| Summary: | The project started with studying the unique characteristics of the zwitterionic drug (norfloxacin), considered as an example of very slightly water soluble drug. The study focused on the effects of its chemical structure on its interaction with surfactants (PEG200 and Synperonic TM PE/L-61) in liquisolid systems and, consequently, on its release into water dissolution medium. The next stage was an approach to solve the problems of the dissolution, compressibility and flowability of norfloxacin liquisolid formulations through adding water as a liquid binder to make wet granulated liquisolid formulations. The water in the liquisolid formulations works as a liquid binder to the carrier and coating particles, creating a wider space inside their structure, which allows the amount of the liquid vehicle (PEG200 and Synperonic TM PE/L-61) to increase inside the formulations. This feature reflects positively on the flowability (decreasing the angle of the slide), compressibility (increasing the load factor) and the dissolution behaviour of norfloxacin (increasing drug release to more than 20%). Another liquid binder (PVP) was used in the wet granulations and a comparison was made between PVP solutions, water and classical liquisolid formulations in terms of dissolutions, flowability, compressibility, DSC thermographs and FTIR spectra. The successful application of wet granulation techniques with liquisolid formulations was tested with a very hydrophobic drug (cinnarizine). Due to its hydrophobicity, traditional mixing of surfactants and the drug particles did not improve its dissolution in water medium, although the solubility was relatively high. ii The methodology was again applied to investigate how the dissolution of cinnarizine altered with several different types of surfactants. The results lead to a change from traditional mixing to a self-nano emulsifying drug delivery system (SNEDD). Optimization to select a suitable oil (Capmul® MCM EP), surfactant (Kolliphor® RH40) and co-surfactant (PEG400) was found to depend initially on the solubility of cinnarizine. Further optimisation identified the relative percentages (66.6:16.6:16.6 for oil, surfactant and co-surfactant, respectively) and the drug concentration required for the SNEDD (6.0% w/w) was found to depend on the mixture experimental design, using dissolution trends as an indicator. Finally, the selected SNEDD system was converted to a liquisolid system using the water granulation technique to make tablets with acceptable compressibility and flowability. Due to the negative effect of coating material (Cab-O-Sil® M-5P) on the dissolution behaviour, a new method was developed to determine the compressibility load factor using a central composite design and response surface methodology. The predicted model was validated and the accuracy was over 95%, allowing it to be used for preparation of the SNEDDs. The new preparations were compared to tablets from the commercial sources. The new formulations show significant enhancement in the percentage of the drug releases in distilled water dissolution medium.
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