20.500.12556/RUL-183341 Vpliv ovojnine, atmosfere in pogojev shranjevanja na koncentracijo kisika in pH raztopin v ampulah iz polietilena in polipropilena Impact of packaging, atmosphere and storage conditions on oxygen concentration and pH of solutions in ampoules from polyethylene and polypropylene Farmacevtska ovojnina je ključni sestavni del zdravil, saj zagotavlja stabilnost, zaščito in varnost izdelkov skozi celoten rok uporabnosti zdravila. Prehajanje kisika, ogljikovega dioksida in vlage skozi materiale primarne in sekundarne ovojnine lahko vpliva na kemično stabilnost raztopin, kar je še posebej pomembno pri vsebnikih iz polimernih materialov. Zmanjšanje oksidacije je mogoče doseči z uporabo inertne atmosfere (npr. dušik) in ustreznih kombinacij embalažnih materialov. Namen magistrske naloge je bil preučiti prepustnost ampul iz polietilena in polipropilena za kisik in ogljikov dioksid ter oceniti vpliv različnih kombinacij primarne in sekundarne ovojnine ter pogojev shranjevanja na stabilnost farmacevtskih raztopin. V okviru eksperimentalnega dela smo pripravili placebo raztopino NaCl/NaOH v vodi in jo napolnili v ampule izdelane s t.i. tehnologijo pihanja-polnjenja-zataljevanja. Del ampul smo pred polnjenjem, torej med zapiranjem prepihali z dušikom. Zavarili smo jih v polietilenske ali aluminijaste vrečke, pri čemer so bile aluminijaste vrečke pripravljene v treh različicah: vakuumsko zatesnjene, prepihane z dušikom ali zatesnjene z običajnim zrakom. Vzorce smo shranili pri sobni temperaturi in v hladilniku. V obdobju osmih tednov smo v sedmih časovnih točkah merili pH raztopine in vsebnost kisika v ampuli in v vrečki. Na podlagi izmerjenih vrednosti smo izračunali permeabilnostni koeficient kisika skozi ovojnino in primerjali rezultate med materiali in pogoji shranjevanja. Rezultati so pokazali, da so ampule iz polipropilena manj prepustne za kisik kot tiste iz polietilena, prisotnost dušikove atmosfere pa je dodatno izboljšala stabilnost vrednosti pH raztopine. Shranjevanje v hladilniku je v primerjavi s sobno temperaturo zmanjšalo prepustnost plinov. Ampule, zavarjene v aluminijaste vrečke, so izkazovale nižje koncentracije kisika in bolj stabilno vrednost pH v primerjavi s polietilenskimi vrečkami. Izračunani permeabilnostni koeficienti so bili skladni s pričakovanji in podatki proizvajalca, pri čemer je polietilen pokazal večjo prepustnost, polipropilen pa višjo odpornost proti prehodu kisika in ogljikovega dioksida. Naši rezultati kažejo, da izbira materiala za primarno in sekundarno ovojnino, ter uporaba inertne atmosfere bistveno vpliva na stabilnost farmacevtskih raztopin. Rezultati omogočajo optimizacijo izbire ovojnine za zmanjšanje oksidacije in zagotavljanje kakovosti zdravil med shranjevanjem in distribucijo. Pharmaceutical packaging is crucial, as it ensures stability, protection, and safety throughout the entire shelf life of the drug. The permeation of oxygen, carbon dioxide, and moisture through primary and secondary packaging materials can affect the chemical stability of solutions, which is particularly important for containers made of polymeric materials. Oxidation can be reduced by using an inert atmosphere (e.g., nitrogen) and right combinations of packaging materials. The aim of this thesis was to investigate the permeability of polyethylene and polypropylene ampoules to oxygen and carbon dioxide and to assess the influence of different combinations of primary and secondary packaging and storage conditions on the stability of pharmaceutical solutions. In the experimental part, a standard placebo NaCl/NaOH solution in water was prepared and filled into ampoules manufactured using blow-fill-seal technology. Some ampoules were flushed with nitrogen before filling and during sealing. They were packaged in polyethylene or aluminium bags, with the aluminium bags prepared in three variants: vacuum-sealed, nitrogen-flushed, or sealed with normal air. Samples were stored at room temperature and in a refrigerator. Over a period of eight weeks, we measured pH and oxygen content in the ampoules and bags. Based on the measured values, we calculated the oxygen permeability coefficient through the ampules and compared results between materials and storage conditions. The results showed that polypropylene ampoules were less permeable to oxygen than polyethylene ampoules, and the presence of a nitrogen atmosphere further improved solution stability. Refrigerator reduced gas permeation compared to storage at room temperature. Ampoules packaged in aluminium bags provided better protection against oxygen compared to polyethylene bags. The calculated permeability coefficients were consistent with expectations and manufacturer data, with polyethylene showing higher permeability and polypropylene having better resistance to oxygen and carbon dioxide permeation. Our findings indicate that the choice of primary and secondary packaging materials, along with the use of an inert atmosphere, significantly influences the stability of pharmaceutical solutions. These results allow for the optimization of packaging selection to minimize oxidation and ensure the quality of drugs during storage and distribution. polietilen polipropilen prepustnost plinov inertna atmosfera stabilnost farmacevtskih raztopin polyethylene polypropylene gas permeability inert atmosphere stability of pharmaceutical solutions true false false [M. Kustec] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2026-06-11 08:45:07 2026-06-11 08:45:20 2026-06-15 07:47:10 0000-00-00 00:00:00 2026 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4(043.2) 125441 281555971 32255.pdf 32255.pdf 1 17100D43109277143DD24576EF9691D5 9c5fc9a0afa16a1305138075f8a5e81e193445a3396be78079b4cc70370adb4d 18db5577-6561-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=235341 Fakulteta za farmacijo 0 0 0