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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).

As features on integrated circuits continue to shrink, currently at 22 nm and predicted to approach 10 nm by 2020, the semiconductor industry is rapidly brushing up against the fundamental limits of electric charge and current based devices. These limits are due to the fact that charges are being pushed around in tiny areas and they repel one another with significant force. Fortunately, there are many other degrees of freedom in solids that do not suffer from these limitations and are just waiting to be harnessed in useful devices. This idea is behind all of the fields that have lately been proliferating ending in -onics, photonics, plasmonics, phononics, and of most relevance to this dissertation spintronics. Spintronics refers to a field of research wherein ways are sought to utilize the spin property of the electron in devices. One of the most attractive aspects of electron spin is that it can be used to store (transiently or permanently), process, and transmit information. The main challenge in spintronics is accessing the spin degree of freedom. Until the discovery of the giant magnetoresistance effect in the late 1980's, the only way to manipulate the electron spin was through a magnetic field. Recent developments have shown that electron spins can be controlled with direct currents of both heat and electrons, which have the benefit of being easy to generate and direct without interfering over a large area. The purpose of this dissertation is to study methods of controlling the dynamics of magnetization in thin films for spintronic applications by imaging the spin wave intensity in devices. To this end we have constructed a micro-focus Brillouin Light Scattering system to map the intensity of spin waves propagating in thin ferromagnetic films on the sub-micron scale. We have studied issues relating to fundamental issues of spin wave propagation in thin films. We have investigated the possibility of spin wave amplification with direct charge currents and spin currents generated by the spin Hall effect. Furthermore, we have demonstrated the ability to measure the magnon and phonon temperatures, which is important for studies of thermal transport. / text

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Spinové vlny mají potenciál být použity jako nová platforma pro přenos a zpracování dat, protože mohou dosáhnout vlnových délek v rozsahu nanometrů a frekvencí v rozsahu terahertzů. K tomu, aby bylo možné navrhnout zařízení a logické obvody založené na spinových vlnách, je zapotřebí získat informace o prostorovém rozložení intenzity spinové vlny a pokud je to možné, také o jejich fázi. To lze měřit pomocí fázově rozlišeného fokuso-vaného Brillouinova rozptylu světla (µ -BLS). Předložená práce se zabývá rozšířením stávající optické sestavy o možnost měření fáze, kde doposud bylo možné měřit pouze intenzitu. Toto rozšíření sestavy je důkladně popsáno a charakterizováno. Schopnosti optické sestavy jsou demonstrovány ve studii šíření spinových vln skrz Néelovu doménovou stěnu. Získané 2D mapy intenzity spinových vln ukazují, že propagace přes doménovou stěnu je ovlivněna topologicky vynucenou kruhovou Blochovou čarou ve středu doménové stěny a že režim propagace závisí na frekvenci spinových vln. V prvním režimu propagace se vytvoří dva svazky spinových vlny šířící se kolem kruhové Blochovy čáry, zatímco ve druhém režimu se spinové vlny šíří pouze středem. Fázově rozlišené µ-BLS měření odhaluje fázový po- sun spinových vln pro oba režimy. Mikromagnetické modelování spinových vln ukazuje rozrušení jejich fázových vlnoploch, které je třeba brát v úvahu při interpretaci měření a navrhování potenciálních zařízení. Mikromagnetické simulace ukazují, že vnější magnetické pole může být použito k pohybu kruhové Blochovy čáry ve stěně domény, a tedy k manipulaci spinových vln.

Zařízení založená na spinových vlnách mají potenciál být využita ve výpočetní technice s nízkou spotřebou energie. Pro úspěšné využití je samozřejmě potřeba spojit více takových zařízení na jednom čipu, součástí čehož musí být zatáčení spinových vln zahnutými vlnovody. Problém zatáčení spinových vln v dipolárně výměnném režimu zatím nebyl uspokojivě vyřešen, vyzkoušené přístupy vedly ke ztrátě intenzity a fázové koherence. V této diplomové práci jsme zkoumali dva systémy, které by mohly být využity k zatáčení spinových vln. Prvním z nich jsou tenké metastabilní vrstvy slitiny železa a niklu. Paramagnetická metastabilní fcc vrstva, která byla epitaxně narostena na substrátu z mědi, může být transformována do stabilní ferromagnetické bcc fáze pomocí fokusovaného iontového svazku. Tato technika nám dává prostorovou kontrolu nad transformačním procesem a strategie skenování svazkem nám dokonce umožňuje určit směr mangetické anisotropie. Magnetické vlastnosti struktur vytvořených touto metodou a lom spinových vln mezi doménami s odlišným směrem magnetické anisotropie byly změřeny pomocí mikroskopie Brillouinova rozptylu světla. Druhým zkoumaným systémem jsou zvlněné vlnovody, jejichž zvlnění indukuje magnetickou anisotropii. Zvlnění magnetické vrstvy je vytvořeno depozicí nemagnetických vlnek na substrátu indukovanou fokusovaným elektronovým svazkem a následnou depozicí magnetického materiálu. Byly vyrobeny různé návrhy zatočených zvlněných vlnovodů a změřili jsme šíření spinových vln jejich zatáčkami pomocí mikroskopie Brillouinova rozptylu světla. Využili jsme také mikromagnetické simulace pro získání hlubšího porozumění zkoumané problematiky a pro hledání vhodných návrhů experimentů.

In this thesis the effect of interfacial Dzyaloshinskii-Moriya-interaction (iDMI) is studied. This effect, which induces a frequency shift of spin waves with fixed wave vector, is investigated for different multilayers. Only spin waves with its wave vector perpendicular to the magnetization are detected. These spin waves are called surface waves. Brillouin light scattering (BLS) technique is used for the wave vector dependent detection of spin wave frequencies. Different setups were build and compared including a new setup, which does not use a focusing lens in front of the sample. This setup exhibits an increased wave vector resolution and simplifies changing between different samples. However, the signal intensity obtained by this setup is too low to measure spin waves under the given circumstances in reasonable time.

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