20.500.12556/RUL-120279 Vpliv vlage na kemijsko stabilnost omeprazola v kapsulah z zakasnelim sproščanjem magistrski študij industrijska farmacija Effect of water on the chemical stability of omeprazole delayed-release capsules Prisotnost vlage v trdnih farmacevtskih oblikah vpliva na številne kemijske, fizikalne in mikrobiološke lastnosti, kar lahko vpliva na učinkovitost, varnost in kakovost farmacevtske oblike. Omeprazol je fizikalno in kemijsko nestabilen ter tako občutljiv na številne dejavnike, kot so vlaga, povišana temperatura, kislo okolje, UV svetloba, soli in kovinski ioni. V magistrski nalogi smo preverjali vpliv vlage in temperature na kemijsko stabilnost omeprazola v kapsulah z zakasnelim sproščanjem. Preverili smo možnost napovedovanja stabilnosti s pomočjo podatkov, pridobljenih pri povišani temperaturi in/ali relativni vlažnosti. Preučili smo, kako vsebnost vode in čas izpostavljenosti stresnim pogojem vplivata na porast razkrojnih produktov. Kot glavne parametre stabilnosti smo določali vsebnost vode, vodno aktivnost ter vsoto razkrojnih produktov. Vsebnost vode smo določali s Karl Fischer titracijo, za katero smo najprej razvili ustrezno metodo in jo nato validirali. Določili smo praktične sorpcijske izoterme za vlago, ki opisujejo razmerje med vodno aktivnostjo in ravnotežno količino sorbirane vode. V ta namen smo tudi razvili in validirali metodo za določanje vodne aktivnosti. Iz znane sestave pelet in pridobljenih sorpcijskih izoterm za zdravilno učinkovino in pomožne snovi smo izračunali teoretično sorpcijsko izotermo in jo primerjali z izmerjeno. Opazili smo manjša odstopanja, ki so posledica kompleksnosti farmacevtske oblike. Ugotovili smo, da povečanje količine vlage v farmacevtski obliki vpliva na porast razkrojnih produktov. Iz primerjave različno posušenih kapsul pred pakiranjem v ovojnino smo ugotovili, da je farmacevtska oblika stabilnejša v primeru, ko je začetna vsebnost vode nižja. Pokazali smo, da higroskopnost zdravilne učinkovine vpliva na njeno kemijsko stabilnost v peletah z zakasnelim sproščanjem, pakiranih v trde želatinaste kapsule. Napovedovanje stabilnosti smo izvedli s pomočjo izračuna, ki temelji na prilagojeni Arrheniusovi enačbi s členom za vlago, prepustnosti ovojnine za vlago in sorpcijsko-desorpcijskega prenosa vlage med komponentami v ovojnini. The presence of moisture in solid dosage forms affects numerous chemical, physical and microbiological properties. This can affect their effectiveness, safety, and quality. Omeprazole is a proton pump inhibitor, which effectively inhibits secretion of stomach acid and has a long-lasting effect. Omeprazole molecule is physically and chemically unstable, therefore it is sensitive to numerous factors such as moisture, elevated temperature, acidic environment, UV light, salts and metal ions. In the Master’s thesis, the effect of moisture and temperature on the chemical stability of omeprazole delayed-release capsules was evaluated. The possibility to predict stability with the help of information, obtained at elevated temperature and/or relative humidity was tested. In addition, the effect of water content and the time of exposure to the test conditions (temperature and relative humidity) on the increase of degradation products was studied. Water content, water activity and the sum of degradation products were determined as main stability parameters. Water content was determined with the Karl Fischer titration, for which a suitable method was first developed and then validated. Furthermore, the practical moisture sorption isotherm, which describes the relationship between water activity and equilibrated amount of absorbed water, was determined. For this purpose, a method for the determination of water activity was developed and validated. From known compositions of pellets and obtained sorption isotherms for active pharmaceutical ingredient and excipients, a theoretical sorption isotherm was calculated and compared with the practical sorption isotherm. Minor deviations between two isotherms were result of dosage forms complexity. Elevated levels of moisture in dosage form affected the increase of degradation products. Comparison of differently dried capsules before packaging revealed that dosage forms with a low starting water content were more stable. In the research was shown that the hygroscopicity of the active pharmaceutical ingredient affects its chemical stability in delayed-release pellets, packed in hard gelatin capsules. The prediction of stability was performed with a calculation, based on humidity-corrected Arrhenius equation, moisture vapor transmission rate (MVTR) and sorption-desorption moisture transfer (SDMT) between components in packaging. omeprazol kemijska stabilnost napovedovanje stabilnosti validacija true false false [D. Smodiš] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2020-09-17 13:18:22 2020-09-17 13:18:23 2022-09-01 03:58:14 0000-00-00 00:00:00 2018 0 Ljubljana 2018 Ljubljana IX, 67 f. 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 661.12:615.45(043.3) 4646513 MAG_Smodis_David_2018.pdf MAG_Smodis_David_2018.pdf 1 9FDA2152DBE40E04D217065DDA5EF2E2 6db7433701585cf28f078438d5d1dcb85acfbe6c5d4838b3983a6d5080c0dcde 0c2bef98-a1ba-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=135066 Fakulteta za farmacijo 0 0 0