA-PMMA block copolymers are significantly higher than those of their 3-arm or linear ABA type counterparts with similar composition, indicating a strong effect of the number of arms on the tensile properties. Siloxane-based copolymers were also studied and one of the main objectives here was to examine the possibility to synthesize trifluoropropyl-containing siloxane copolymers of gradient distribution of trifluoropropyl groups along the chain. DMA results of the PDMS-PMTFPS siloxane copolymers synthesized via simultaneous copolymerization showed that due to the large difference in reactivity rates of 2,4,6-tris(3,3,3-trifluoropropyl)-2,4,6-trimethylcyclotrisiloxane (F) and hexamethylcyclotrisiloxane (D), a copolymer of almost block structure containing only a narrow intermediate fragment with gradient distribution of the component units was obtained. A more dispersed distribution of the trifluoropropyl groups was obtained by the semi-batch copolymerization process, as the DMA results revealed more ‘‘pure gradient type’’ features for the siloxane copolymers which were synthesized by adding F at a controlled rate to the polymerization of the less reactive D. As with trifluoropropyl-containing siloxane copolymers, vinyl-containing polysiloxanes may be converted to a variety of useful polysiloxane materials by chemical modification. But much like the trifluoropropyl-containing siloxane copolymers, as a result of so much difference in the reactivities between the component units 2,4,6-trivinyl-2,4,6-trimethylcyclotrisiloxane (V) and hexamethylcyclotrisiloxane (D), thermal and mechanical properties of the PDMS-PMVS copolymers obtained by simultaneous copolymerization was similar to those of block copolymers. Only the copolymers obtained by semi-batch method showed properties typical for gradient copolymers.

Wet and dry model granulates under mechanical load : a confocal microscopy study

Granular matter, also known as bulk solids, consists of discrete particles with sizes between micrometers and meters. They are present in many industrial applications as well as daily life, like in food processing, pharmaceutics or in the oil and mining industry. When handling granular matter the bulk solids are stored, mixed, conveyed or filtered. These techniques are based on observations in macroscopic experiments, i.e. rheological examinations of the bulk properties. Despite the amply investigations of bulk mechanics, the relation between single particle motion and macroscopic behavior is still not well understood. For exploring the microscopic properties on a single particle level, 3D imaging techniques are required.rnThe objective of this work was the investigation of single particle motions in a bulk system in 3D under an external mechanical load, i.e. compression and shear. During the mechanical load the structural and dynamical properties of these systems were examined with confocal microscopy. Therefor new granular model systems in the wet and dry state were designed and prepared. As the particles are solid bodies, their motion is described by six degrees of freedom. To explore their entire motion with all degrees of freedom, a technique to visualize the rotation of spherical micrometer sized particles in 3D was developed. rnOne of the foci during this dissertation was a model system for dry cohesive granular matter. In such systems the particle motion during a compression of the granular matter was investigated. In general the rotation of single particles was the more sensitive parameter compared to the translation. In regions with large structural changes the rotation had an earlier onset than the translation. In granular systems under shear, shear dilatation and shear zone formation were observed. Globally the granular sediments showed a shear behavior, which was known already from classical shear experiments, for example with Jenike cells. Locally the shear zone formation was enhanced, when near the applied load a pre-diluted region existed. In regions with constant volume fraction a mixing between the different particle layers occurred. In particular an exchange of particles between the current flowing region and the non-flowing region was observed. rnThe second focus was on model systems for wet granular matter, where an additional binding liquid is added to the particle suspension. To examine the 3D structure of the binding liquid on the micrometer scale independently from the particles, a second illumination and detection beam path was implemented. In shear and compression experiments of wet clusters and bulk systems completely different dynamics compared to dry cohesive models systems occured. In a Pickering emulsion-like system large structural changes predominantly occurred in the local environment of binding liquid droplets. These large local structural changes were due to an energy interplay between the energy stored in the binding droplet during its deformation and the binding energy of particles at the droplet interface. rnConfocal microscopy in combination with nanoindentation gave new insights into the single particle motions and dynamics of granular systems under a mechanical load. These novel experimental results can help to improve the understanding of the relationship between bulk properties of granular matter, such as volume fraction or yield stress and the dynamics on a single particle level.rnrn

Hydrodynamics and solid dosage form disintegration/dissolution : immediate release tablets and novel in situ polyelectrolyte gastroretentive drug delivery systems

Solid oral dosage form disintegration in the human stomach is a highly complex process dependent on physicochemical properties of the stomach contents as well as on physical variables such as hydrodynamics and mechanical stress. Understanding the role of hydrodynamics and forces in disintegration of oral solid dosage forms can help to improve in vitro disintegration testing and the predictive power of the in vitro test. The aim of this work was to obtain a deep understanding of the influence of changing hydrodynamic conditions on solid oral dosage form performance. Therefore, the hydrodynamic conditions and forces present in the compendial PhEur/USP disintegration test device were characterized using a computational fluid dynamics (CFD) approach. Furthermore, a modified device was developed and the hydrodynamic conditions present were simulated using CFD. This modified device was applied in two case studies comprising immediate release (IR) tablets and gastroretentive drug delivery systems (GRDDS). Due to the description of movement provided in the PhEur, the movement velocity of the basket-rack assembly follows a sinusoidal profile. Therefore, hydrodynamic conditions are changing continually throughout the movement cycle. CFD simulations revealed that the dosage form is exposed to a wide range of fluid velocities and shear forces during the test. The hydrodynamic conditions in the compendial device are highly variable and cannot be controlled. A new, modified disintegration test device based on computerized numerical control (CNC) technique was developed. The modified device can be moved in all three dimensions and radial movement is also possible. Simple and complex moving profiles can be developed and the influence of the hydrodynamic conditions on oral solid dosage form performance can be evaluated. Furthermore, a modified basket was designed that allows two-sided fluid flow. CFD simulations of the hydrodynamics and forces in the modified device revealed significant differences in the fluid flow field and forces when compared to the compendial device. Due to the CNC technique moving velocity and direction are arbitrary and hydrodynamics become controllable. The modified disintegration test device was utilized to examine the influence of moving velocity on disintegration times of IR tablets. Insights into the influence of moving speed, medium viscosity and basket design on disintegration times were obtained. An exponential relationship between moving velocity of the modified basket and disintegration times was established in simulated gastric fluid. The same relationship was found between the disintegration times and the CFD predicted average shear stress on the tablet surface. Furthermore, a GRDDS was developed based on the approach of an in situ polyelectrolyte complex (PEC). Different complexes composed of different grades of chitosan and carrageenan and different ratios of those were investigated for their swelling behavior, mechanical stability, and in vitro drug release. With an optimized formulation the influence of changing hydrodynamic conditions on the swelling behavior and the drug release profile was demonstrated using the modified disintegration test device. Both, swelling behavior and drug release, were largely dependent on the hydrodynamic conditions. Concluding, it has been shown within this thesis that the application of the modified disintegration test device allows for detailed insights into the influence of hydrodynamic conditions on solid oral dosage form disintegration and dissolution. By the application of appropriate test conditions, the predictive power of in vitro disintegration testing can be improved using the modified disintegration test device. Furthermore, CFD has proven a powerful tool to examine the hydrodynamics and forces in the compendial as well as in the modified disintegration test device. rn

Synthesis and application of stimuli responsive tunable systems based on physical interactions

Novel single step synthetic procedure for hydrophobically modified alkali soluble latexes (HASE) via a miniemulsion-analogous method is presented. This facile method simplifies the copolymerization of the monomers with basically “opposite” character in terms of their hydrophilic/hydrophobic nature, which represent one of the main challenges in water based systems. Considered systems do not represent classical miniemulsions due to a high content of water soluble monomers. However, the polymerization mechanism was found to be rather similar to miniemulsion polymerization process.rnThe influence of the different factors on the system stability has been investigated. The copolymerization behavior studies typically showed strong composition drifts during copolymerization. It was found that the copolymer composition drift can be suppressed via changing the initial monomer ratio.rnThe neutralization behavior of the obtained HASE systems was investigated via potentiometric titration. The rheological behavior of the obtained systems as a function of the different parameters, such as pH, composition (ultrahydrophobe content) and additive type and content has also been investigated.rnDetailed investigation of the storage and loss moduli, damping factor and the crossover frequencies of the samples showed that at the initial stages of the neutralization the systems show microgel-like behavior.rnThe dependence of the rheological properties on the content and the type of the ultrahydrophobe showed that the tuning of the mechanical properties can be easily achieved via minor (few percent) but significant changes in the content of the latter. Besides, changing the hydrophobicity of the ultrahydrophobe via increasing the carbon chain length represents another simple method for achieving the same results.rnThe influence of amphiphilic additives (especially alcohols) on the rheological behavior of the obtained systems has been studied. An analogy was made between micellation of surfactants and the formation of hydrophobic domains between hydrophobic groups of the polymer side chain.rnDilution induced viscosity reduction was investigated in different systems, without or with different amounts or types of the amphiphilic additive. Possibility of the controlled response to dilution was explored. It was concluded that the sensitivity towards dilution can be reduced, and in extreme cases even the increase of the dynamic modulus can be observed, which is of high importance for the setting behavior of the adhesive material.rnIn the last part of this work, the adhesive behavior of the obtained HASE systems was investigated on different substrates (polypropylene and glass) for the standard labeling paper. Wet tack and setting behavior was studied and the trends for possible applications have been evaluated.rnThe novel synthetic procedure, investigation of rheological properties and the possibility of the tuning via additives, investigated in this work create a firm background for the development of the HASE based adhesives as well as rheology modifiers with vast variety of possible applications due to ease of tuning the mechanical and rheological properties of the systems.