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Aqueous solubility of the drug is one of the most important parameters for ensuring its absorption and therapeutic effect. Self-microemulsifying drug delivery systems (SMEDDS) are lipid formulations that improve solubility and oral bioavailability of the incorporated drugs. After redispersion in aqueous media under the influence of the gastrointestinal motility, they spontaneously form O/W microemulsions. Small droplet size has been linked with higher oral bioavailabilty. Solid dosage form is preferred due to improved stability, handling and patient compliance. SMEDDS are available on the market only in the form of the liquid SMEDDS filled into soft or hard gelatine capsules, therefore solidification of SMEDDS has been extensively investigated in the recent years. A review of different solidification techniques for production of self-emulsifying powders, granules, pellets and tablets is presented in the introduction of the thesis. Solidification requires the correct selection of excipients and setting of process parameters in order to preserve the self-emulsifying ability of the system and to obtain product suitable for further processing, i.e. filling into capsules or compression into tablets, which represents a major challenge. The aim of our research was investigation of SMEDDS% solidification techniques with large potential in pharmaceutical industry for production of solid SMEDDS (s-SMEDDS) with high drug loading, preserved self-microemulsifying (SME) properties and improved release rate and extent of poorly water soluble drug. The first part of the thesis (Chapter 1) is focused on the development and evaluation of liquid SMEDDS with improved solubility of a model poorly water soluble drug carvedilol (CARV). Further on, fluid-bed coating technology (FBC), yet poorly investigated technique for solidification of SMEDDS, was employed for transformation of CARV-SMEDDS into solid pellets. Process variables were adjusted to obtain high process yield and low pellet agglomeration. Coating process was conducted in the modified, swirl-flow based fluid bed coating device, which was proved superior over the conventional Wurster fluid bed. Addition of polymer as a binder into the coating dispersion enabled entrapping of SMEDDS in the coating layer and addition of lactose enabled higher drug loading and prevented sticking of the pellets during handling and storage. Self-microemulsifying properties as well as fast drug release were preserved in the solid products, indicating the potential of FBC as a method for production of solid SME pellets with adequate drug loading capacity and enhanced release of a poorly water-soluble drug. In Chapter 2 fluid-bed granulation (FBG), a scarcely explored SMEDDS% solidification technique, is investigated as a method for production of CARV-loaded self-microemulsifying granules. Jelena Mandić, Doctoral thesis 2 It was shown that formulation variables (type of solid carrier, optimization of granulation dispersion) and fluid-bed granulation process variables can be optimized in order to achieve suitable agglomeration process, high drug loading and appropriate product characteristics. High drug loading (64 mg CARV per g of product) was obtained and drug release from granulates was fast and complete, comparable to liquid SMEDDS and superior to crystalline carvedilol. However, products with higher drug loading had inferior flow properties, therefore a compromise has to be made. Further on, first ever published production of tablets from SME granulates, obtained with FBG, was made. Despite high content of liquid SMEDDS in entering granulate it was successfully compressed into tablets, which exhibited preserved SME properties and fast CARV release, due to the optimal excipient selection of compression mixture and compression force. In Chapter 3 solidification of CARV-SMEDDS with spray drying (SD) was conducted, using various porous silica-based carriers for achieving high SMEDDS loading (up to 67 % m/m), which can enable delivering highest dosage of CARV (25 mg) in a single dosage form (capsule). Process parameters were adjusted for obtaining high process yield, however it was also influenced by the choice of the carrier and the mixing time of dispersion before spray drying, which was attributed to more extensive absorption/adsorption of SMEDDS in the pores, when time of contact between dispersion of SMEDDS and porous carrier was longer. Products exhibited preserved self-microemulsifying properties, which, along with the presence of CARV in a molecularly dispersed form, enabled fast drug release. However, characteristics of the products (drug loading, self-microemulsifying properties and drug release rate and extent) were affected by choice of the carrier and SMEDDS:carrier ratio in solid SMEDDS. Selected s-SMEDDS, obtained with spray drying, fluid bed granulation and for comparison also direct adsorption technique, were submitted to the stability study, where decrease in content of CARV was observed. Presence of degradation products was investigated with the newly developed LC-MS method. Degradation products were characterised as amides of CARV and fatty acids present in the oil components of SMEDDS, because CARV reacted with free amine group that has nucleofilic characteristics. In s-SMEDDS, obtained with spray drying and adsorption technique, pronounced decrease in content of CARV was observed that could not be explained solely with the formation of related substances. Prefilling the pores of the carrier with API-free SMEDDS or HPMC was investigated as means of preventing partial irreversible adsorption of SMEDDS or migration of SMEDDS into the deeper regions of pores. However relative CARV content (ratio between determined amount of CARV and theoretical amount of incorporated CARV) could not have been increased by prefilling pores, which can be attributed to the deposition of pore-filling agent onto the carrier%s surface rather than in the deep pore regions. Jelena Mandić, Doctoral thesis 3 In the last chapter (Chapter 4) a condensed overview of impact of process and formulation variables on process yield and characteristics of s-SMEDDS in all solidification techniques was made. Moreover, key product characteristics were compared for all three SMEDDS% solidification techniques. This research has shown that in all studied solidification technologies, process parameters had considerable impact on process yield, as optimized conditions decreased sticking and agglomeration of the product. Formulation variables on the other hand had different impact on product characteristics, depending on the choice of technology. Nevertheless, it was demonstrated that poorly investigated, however perspective industrially applicable technologies, enable successful solidification of SMEDDS with high drug loading, preserved SME properties and fast drug release.