Vrednotenje stabilnosti vitaminov A in D3 v raztopinah in polimernih nanovlaknih

Gorjup, Nana (author), Roškar, Robert (mentor), Kocbek, Petra (co-mentor)

Vitamini so nujno potrebni za normalno delovanje našega telesa. Njihova uporaba se je razširila tudi v dermatologiji, kjer za zdravljenje luskavice uporabljamo derivate lipofilnih vitaminov A in D. Za lokalno zdravljenje luskavice uporabljamo tudi salicilno kislino, ki je, glede na razpoložljive podatke, nezdružljiva z derivati vitamina D. V magistrski nalogi smo proučevali stabilnost lipofilnih vitaminov D3, A in A acetata. Naš namen je bil ovrednotiti njihovo stabilnost v različnih vodnih medijih (pitna, destilirana in ultra čista voda), preveriti, ali salicilna kislina destabilizira vitamin D3, in kako izbrani antioksidanti (vitamin E in butilhidroksitoluen) stabilizirajo izbrane vitamine. Za vrednotenje stabilnosti smo uporabili vpeljano metodo tekočinske kromatografije visoke ločljivosti. Z namenom povečanja stabilnosti vitaminov smo jih vgradili v polimerna nanovlakna, ki smo jih izdelali z elektrostatskim sukanjem. Z uporabo vrstične elektronske mikroskopije smo proučevali morfološke lastnosti izdelanih nanovlaken. Preverili smo tudi uspešnost vgradnje vitaminov, na osnovi konstant hitrosti razgradnje pa ovrednotili učinek stabilizacije vitaminov v nanovlaknih v primerjavi z njihovo stabilnostjo v vodnih raztopinah. Ugotovili smo, da so vsi trije vitamini zelo nestabilni v vodnih raztopinah, najmanj stabilen je vitamin A in najbolj vitamin D3. Potrdili smo tudi destabilizacijski učinek salicilne kislina na vitamin D3 ter z izbranimi antioksidanti (vitamin E in butilhidroksitoluen) povečali stabilnost proučevanih vitaminov v raztopinah. Potrdili smo kratkoročno stabilnost vitaminov v različnih organskih topilih in v polimerni raztopini za elektrostatsko sukanje ter določili izkoristek vgradnje vitaminov, na podlagi katerega smo zaključili, da sta vitamin D3 in vitamin A acetat primerna, vitamin A pa je manj primeren za vgradnjo v nanovlakna. Z opazovanjem morfoloških lastnosti nanovlaken smo ugotovili, da imajo široko porazdelitev debelin, kar je smiselno v prihodnje optimizirati. V dolgoročni stabilnostni študiji sedmih izdelanih formulacij nanovlaken smo z vgradnjo vitaminov v nanovlakna povečali njihovo stabilnost. Salicilna kislina je tudi v nanovlaknih destabilizirala vitamin D3, vendar v veliko manjšem obsegu kot v vodnih raztopinah. Z dodanimi antioksidanti smo stabilnost vitaminov v nanovlaknih povečali. V zaključku smo s primerjavo konstant hitrosti razgradnje potrdili, da smo z vgradnjo vitaminov v nanovlakna uspeli znatno povečati njihovo stabilnost (od približno stokrat do nekaj tisočkrat), kar je bil naš osrednji namen.

• Language: Slovenian
• Keywords: vitamin D3, vitamin A, stabilizacija, nanovlakna, HPLC
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2019
• PID: 20.500.12556/RUL-112549
• Publication date in RUL: 24.10.2019

Secondary language

• Language: English
• Title: Evaluation of vitamins A and D3 stability in solutions and polymer nanofibers

Abstract

Vitamins are essential for the normal function of human body. Their usage has also spread in dermatology, where derivatives of lipophilic vitamins A and D are used for psoriasis treatment. For the local treatment of psoriasis, salicylic acid is also used, which is considered incompatible with vitamin D derivatives. In this thesis, the stability of the lipophilic vitamins D3, A and A acetate was investigated. The aim was to evaluate their stability in various aqueous media (tap, distilled and ultra-pure water), to verify the destabilizing effect of salicylic acid on vitamin D3, as well as the stabilizing effect of selected antioxidants (vitamin E or butylhydroxytoluene) on the tested vitamins. Previously developed and verified high-performance liquid chromatography method was used for their stability evaluation. In order to increase vitamins stability, they were incorporated into polymeric nanofibers, prepared by electrospinning. The nanofibers were evaluated in terms of their morphological properties by scanning electron microscopy. The vitamin incorporation efficiency was also determined. The stability of the vitamins was evaluated based on first order reaction rate constants, which were compared between nanofibers and their correlating aqueous solutions. All three vitamins were highly unstable in aqueous solutions; however, vitamin A was found to be most unstable and vitamin D3 most stable among them. Vitamin D3 was found unstable in the presence of salicylic acid, whereas all vitamins exhibited increased stability in the presence of selected antioxidants (vitamin E and butylhydroxytoluene). After confirming the short-term stability of vitamins in various organic solvents and solutions for electrospinning, the selected vitamins were incorporated into polymer nanofibers. Based on incorporation efficiency vitamin D3 and vitamin A acetate were shown to be suitable for incorporation in nanofibers, whereas vitamin A was shown to be less suitable. Investigation of nanofiber morphology revealed a wide size distribution, which requires further optimization. The most important findings after long-term stability study of the seven formulations of nanofibers are the following: incorporation of vitamins in nanofibers increases their stability; the destabilizing effect of salicylic acid on vitamin D3 is much lower in nanofibers compared to the aqueous solutions; and addition of antioxidants further improves the stability of vitamins in this system. Based on the reaction rate constants, it can be concluded that incorporation of vitamins in nanofibers increases their stability from about a hundred times to several thousand times.

• Keywords: vitamin D3, vitamin A, stabilization, nanofibers, HPLC