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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
91

CHARACTERIZATION OF COLLOIDAL NANOPARTICLE AGGREGATES USING LIGHT SCATTERING TECHNIQUES

Kozan, Mehmet 01 January 2007 (has links)
Light scattering is a powerful characterization tool for determining shape, size, and size distribution of fine particles, as well as complex, irregular structures of their aggregates. Small angle static light scattering and elliptically polarized light scattering techniques produce accurate results and provide real time, non-intrusive, and in-situ observations on prevailing process conditions in three-dimensional systems. As such, they complement conventional characterization tools such as SEM and TEM which have their known disadvantages and limitations. In this study, we provide a thorough light scattering analysis of colloidal tungsten trioxide (WO3) nanoparticles in the shape of irregular nanospheres and cylindrical nanowires, and of the resulting aggregate morphologies. Aggregation characteristics as a function of primary particle geometry, aspect ratio of nanowires, and the change in dispersion stability in various polar solvents without the use of dispersants are monitored over different time scales and are described using the concepts of fractal theory. Using forward scattered intensities, sedimentation rates as a result of electrolyte addition and particle concentration at low solution pH are quantified, in contrast to widely reported visual observations, and are related to the aggregate structure in the dispersed phase. For nanowires of high aspect ratios, when aggregate structures cannot directly be inferred from measurements, an analytical and a quasiexperimental method are used.
92

The Osmotic Second Virial Coefficient as a Predictor of Protein Stability

Verma, Kusum S 09 December 2006 (has links)
The number of protein containing therapeutic drugs is growing day by day. Lack of proper storage conditions can cause protein degradation or aggregation. The osmotic second virial coefficient, B22, is a thermodynamic parameter, which can predict protein interaction with other proteins and solvent molecules. B22 has been successfully used as predictor of crystallization conditions for a protein in the solution, and in this study an attempt has been made to relate B22 as a predictor of stability of the protein. Static light scattering was used to measure B22 in our studies. B22 and the solubility of three proteins were measured in several excipient solutions. George et al. in 1997 related the osmotic second virial coefficient with the solubility of protein in a solution. In this study we have attempted to relate solubility with B22 and stability of lysozyme, human serum albumin, and ovalbumin in buffer solutions containing various excipients.
93

Measuring and modelling light scattering in paper

Johansson, Niklas January 2015 (has links)
Avhandlingen behandlar de teoretiska och praktiska aspekterna av att använda spektrala vinkelupplösta reflektansmätningar för optisk karakterisering av fiberbaserade material såsom papper och kartong. En spektral goniofotometer används för att mäta det reflekterade ljusets vinkelfördelning. En stor del av arbetet utgörs av att utvärdera instrumentets noggrannhet, samt utreda hur de vinkelupplösta mätningarna skall utföras på bästa sätt för att erhålla en så fullständig karakterisering som möjligt. Det reflekterade ljuset består av tre komponenter; ytreflektans, bulkreflektans samt fluorescens. En fullständig karakterisering förutsätter att dessa tre komponenter kan analyseras separat, vilket i detta arbete görs genom nyutvecklade metoder. En metod har utvecklats för separation av ytreflektans och bulkreflektans. Metoden bygger på att analysera hur den totala reflektansen förändras vid ökande absorption i det reflekterande materialet. Absorptionen kontrolleras genom inkjet-tryckning där tryckfärg appliceras på substratet i sådan mängd att bulkreflektansen helt släcks ut. Genom att kombinera mätningar på tryckt och otryckt substrat kan de båda komponenterna separeras. Trots att ytreflektansen från ett matt papper är liten i förhållande till bulkreflektansen, så visar resultaten att den ökar markant med ökande betraktningsvinkel och kan därmed ha stor inverkan på den totala reflektansen. Bidraget från fluorescens kan kvantitativt analyseras genom att kombinera mätningar utförda med respektive utan UV-filter. Vinkelupplösta mätningar och Monte Carlo-simuleringar av fluorescensens vinkelfördelning visar att dess anisotropi är relaterad till det medeldjup vid vilket fluorescensen emitteras. Resultaten förklarar observerade skillnader och motstridigheter i tidigare rapporterade studier kring huruvida fluorescens kan anses vara Lamberskt fördelad. Samtliga goniofotometriska mätningar är utförda med ett kompakt, kommersiellt tillgängligt, dubbelstråleinstrument. För att undersöka instrumentets lämplighet för absoluta reflektansmätningar utförs en analys av dess mätnoggrannhet. Resultaten visar att instrumentets kompakta storlek i kombination med den anisotropa reflektansen från papper introducerar systematiska fel av samma storleksordning som den totala mätnoggrannheten. Dessa fel uppstår på grund av den relativt stora detektorapertur som måste användas vid mätningar av diffus reflektans, vilket är karakteristiskt för papper och kartong. Resultaten visar även att felen är störst vid flacka mätvinklar och för prover med hög grad av anisotropisk reflektans, och en geometrisk korrektionsmetod för denna typ av systematiska fel föreslås. Spektrala och vinkelupplösta mätningar medför per automatik stora mängder mätdata. Genom att använda strålningstransportteori som en matematisk modell för hur ljus sprids i papper kan mätdatat reduceras till en uppsättning beskrivande materialparameterar. Att uppskatta dessa optiska parametrar utifrån vinkelupplösta reflektansmätningar är i sig ett komplicerat problem, vilket dessutom är känsligt för mätfel och val av mätvinklar. Detta inversa problem analyseras i detalj, och speciellt hur valet av mätvinklar kan reduceras utan att försämra förutsättningarna för estimeringen. Simuleringar visar att mätningarna kan begränsas till infallsplanet, eller till och med enbart framåtriktningen, så länge tillräckligt flacka mätvinklar är inkluderade i mätsekvensen. / This thesis is about measuring and modelling light reflected from paper by using goniophotometric measurements. Measuring bidirectional reflectance requires highly accurate instruments, and a large part of the work in this thesis is about establishing the requirements that must be fulfilled to ensure valid data. A spectral goniophotometer is used for measuring the light reflected from paper and methods are developed for analyzing the different components, i.e. the fluorescence, surface reflectance and bulk reflectance, separately. A separation of the surface and bulk reflectance is obtained by inkjet printing and analyzing the total reflectance in the absorption band of the ink. The main principle of the method is to add dye to the paper until the bulk scattered light is completely absorbed. The remaining reflectance is solely surface reflectance, which is subtracted from the total reflectance of the undyed sample to give the bulk reflectance. The results show that although the surface reflectance of a matte paper is small in comparison with the bulk reflectance, it grows rapidly with increasing viewing angle, and can have a large influence on the overall reflectance. A method for quantitative fluorescence measurements is developed, and used for analyzing the angular distribution of the fluoresced light. The long-standing issue whether fluorescence from turbid (or amorphous) media is Lambertian or not, is resolved by using both angle-resolved luminescence measurements and radiative transfer based Monte Carlo simulations. It is concluded that the degree of anisotropy of the fluoresced light is related to the average depth of emission, which in turn depends on factors such as concentration of fluorophores, angle of incident light and the absorption coefficient at the excitation wavelength. All measurements are conducted with a commercially available benchtop sized double-beam spectral goniophotometer designed for laboratory use. To obtain reliable results, its absolute measurement capability is evaluated in terms of measurement accuracy. The results show that the compact size of the instrument, combined with the anisotropic nature of reflectance from paper, can introduce significant systematic errors of the same order as the overall measurement uncertainty. The errors are related to the relatively large detection solid angle that is required when measuring diffusely reflecting materials. Situations where the errors are most severe, oblique viewing angles and samples with high degree of anisotropic scattering, are identified, and a geometrical correction is developed. Estimating optical properties of a material from bidirectional measurements has proved to be a challenging problem and the outcome is highly dependent on both the quality and quantity of the measurements. This problem is analyzed in detail for optically thick turbid media, and the study targets the case when a restricted set of detection angles are available. This is the case when e.g. an unobstructed view of the sample is not possible. Simulations show that the measurements can be restricted to the plane of incidence (in-plane), and even the forward direction only, without any significant reduction in the precision or stability of the estimation, as long as sufficiently oblique angles are included.
94

Polymer hydrogel nanoparticles and their networks

Lu, Xihua 08 1900 (has links)
The thermally responsive hydroxypropyl cellulose (HPC) hydrogel nanoparticles have been synthesized and characterized. The HPC particles were obtained by chemically crosslinking collapsed HPC polymer chains in water-surfactant (dodecyltrimethylammonium bromide) dispersion above the lower critical solution temperature (LCST) of the HPC. The size distributions of microgel particles, measured by dynamic light scattering, have been correlated with synthesis conditions including surfactant concentration, polymer concentration, and reaction temperature. The swelling and phase transition properties of resultant HPC microgels have been analyzed using both static and dynamic light scattering techniques. By first making gel nanoparticles and then covalently bonding them together, we have engineered a new class of gels with two levels of structural hierarchy: the primary network is crosslinked polymer chains in each individual particle, while the secondary network is a system of crosslinked nanoparticles. The covalent bonding contributes to the structural stability of the nanostructured gels, while self-assembly provides them with crystal structures that diffract light, resulting in colors. By using N-isopropylacrylamide copolymer hydrogel nanoparticles, we have synthesized nanoparticle networks that display a striking iridescence like precious opal but are soft and flexible like gelatin. This is in contrast to previous colored hydrogels, which were created either by adding dyes or fluorescent, or by organic solvent or by embedding a colloidal crystal array of polymer solid spheres . Creating such periodic 3D structures in materials allows us to obtain useful functionality not only from the constituent building blocks but also from the long-range ordering that characterizes these structures. Hydroxypropyl cellulose (HPC) and poly (acrylic acid ) (PAA) complexes were studied using turbidity measurement and laser light scattering. The phase transition temperature of the complexes is found to depend on pH and molecular weights of PAA and HPC. The driving force for this phenomenon is due to the hydrogen bonding and hydrophobic interaction of the macromolecules. Based on the principle of the PAA/HPC complexes, the PAA nanoparticles were synthesized in 0.1wt % HPC aqueous solution at room temperature.
95

Synthesis and study of crystalline hydrogels, guided by a phase diagram.

Huang, Gang 12 1900 (has links)
Monodispersed nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) and PNIPAM-co-acrylic acid (AA) have been synthesized and used as building blocks for creating three-dimensional networks. The close-packed PNIPAM-co-allylamine and PNIPAM-co-AA nanoparticles were stabilized by covalently bonding neighboring particles at room temperature and at neutral pH; factors which make these networks amicable for drug loading and release. Controlled release studies have been performed on the networks using dextran markers of various molecular weights as model macromolecular drugs. Drug release was quantified under various physical conditions including a range of temperature and molecular weight. These nanoparticle networks have several advantages over the conventional bulk gels for controlling the release of biomolecules with large molecular weights. Monodispersed nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) can self-assemble into crystals with a lattice spacing on the order of the wavelength of visible light. By initiating the crystallization process near the colloidal crystal melting temperature, while subsequently bonding the PNIPAM-co-allylamine particles below the glass transition temperature, a nanostructured hydrogel has been created. The crystalline hydrogels exhibit iridescent patterns that are tunable by the change of temperature, pH value or even protein concentration. This kind of soft and wet hydrogel with periodic structures may lead to new sensors, devices, and displays operating in aqueous solutions, where most biological and biomedical systems reside. The volume-transition equilibrium and the interaction potential between neutral PINPAM particles dispersed in pure water were investigated by using static and dynamic light-scattering experiments. From the temperature-dependent size and energy parameters, the Sutherland-like potential provides a reasonable representation of the inter-particle potential for PNIPAM particles in swollen and in collapsed phases. An aqueous dispersion of PNIPAM particles can freeze at both high and low temperatures. At low temperatures, the freezing occurs at a large particle volume fraction, similar to that in a hard-sphere system; while at high temperature, the freezing occurs at low particle concentrations, driven by the strong van der Waals attraction due to the collapsed microgel particles. The calculated phase diagram has been confirmed semi-quantitatively by experiments.
96

Calibration and Performance Evaluation for a Multiple Overlapping Field of View Serial Laser Imager

Unknown Date (has links)
The Combined Laser and Scan Sonar (CLASS) system is an extended range imaging system, incorporating both high-resolution laser images and high frequency sonar images. Both the laser and sonar images are collected simultaneously during testing to provide dual mode imagery of an underwater target, displaying both a 2D image of the target (laser image) and a 3D overlay of the target (sonar image). The laser component of the system is a Multiple Overlapping Field of view Serial Laser Imager (MOFSLI), capable of generating high-resolution sub-centimeter 2D images. MOFSLI generates the images by way of a near diffraction-limited 532 [nm] continuous wave (CW) laser beam being scanned over the target. Initial field tests resulted in high-quality images of the ocean floor, but also indicated the need for additional research on MOFSLI. In this thesis, we focus on the calibration of MOFSLI and on the evaluation of the image quality generated by this system, as a function of range, source power, receiver gain and water turbidity. This work was completed in the specialized underwater electrooptics testing facility located in the Ocean Visibility and Optics laboratory at Harbor Branch Oceanographic Institute (HBOI). Laboratory testing revealed the operational limits of the system, which functioned well until just beyond five attenuation lengths, where it becomes contrast limited due attenuation of target signal and the collection of non-image bearing backscattered photons. Testing also revealed the optimal settings of the system at given environmental conditions. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection
97

Phase conjugation by stimulated Brillouin scattering and by stimulated Raman scattering.

January 1984 (has links)
by Yip Sung-tat. / Bibliography: leaves 120-123 / Thesis (M.Ph.)--Chinese University of Hong Kong, 1984
98

Investigation of Physical Characteristics Impacting Fate and Transport of Viral Surrogates in Water Systems

Charest, Abigail J. 29 January 2015 (has links)
A multi-scale approach was used to investigate the occurrence and physical characteristics of viral surrogates in water systems. This approach resulted in a methodology to quantify the dynamics and physical parameters of viral surrogates, including bacteriophages and nanoparticles. Physical parameters impacting the occurrence and survival of viruses can be incorporated into models that predict the levels of viral contamination in specific types of water. Multiple full-scale water systems (U.S., Italy and Australia) were tested including surface water, drinking water, stormwater and wastewater systems. Water quality parameters assessed included viral markers (TTV, polyomavirus, microviridae and adenovirus), bacteriophages (MS2 and ΦX-174), and coliforms (total coliforms and E. coli). In this study, the lack of correlations between adenovirus and that of bacterial indicators suggests that these bacterial indicators are not suitable as indicators of viral contamination. In the wastewater samples, microviridae were correlated to the adenovirus, polyomavirus, and TTV. While TTV may have some qualities which are consistent with an indicator such as physical similarity to enteric viruses and occurrence in populations worldwide, the use of TTV as an indicator may be limited as a result of the detection occurrence. The limitations of TTV may impede further analysis and other makers such as coliphages, and microviridae may be easier to study in the near future. Batch scale adsorption tests were conducted. Protein-coated latex nanospheres were used to model bacteriophages (MS2 and ΦX-174) and includes a comparison of the zeta potentials in lab water, and two artificial groundwaters with monovalent and divalent electrolytes. This research shows that protein-coated particles have higher average log10 removals than uncoated particles. Although, the method of fluorescently labeling nanoparticles may not provide consistent data at the nanoscale. The results show both that research on viruses at any scale can be difficult and that new methodologies are needed to analyze virus characteristics in water systems. A new dynamic light scattering methodology, area recorded generalized optical scattering (ARGOS) method, was developed for observing the dynamics of nanoparticles, including bacteriophages MS2 and ΦX-174. This method should be further utilized to predict virus fate and transport in environmental systems and through treatment processes. While the concentration of MS2 is higher than ΦX-174 as demonstrated by relative total intensity, the RMSD shows that the dynamics are greater and have more variation in ΦX-174 than MS2 and this may be a result of the hydrophobic nature of ΦX-174. Relationships such as these should be further explored, and may reflect relationships such as particle bonds or hydrophobicity.
99

Studies of nonlinear light scattering in organic liquids and metal colloids. / 由有機液體以及金屬膠體產生的非線性光散射的研究 / CUHK electronic theses & dissertations collection / Studies of nonlinear light scattering in organic liquids and metal colloids. / You you ji ye ti yi ji jin shu jiao ti chan sheng de fei xian xing guang san she de yan jiu

January 2009 (has links)
In our research Hyper-Rayleigh scattering (HRS) is employed as an effective, simple investigation technique to study solutions of small molecules, pure liquids, nano-adsorbing systems and metal colloids. A set of apparatus has been built with good spectral resolution and high sensitivity to successfully measure characteristics of intensity and polarization properties of HRS. It was found that the consistency was different for pure liquid and solutions of small molecules when comparing experimental measurements of depolarized ratios and polarization patterns with theoretical expectations. This is due to the presence of both incoherent and coherent contributions to HRS in pure liquids, of which the origin of the coherent contribution is different for different pure liquids. In our results, pure liquid nitrobenzene was found to have strong coherent contribution to HRS caused by intermolecular interactions. Three different chemical compounds were used to mix with nitrobenzene to break the strong orientational correlations between molecules. Comparison between the results show different behaviors in the effectiveness in eliminating the coherent HRS signals, and the effectiveness was correlated to the molecular structures. Theory of second harmonic scattering from surface has been expanded as leading order contributions containing nonlocal electric dipole mode and local quadrupole mode, which can be exhibited in our experimental study of polarization patterns. Polarization patterns from polystyrene particles of different sizes adsorbed with different species of dyes were measured to investigate and compare with theoretical expectations. For small-size adsorbing system, measurements of polarization patterns were basically consistent with theory. However, for adsorbing system of polystyrene particles with a size of 900 nm, the polarization patterns showed discrepancies when comparing with theory, which indicated that higher order multipoles are needed in the theory. Silver and gold colloids were employed as the subject of investigation for measuring the polarization patterns of HRS. The results were found to be consistent when comparing with their extinction spectra and TEM images. We have managed to measure polarization patterns of HRS originated from surface of non-spherical colloids and the results showed that the origin of HRS can be qualitatively understood, although a more elaborated theory is needed to describe the data. / by Chen, Ji = 由有機液體以及金屬膠體產生的非線性光散射的研究 / 陳佶. / Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 117-118). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307. / by Chen, Ji = You you ji ye ti yi ji jin shu jiao ti chan sheng de fei xian xing guang san she de yan jiu / Chen Ji.
100

Crystallographic and spectroscopic assessment of pharmaceutical material mechanics

Singaraju, Aditya Bharadwaj 01 December 2018 (has links)
Despite the advent of alternative dosage forms, solid dosage forms constitute a major proportion of dosage forms not only on the market, but also in many pharmaceutical companies’ pipelines. This is because of their superior stability and ease of manufacturing relative to other dosage forms. Although solid dosage forms have been the topic of discussion for decades, the process of compaction of these dosage forms is considered an art rather than science because of the empiricism that exists in this area. With the introduction of Quality by Design (QbD), it is imperative that the drug development process is guided by structured scientific principles. It has been hypothesized that crystal structure of organic solids plays a pivotal role in understanding the properties, processing and eventually performance of solids. In this regard, the intermolecular interactions within a solid play a paramount role in dictating the materials response to stress. One important parameter that is weakly addressed in the literature is the concept of strength of intermolecular interactions. In the current work, we utilize the concept of elasticity as a metric for strength of intermolecular interactions. We introduce powder Brillouin light scattering; an inelastic light scattering technique to measure the elasticity of organic solids and try to correlate the mechanical moduli extracted from the spectra to the compaction performance of solids. We hypothesize that any redistribution of intermolecular interactions would be reflected in the BLS spectrum of these materials and the material properties can be used to explain the differences in compaction performance. Before we tested our hypothesis, we validated our powder BLS technique using aspirin as model system. We then applied the same analysis to four model systems that involved different ways of reorganizing the intermolecular interactions upon subtle modifications to the molecular structure. In Chapter 4, we investigated the effect of alkyl chain length and crystal structure on the mechanical properties and compaction performance of p-aminobenzoic acid (PABA) and its esters. For the entire ester series, a similar hydrogen bonding pattern was observed with strong N-H…O (carbonyl) and supportive N-H…N interactions. While the ethyl and butyl esters exhibited a layered structure, the methyl ester displayed a 3-D isotropic structure. The crystal structure for PABA exhibited a three-dimensional, quasi-isotropic distribution of the hydrogen-bonding interactions that connected the PABA dimers. The powder BLS spectra for these materials revealed low velocity shear modes for the layered structures and a spectrum consistent with an isotropic structure for Me-PABA and PABA. This was in good agreement with the compressibility behavior under load, with Et-PABA and Bu-PABA more compressible than PABA. However, due to greater particle-particle adhesion, PABA compacts showed greater tensile strength at higher pressures. The moduli calculated also showed that both Et-PABA and Bu-PABA had lower shear and Young’s modulus relative to the other materials. Attachment energies corroborated the above results. These studies showed that weak dispersive forces play an important role in understanding material properties. In Chapter 5, a series of nitrobenzoic derivatives were used to study the effect of secondary interactions on the crystal reorganization and material properties. The materials used in the study include p-nitrobenzoic acid (4-NBA), m-nitrobenzoic acid (3-NBA, 4-chloro-3-nitrobenzoic acid (Cl-NBA), 4-bromo-3-nitrobenzoic acid (Br-NBA), and 4-methyl-3-nitrobenzoic acid (Me-NBA). Crystal structures of the materials revealed different organization of C-H…O interactions. Two types of C-H…O interactions were prevalent namely C-H…O (nitro) and C-H…O (carboxy). The reorganization of these two types of interactions led to different packing motifs and different mechanical behavior. These structural features were reflected in their mechanical properties assessed by powder Brillouin light scattering. Cl-NBA and Br-NBA displayed an isotropic spectrum similar to polystyrene and aspirin. 3-NBA, 4-NBA and Me-NBA displayed different spectra from Cl-NBA and Br-NBA with high frequency tailing in the longitudinal mode distribution indicating a specific direction of extended molecular interactions. The Young’s modulus and shear modulus followed the order: 3-NBA < Me-NBA< 4-NBA < Cl-NBA < Br-NBA. The maximum longitudinal modulus Mmax was the highest for 3-NBA and was significantly greater than rest of the materials. From the compaction studies, it was observed that the tabletability followed the rank order 3-NBA > 4-NBA > Me-NBA ≈ Br-NBA ≈ Cl-NBA which is the same order as Mmax. 3-NBA by virtue of its low shear and Young’s modulus to be the most compressible material, but the compressibility rank order was 4-NBA > Me-NBA ≈ 3-NBA > Cl-NBA > Br-NBA. However, 3-NBA by virtue of its greater particle-particle adhesion was the most compactable material. The yield pressures obtained from Heckel plots revealed that 4-NBA and Me-NBA were relatively more plastic when compared to the other materials. This study demonstrated that subtle changes to the molecular structure can result in drastically different crystal packing which in turn would influence the mechanical properties and the compaction performance of organic solids. In Chapter 6, we investigated the effect of cocrystallization on the compaction performance of caffeine(CAF). The series of halo-nitrobenzoic acids (F-NBA, Cl-NBA and 3-NBA) were used as coformers. The cocrystals CAF: F-NBA, CAF: Cl-NBA and CAF: NBA Form 1 adopted a flat layered structure that can undergo deformation with ease. This increased the compressibility of the cocrystals relative to CAF. In addition to the improved compressibility, by virtue of increased particle-particle contacts, the cocrystals also displayed superior tabletability. In contrast to the layered structures adopted by the three cocrystals, the CAF: NBA Form 2 displayed a columnar structure that exhibited resistance to stress. The compressibility and the tabletability of CAF: NBA Form 2 was significantly compromised when compared to that of Form1. All the compaction characteristics of the cocrystals were in good agreement with moduli and parameters obtained from powder BLS spectra. The layered materials showed the presence of low velocity shear modes corroborating the earlier studies. There was a clear difference in the spectra of the polymorphs, indicating that powder BLS can be used for mechanical screening of polymorphs. In Chapter 7, we examined the effects of crystal structure and coformer functionality on the compaction performance of theophylline (THY). The coformers employed include 4-fluoro-3-nitrobenzoic acid (FNBA), acetaminophen (APAP), and p-aminobenzoic acid (PABA). While THY-APAP and THY-FNBA exhibited layered structures, the THY-PABA displayed a interdigitated columnar structure. Powder BLS spectra showed the presence of low frequency shear modes relative to THY for all the three cocrystals. However, the order of frequencies followed: THY-FNBA < THY-APAP < THY-PABA. The shear modulus calculated followed the order THY-APAP≈ THY-FNBA < THY < THY-PABA which is in agreement with the crystal structures discussed. The Young’s modulus followed the order THY-FNBA < THY-APAP < THY < THY-PABA. The two layered structures (THY-APAP, THY-FNBA) showed distinct compaction performance (similar compressibility but different compactability and tabletability). The layered structures were more compressible than THY which is hypothesized to undergo deformation through multiple mechanisms. THY-PABA showed poor compaction properties. This highlights the fact that although the coformer (PABA) is molecularly similar to FNBA, the resultant cocrystals are structurally and mechanically distinct. These observations were well supported by the moduli calculated from powder BLS studies. The order of yield pressures obtained from Heckel analysis followed the same order as shear modulus. The tensile strength of the compacts of the cocrystals level off at around 150 MPa but the tensile strength of THY compacts continues to increase. From a manufacturing perspective the cocrystals can prove to be a better option as they as more compactable at higher porosities or they possess greater tabletability at low compaction pressures. Overall, we have used model systems to demonstrate that the redistribution of intermolecular forces upon point substitution or cocrystallization have a dramatic effect on the material properties. It is also worth noting that elasticity along with plasticity can provide important information about the strength of interactions which would help in understanding the role of weak intermolecular forces in the performance of organic materials. To gain a better perspective of the compaction process and move towards a QbD approach, it is also imperative to understand the link between crystal structures, intermolecular interactions which is possible with the help of novel characterization techniques (BLS, AFM).

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