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Vrednotenje stabilnosti in sproščanja askorbilpalmitata iz lamelarnih tekočih kristalov
ID Lunar, Nastja (Author), ID Gosenca Matjaž, Mirjam (Mentor) More about this mentor... This link opens in a new window, ID Roškar, Robert (Co-mentor)

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Abstract
Lamelarni tekoči kristali zaradi svoje strukture in lastnosti predstavljajo fiziološko sprejemljiv dostavni sistem za dermalno uporabo, v katerega lahko vgradimo lipofilne, hidrofilne ali amfifilne spojine. Askorbilpalmitat je znan antioksidant, ki se pogosto uporablja v farmaciji in kozmetiki. Je zelo občutljiva in nestabilna amfifilna snov, katere razpad povzročijo številni dejavniki, kot so svetloba, kisik, vlaga ali neustrezna sestava formulacije. V prvem delu magistrske naloge smo ovrednotili stabilnost askorbilpalmitata, vgrajenega v osem sistemov tekočih kristalov (TK 1-TK 8), s konstantnim razmerjem lipofilnih in površinsko aktivnih snovi ob naraščajočem deležu vode kot hidrofilne faze. Preden smo vzorce tekočih kristalov z vgrajenim askorbilpalmitatom izpostavili staranju, smo nadgradili že obstoječo HPLC metodo za analizo askorbilpalmitata. HPLC metodo smo ustrezno optimizirali in validirali, in sicer z vidika selektivnosti, ponovljivosti, točnosti, linearnosti in stabilnosti. Nadalje smo v okviru 56-dnevne pospešene stabilnostne študije ugotovili, da stabilnost askorbilpalmitata z večanjem deleža vode v sistemih tekočih kristalov pada. Sistemi tekočih kristalov z manjšim deležem vode so bili stabilnejši (TK 1-TK 5) glede na sisteme z večjim deležem vode (TK 6-TK 8). Po 28 dneh shranjevanja pri 40 °C in 75 % relativni vlažnosti je bil askorbilpalmitat najbolj stabilen, ko je bil vgrajen v TK 1 (20 % (m/m) vode v sestavi), najmanj pa v sistemu TK 8 (55 % (m/m) vode v sestavi). Na podlagi izračunanih konstant reakcijske hitrosti in R2 smo ugotovili, da kinetika kemijskih reakcij razgradnje askorbilpalmitata sledi 1. redu. Iz vrednosti konstant reakcijske hitrosti je bila razvidna padajoča stabilnost od TK 1 (0,023 d-1) proti TK 8 (0,043 d-1), saj se je z večanjem deleža vode konstanta večala. V drugem sklopu naloge smo vrednotili in vitro sproščanje askorbilpalmitata iz izbranih sistemov tekočih kristalov skozi umetno membrano s pomočjo Franz-ovih difuzijskih celic. Predpostavili smo, da bo sproščanje odvisno od notranje strukture in viskoznosti sistemov, kar se spreminja glede na delež vode. Hitrejše sproščanje in v večjem obsegu smo tako potrdili za sisteme TK 1-TK 4, ki imajo manjši delež proste vode v interlamelarnem prostoru in tako manjše razdalje med lamelami, v primerjavi s TK 5-TK 8, kjer se zaradi naraščajočega deleža vode razdalje med lamelami večajo ob sočasni prisotnosti micelov. Zaključili smo, da lahko tekoče kristale uporabljamo kot dostavne sisteme za podaljšano sproščanje in da le-ti predstavljajo obetaven dostavni sistem za dermalno aplikacijo askorbilpalmitata.

Language:Slovenian
Keywords:askorbilpalmitat, lamelarni tekoči kristali, stabilnost, sproščanje, HPLC metoda
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2020
PID:20.500.12556/RUL-117299 This link opens in a new window
Publication date in RUL:04.07.2020
Views:1499
Downloads:318
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Secondary language

Language:English
Title:Evaluation of ascorbyl palmitate stability and release profile from lamellar liquid crystals
Abstract:
Lamellar liquid crystals have been due to their unique structure and properties used as dermal delivery system for lipophilic, hydrophilic or amphiphilic compounds. Ascorbyl palmitate is a well-known antioxidant that is widely used in pharmacy and cosmetics. It is considered as a very unstable amphiphilic compound, which degrades under the influence of light, oxygen, temperature, humidity as well as in suboptimal formulations. In the first part of the thesis we evaluated the stability of ascorbyl palmitate incorporated in eight different systems of liquid crystals (TK 1-TK 8), with a constant ratio of lipophilic compounds and surfactants and with increasing water content as hydrophilic compound. Before the stability study the present HPLC method for ascorbyl palmitate determination was upgraded. Namely, the method was optimized and validated by evaluating the selectivity, repeatability, accuracy, linearity and stability. Further, as a part of the 56-day study we showed that the stability of ascorbyl palmitate was decreasing with increased water content in liquid crystals. Stability of ascorbyl palmitate was better in liquid crystals with lower water content (TK 1-TK 5) compared to liquid crystals with higher water content (TK 6-TK 8). After 28 days of storage at 40 °C and 75 % relative humidity TK 1 (20 % (w/w) of water content) was the most stable system and TK 8 (55 % (w/w) of water content) was considered to be the least stable system. Based on calculated reaction rate constants and R2 we determined that kinetics of chemical reactions of ascorbyl palmitate follows 1. order. Values of the reaction rate constants showed a decreasing stability from TK 1 (0,023 d-1) to TK 8 (0,043 d-1) as the constant increased with increasing water content. In the second part of the thesis we evaluated in vitro release of ascorbyl palmitate from eight systems of liquid crystals. The study was performed on an artificial membrane using Franz diffusion cells. We assumed that the release would depend on the internal structure and viscosity of the systems, which varies with the proportion of water. Therefore, a faster release and to a greater extent was confirmed for systems TK 1-TK 4, which contained smaller amounts of free water in the interlamellar spacing and thus shorter distances between lamellaes, compared to systems TK 5-TK 8, where due to increasing water content the distances between lamellaes are increasing in the presence of micelles. We concluded that liquid crystals can be used as delivery system for sustained release and that they show a great potential as dermal delivery system.

Keywords:ascorbyl palmitate, lamellar liquid crystals, stability, release, HPLC method

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