The failure of most new chemical entities to reach the market is mainly due to their drugability problems. The main causes of their drugability problem is poor bioavailability as the result of poor solubility or/and poor permeability through the GI wall. Various formulation strategies showed their capability to improve the kinetic solubility and dissolution rate of poorly water soluble drugs. The general introduction section merely focused on solid form modifications as a formulation strategy for poorly water soluble drugs. Solid dispersions are comparably discussed in detail including their preparation methods, stabilization mechanisms and the hurdles for the success of ASD in commercialized drug products with elaborate literature examples. Alternate solid forms, polymorphic forms and amorphous forms can also lead to differences in molecular, particulate and bulk level properties of the drug which can affect the bioavailability and processability of the drug. Therefore the relation of solid forms on physicochemical properties is also discussed briefly with practical examples. In addition, the solid form of drugs may also change during manufacturing which is briefly covered in the introduction section. An overview of pharmaceutical tableting, popular models to study the volume-pressure relation during compression and the mechanism and the consequences of plastic deformation of glassy polymers are also discussed.The general and specific objectives are further pointed out in chapter 2. The main objective of the project was to understand the role of compression on the structural and physical stability of amorphous solid dispersions and amorphous forms of pure drug. The glass forming properties and the glass stability of the amorphous form of pure drugs may play a role on the physical stability of amorphous solid dispersions. Indomethacin is a good glass former with relatively good physical stability. Amorphous indomethacin was prepared by cooling the molten sample rapidly (25°C/min) or slowly (0.2°C/min) to room temperature. The experimental protocols were devoid of stresses applied during sample transfer and preparation for analysis since compression and further analysis by thermal, vibrational spectroscopy and PXRD techniques were performed in the primary containers (DSC standard aluminum pan). Amorphous indomethacin generated from the gamma polymorphic form showed aging time dependent non-isothermal crystallization first predominantly to the stable gamma form and then to the metastable alfa-form of crystalline indomethacin. However, it crystallized to the stable gamma-form after a long period of storage. Compression enhanced and also increased the overall crystallization of amorphous indomethacin as evidently shown with high heat of crystallisation and lower crystallisation temperature. The tendency of crystallisation to the metastable alfa-form was higher for amorphous indomethacin prepared by fast cooling than by slow cooling from the melt. However, enthalpy recovery with physical aging was not consistently correlated with the crystallization tendency of the compressed and the uncompressed amorphous indomethacin. The origin of the selective crystallization with physical aging was not clearly understood.Unfavorable storage conditions such as elevated temperature and humidity may lead to phase transformation of solid dispersions from amorphous to crystalline or/and separation to multiple amorphous domains. Amorphous solid dispersions' success in improving bioavailability has not been reflected in the number of marketed products due to physical stability problems. Tablets are the most popular dosage forms hence most of marketed drug products of solid dispersions are tablets and capsules. Compression is an important stage of tablet manufacturing and understanding its consequences such as segmental dynamics, structural and thermodynamic changes in solid dispersions has a vital role on the quality of the final product. In chapter 4, we investigated the effect of compression on amorphous-amorphous phase separation in solid dispersions. The effect of compression was overt on the metastable amorphous solid dispersions with 30% and 40% (w/w) drug loadings in NAP ̶ PVP K 25 compositions where two distinct Tgs or a wider single Tg were observed for compressed NAP ̶ PVP ASD. These may be ascribed to the distortion of drug-polymer specific interaction as evidently shown on the IR profile. Solid dispersions with low drug loading (20% w/w) showed no difference in the glass transition and also IR profile among compressed and uncompressed samples. This indicates that the relatively stable ASD with high polymer composition can withstand the effect of compression on the drug-polymer demixing.In chapter 5 the drug-polymer mixing across different locations of laboratory spray dryers (ProCepT Micro-spray dryer and Buchi mini spray dryer B191) was investigated for various compositions of NAP ̶ PVP-VA 64 and miconazole ̶ PVP-VA 64 amorphous and partially crystalline solid dispersions. Surprisingly the drug-polymer mixing with solid dispersions varied across spray dryers. The solid dispersion with high NAP loading (50 % (w/w)) showed differences in percent crystallinity of the drug for samples collected from different locations which increased with physical aging below the Tg. Both the PXRD diffuse diffraction patterns and vibrational spectroscopic data showed differences which may arise from dissimilarities in drug-polymer mixing and level of interactions in NAP ̶ PVP-VA solid dispersions collected from different locations with spray dryers.The influence of compression was investigated for NAP/PVP-VA 64 solid dispersions collected from a single location which is covered in chapter 6. The glass transition width of the ASD was intact with compression without noticeable changes. However, a slight difference in PXRD diffuse halo diffraction pattern was observed among the compressed and uncompressed samples. The drug-polymer interaction was enhanced after compression for metastable NAP/PVP-VA amorphous solid dispersions (30% (w/w) drug loading) as revealed by FTIR which was manifested as lesser crystallinity compared to the uncompressed solid dispersions during storage. Compression led to amorphous-amorphous phase separation of NAP/PVP amorphous solid dispersion. On the contrary compression showed no clear change in drug-polymer mixing in NAP/PVP-VA ASD where the physical stability was improved for the compressed solid dispersion of NAP/PVP-VA. To understand further the role of deformation on drug-polymer interactions, we described in chapter 7 how DRS was used to probe molecular dynamics of pure PVP-VA before and after compression which will be a preliminary study to investigate the role of compression induced alterations in localised bond motions and segmental mobility with respect to drug-polymer interactions. PVP-VA showed predominant plastic deformation during tableting with low yield pressure, comparable to the most popular plastically deforming polymers used in pharmaceutical applications (e.g. MCC). Compression of PVP-VA appeared to lead to a shorter time scale for the secondary (ß) relaxation process and synchronous shift in relaxation peaks of both the localised bond motion and the segmental mobility. A similar secondary relaxation process was also observed for PVP which may indicate the source of the relaxation peak could be conformational transitions in the vinyl pyrrolidone moiety of PVP-VA. An additional wing was also identified for compressed PVP-VA with the primary relaxation peak with a mean relaxation time smaller than the powder and the slightly compressed PVP-VA. It likely suggests that compression induced heterogeneity in the segmental dynamics and also reduced the time scale of the relaxation process. The diffuse PXRD pattern of PVP-VA was markedly altered by compression as a result of a disparity in molecular packing. This study indicates that local bonds of PVP-VA involved in intermolecular interaction with NAP in the ASD can be significantly affected by compression. The general discussion with literature examples and the future perspective of the project are described in chapter 8.