<p>Uloga micela u razvoju farmaceutskih oblika zasniva se na njihovom potencijalu da kao transportni sistemi povećaju bioraspoloživost lekovite supstance i unaprede njen farmakokinetski profil. Micele mogu da modifikuju propustljivost biološkuh membrana, omoguće kontrolisano oslobađanje lekovite supstance iz farmaceutskog oblika, stabilizuju lekovitu supstancu, itd. Kombinovanje različitih surfaktanata kao gradivih jedinica omogućava konstruisanje micela sa poželjnim fizičko-hemijskim karakteristikama. Takođe, mešovite micele između čijih gradivnih jedinica postoje sinergističke interakcije se formiraju na nižim koncentracijama surfaktanata u poređenju sa monokomponentnim micelama. U doktorskoj disertaciji je ispitana termodinamička stabilnost binarnih mešovitih micela Brij S10 i Brij S20 surfaktanata sa polisorbatom 20, polisorbatom 60 i polisorbatom 80 kao kosurfaktantima. Analiziran je uticaj građe odabranih nejonskih surfaktanata na fizičko-hemijske parametre i stabilnost njihovih mešovitih micela. Vrednosti kritične micelarne koncentracije su dobijene spektrofluorimetrijskim merenjima. Da bi se analizirao uticaj temperature na termodinamičku stabilnost micela, merenja su vršena na sledećim temperaturama: 273.15 K, 283.15 K, 293.15 K, 303.15 K i 313.15 K. Rezultati su tumačeni sa aspekta teorije regularnih rastvora (regular solution theory – RST), uz primenu Porterove jednačine. Na osnovu rezultata istraživanja, predloženi su modeli monokomponentnih i binarnih mešovitih micela. Utvrđeno je da u svim analiziranim binarnim mešovitim sistemima postoji dodatna entropija. Može se doneti zaključak da pretpostavka RST o isključivo entalpijskoj prirodi dodatne Gibsove energije nije primenljiva na ispitivane binarne sisteme. Utvrđeno je da postojanje razlike u dužini hidrofobnih segmenata monomera dodatno stabilizuje mešovitu micelu. Sa porastom temperature, ovaj stabilizacioni efekat entropijskog porekla postaje izraženiji. Prisustvo dvostruke veze u ugljovodoničnom lancu polisorbata 80 doprinosi povećanoj rigidnosti njegovih molekula. Rezultat je smanjena termodinamička stabilnost mešovitih micela koje sadrže polisorbat 80 u poređenju sa mešovitim micelama koje sadrže njegov zasićeni homolog, polisorbat 60. Utvrđeno je da razlika u dužini polarnih segmenata monomera koji grade mešovitu micelu utiče na stepen hidratacije micele, a time i na njenu stabilnost.</p> / <p>The role of the micelles in pharmaceutical formulation lies in their ability to, when used as drug delivery systems, increase the bioavailability of the drug and enhance its pharmacokinetic profile. Micelles may modify the permeability of biomembranes, enable controlled release from drug delivery systems, stabilize the drug, etc. By combining different surfactants as building units it is possible to engineer micelles with favorable physicochemical characteristics. Also, the mixed micelles between whose building units synergistic interactions exist are formed on lower concentrations of surfactants in comparison to single-component micelles. In the doctoral dissertation the thermodynamic stability of binary mixed micelles built of Brij S10 and Brij S20 with polysorbate 20, polysorbate 60 and polysorbate 80 as co-surfactants is examined. The influence of the structure of selected nonionic surfactants on physicochemical parameters and the stability of their mixed micelles is analyzed. Critical micelle concentration values were obtained by spectrofluorimetric measurements. In order to analyze the influence of the temperature on the micelles’ thermodynamic stability, measurements were conducted on following temperatures: 273.15 K, 283.15 K, 293.15 K, 303.15 K and 313.15 K. Obtained results were studied using regular solution theory (RST) and Porter’s equation. Based on the research results, models of both single-component and binary mixed micelles are introduced. It is deduced that in all analyzed binary mixed systems the excess entropy exists. A conclusion can be made that the assumption of RST regarding solely enthalpic nature of the excess Gibbs energy is not applicable to investigated binary systems. The difference in the length of the hydrophobic segments of monomers additionally stabilizes the mixed micelle. With the increase in the temperature, this stabilizing effect of the entropic nature is more noticeable. The existence of the double bond in polysorbate 80 hydrocarbon chain contributes to the increased rigidity of its molecules. As a result, the thermodynamic stability of the mixed micelles containing polysorbate 80 is lesser than the stability of the mixed micelles containing its saturated homologue, polysorbate 60. It is determined that the difference in length of polar segments of mixed micelle monomers affects the micelle hydration and therefore, its stability.</p>
| Identifer | oai:union.ndltd.org:uns.ac.rs/oai:CRISUNS:(BISIS)104920 |
| Date | 18 October 2017 |
| Creators | Obradović Stoja |
| Contributors | Poša Mihalj, Tepavčević Vesna, Sakač Marija, Bećarević Mirjana, Milić Nataša |
| Publisher | Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, University of Novi Sad, Faculty of Medicine at Novi Sad |
| Source Sets | University of Novi Sad |
| Language | Serbian |
| Detected Language | English |
| Type | PhD thesis |
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