20.500.12556/RUL-150947 Liofilizacija nanostrukturiranih lipidnih nosilcev s težko topno učinkovino Lyophilization of nanostructured lipid carriers with poorly soluble drug Z razvojem dostavnih sistemov lahko izboljšamo biološko razpoložljivost novih zdravilnih učinkovin, ki so pogosto težko topne. Sodobni nanodostavni sistemi lahko zaobidejo slabosti že znanih koloidnih dostavnih sistemov in omogočajo tarčno delovanje, prirejeno sproščanje in višjo učinkovitost vgradnje. V magistrski nalogi smo težko topno modelno učinkovino A vgradili v nanostruktrurirane lipidne nosilce (NLN) in jim po pripravi ter shranjevanju vrednotili velikost, polidisperzni indeks, zeta potencial, učinkovitost vgradnje in dejansko vsebnost. NLN so bili izdelani z visokostrižno homogenizacijo, vsebovali pa so trdni lipid Compritol 888 ATO, stabilizatorja PEG2000-DSPE in Poloxamer 188, tekoči lipid Captex 200 ter modelno učinkovino A. Izdelali smo 149,17 ± 8,35 nm velike NLN z učinkovitostjo vgradnje 80,62 ± 3,03 % in dejansko vsebnostjo 1,96 ± 0,06 %. Količina vgrajene modelne učinkovine A se je po pripravi NLN hitro zmanjševala, zato smo se odločili, da sestavo in pripravo optimiziramo. V optimizaciji smo proučili (i) vpliv dodatka antioksidanta BHA in (ii) shranjevanje vzorcev pri različnih temperaturnih pogojih. Ker je vzorec med shranjevanjem podvržen številnim fizikalnim in kemijskim spremembam, smo v optimizaciji izdelave NLN odstranili vodo iz disperzije s sušenjem v sušilniku in liofilizatorju. Postopek liofilizacije smo naknadno optimizirali z (i) dodatkom različnih polimerov, (ii) z uporabo različnih načinov zamrzovanja vzorcev pred liofilizacijo in (iii) z različnimi pristopi redispergiranja liofiliziranih vzorcev. Z liofilizacijo smo iz disperzije NLN pripravili suh prah, ki smo ga po redispergiranju ponovno vrednotili in shranjevali. Optimiziran vzorec, ki smo ga pripravili iz disperzije NLN z dodatkom polietilenglikola 6000, smo zamrznili v tekočem dušiku, ga liofilizirali ter redispergirali s prečiščeno vodo s pomočjo vorteks mešala. Optimiziran vzorec, P6000-LTD, ima od izhodiščne formulacije NLN25 °C večje NLN in približno 7 % višjo učinkovitostjo vgradnje zdravilne učinkovine. Kljub številnim eksperimentom ugotavljamo, da liofilizacija ni primerna rešitev za optimiziranje pripravljenih NLN, zato bi morali stabilnost NLN izboljšati z drugimi pristopi. By developing new delivery systems, we can improve the bioavailability of new active ingredients, which are often poorly soluble. New nanodelivery systems can overcome the limitations of already known colloidal delivery systems and enable targeted delivery, controlled release, and improved encapsulation efficiency. In this master's thesis, we incorporated poorly soluble model active ingredient A into nanostructured lipid carriers (NLCs) and evaluated the observed parameters such as size, polydispersity index, zeta potential, encapsulation efficiency and drug loading after preparation and storage. NLCs were prepared by high-shear homogenization and contained the solid lipid Compritol 888 ATO, the stabilizers PEG 2000-DSPE and Poloxamer 188, the liquid lipid Captex 200, and model active ingredient A. We prepared 149.17 ± 8.35 nm NLC with an encapsulation efficiency of 80.62 ± 3.03% and drug loading of 1.96 ± 0.06%. The amount of incorporated model active ingredient A decreased rapidly after the preparation of NLC, which prompted us to optimize the composition and preparation process. During the optimization, we investigated (i) the influence adding the antioxidant BHA and (ii) the effect of different storage conditions. Because the sample underwent numerous physical and chemical changes during storage, we removed water from the dispersion by drying it in a dryer and freeze-dryer as part of the manufacturing optimization process. The lyophilization process was further optimized by (i) adding different polymers, (ii) different freezing methods prior to the lyophilization process, and (iii) using different approaches to redisperse the lyophilizates. With lyophilization, we prepared a dry powder from the NLC dispersion, which was evaluated and stored after redispersion. The optimized sample prepared from the NLC dispersion with the addition of polyethylene glycol 6000 was frozen in liquid nitrogen, lyophilized and redispersed with purified water using a vortex mixer. The optimized P6000-LTD sample had a larger NLC and approximately 7% higher encapsulation efficiency than the initial formulation NLN25 °C. Despite conducting numerous experiments, it is our conclusion that lyophilization is not a suitable approach for optimizing the produced NLC. We believe it is imperative to explore alternative approaches to enhance the stability of the NLC. nanostrukturirani lipidni nosilci težko topna učinkovina stabilnost liofilizacija nanostructured lipid carriers poorly water-soluble drug stability lyophilization true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2023-09-26 08:45:30 2023-09-26 08:45:34 2023-09-27 03:59:25 0000-00-00 00:00:00 2023 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 2024-09-25 101635 18398.pdf 18398.pdf 1 087532388FA6985CB326AE50F1C93DF4 26213cfae670ac2967dea337b3ee9fb49941ec52c5ff4351cdaffabecdacb210 4b77fb02-5c38-11ee-9c9a-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=175820 Fakulteta za farmacijo 0 0 0