Razvoj na lipidih in talinah osnovanih sistemov polnjenih v mezoporozne nosilce za izboljšanje topnosti karvedilolaKovačević, Mila (Avtor) Zvonar Pobirk, Alenka (Mentor) German Ilić, Ilija (Komentor) lipid-based systemsSMEDDSSMEDDS granulesSMEDDS tabletsamorphous solid dispersionmesoporous carriersprecipitation inhibitorsWithin the doctoral dissertation we were focused on developing an appropriate mesoporous carriers-based delivery systems, with the aim to improve gastrointestinal solubility of carvedilol, a poorly water-soluble drug, that according to the biopharmaceutical classification belongs to group II (low solubility, high permeability). Solubility improvement was achieved by incorporation of carvedilol into a self-microemulsifying drug delivery system (SMEDDS), which was further transformed into a solid form, and by production of amorphous solid dispersions of carvedilol. Wet granulation was used for SMEDDS solidification, while solid dispersions were prepared by high-shear melt granulation and hot melt extrusion. By incorporating SMEDDS into the granules, in addition to improving the drug solubility, high liquid SMEDDS load was achieved (up to 66 % of the total granules mass). Such SMEDDS granules exhibited good flow properties, vital for further production of SMEDDS tablets or filling into capsules. Optimization of SMEDDS-based granulation dispersion, with regard to polymeric binder type and concentration, proved to be as important for achieving preferable flow properties and in vitro dissolution characteristics from SMEDDS granules. The latter were thus mixed with additional excipients and compressed into SMEDDS tablets. The tableting mixture was optimized in order to provide sufficient tablet hardness (?100 N), short disintegration time (< 3 min), while preserving self-microemulsifying properties. To prevent the drug precipitation after ingestion and keep carvedilol in dissolved state during the passage through gastrointestine, various polymeric precipitation inhibitors were added to the formulations of liquid and solid SMEDDS. Apart from SMEDDS formulation optimization, the research within the dissertation was also focused on process development within all technologies used. Ultimately, carvedilol stability was compared between produced SMEDDS granules and amorphous solid dispersions. The latter proved to be better regarding stability and achieved higher drug loading, while considering in vitro dissolution properties, SMEDDS formulations were superior.[M. Kovačević]20232023-12-23 07:15:16Doktorska disertacija153350sl