Faculty of Pharmacy, Lj. (FFALJ)
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Uporaba mikrokalorimetrije pri vrednotenju stabilnosti zdravilnih učinkovin in farmacevtskih oblik na primeru nekaterih zaviralcev angiotenzinske konvertaze = The use of microcalorimetry for stability evaluation of active substances and drug products containing some angiotensin convertaze inhibitors : doktorska disertacijaSimončič, ZvoneProučevane zdravilne učinkovine enalapril (EM), cilazapril (CIL) in ramipril (RAM) pripadajo skupini inhibitorjev angiotenzinske konvertaze (ACE inhibitorji). V študijah smo poleg omenjenih ... zdravilnih učinkovin uporabili tudi strukturno sorodno zdravilno učinkovino xPRIL. Vse štiri navedene modelnespojine smo za naše študije izbrali na osnovi njihovih različnih strukturnih in posledično fizikalno-kemijskih značilnosti. ACE inhibitorji razpadajo preko dveh glavnih razgradnih poti. Prva je hidroliza estra, druga pa je intramolekularna ciklizacija, ki vodi do nastanka diketopiperazinskega derivata (DKP), ki ima zaradi svoje strukture lipofilne lastnosti. Za ovrednotenje stabilnostnih lastnosti modelnih zdravilnih učinkovin v vodnih raztopinah smo uporabili metodo izotermne mikrokalorimetrije (MC), pridobljene rezultate pa smo primerjalno ovrednotili s podatki, pridobljenimi s stabilnostno indikativnimi HPLC metodami. Pri delu smo ovrednotili karakteristični vrh, ki smo ga opazili na termičnih diagramih pri vzorcih raztopin ACE inhibitorjev s pH 2.0 (v nekaterih primerih tudi pri pH 6.8). Predvidevali smo, da ta vrh pripada ločitvi faz, ko se lipofilni DKP v obliki kapljic izloči iz vodne raztopine. Z metodo masne spektrometrije (MS) smo potrdili identiteto DKP v izločenih kapljicah, z različnimi poizkusi z metodo MC pa potrdili le-to kot stabilnostno indikativno in predvsem hitro ter enostavno metodo za ugotavljanje zaporedja ACE inhibitorjev glede na stabilnostne lastnosti. V drugem delu študije smo poiskali omejitve oz. lastnosti posameznih vzorcev, na katere moramo biti pri vrednotenju MC rezultatov še posebej pozorni.Type of material - dissertationPublication and manufacture - Ljubljana : [Z. Simončič], 2009Language - slovenianCOBISS.SI-ID - 2514289
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Digitalna knjižnica Slovenije - dLib.siDostop z namenskih računalnikov v prostorih NUK
Author
Simončič, Zvone
Other authors
Kmetec, Vojko |
Kogej, Ksenija
Topics
stabilnost zdravil |
analizne metode |
izotermna kalorimetrija |
ACE inhibitorji |
formulacijske študije
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Knjižnica dr 0000000543 SIMONČIČ ZVONE Uporaba IN: 0010541 Knjižnica dr 543 SIMONČIČ ZVONE Uporaba IN: 0010541 |
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Simončič, Zvone | 24524 |
Kmetec, Vojko | 01466 |
Kogej, Ksenija | 04614 |
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