TY  - THES
AU  - Grujić, Maja
PY  - 2020
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7654
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:22810/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=23030537
UR  - https://nardus.mpn.gov.rs/handle/123456789/17521
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3724
AB  - Protolitičke ravnoteže sartana (irbesartana, losartana i valsartana) ispitane su bez i u prisustvu surfaktanata različitog naelektrisanja: anjonskog (natrijum-dodecilsulfat ˗ SDS), katjonskog (cetiltrimetilamonijum-bromid ˗ CTAB) i nejonskih (4-oktilfenolpolietoksilat ˗ TX-100 i polioksietilen (23) lauril etar ˗ Brij 35).Sartani su antagonisti angiotenzinskih AT1 receptora koji se koriste u terapiji hipertenzije, srčane insuficijencije i dijabetičke nefropatije. Fizičko-hemijski parametri lekova pKa i rastvorljivost, neophodni za procenu farmakološkog i farmakokinetikog ponašanja, u biosredini mogu imati različite vrednosti u poređenju sa “čisto” vodenom sredinom. Ispitivanjem ovih parametara u uslovima koji su sličniji fiziološkim, stiče se bolji uvid u jonizaciju i rastvorljivost lekova u biosredini. Kao pojednostavljeni simulirajući sistemi za biomembrane u ovom radu su korišćeni rastvori surfaktanata čije micele podražavaju osnovne strukturne i funkcionalne karakteristike biomembrana.U hemijskom pogledu, irbesartan i losartan su amfoliti koji sadrže jedan kiseli centar (tetrazol) i jedan bazni centar (imidazol), dok valsartan sadrži dva kisela centra (tetrazol i karboksilna grupa). Jonizacione konstante su određene potenciometrijski pri konstantnoj jonskoj sili (0,1 M NaCl) i temperaturi 25°C, bez i u prisustvu surfaktanata. Potenciometrijski podaci analizirani su primenom kompjuterskog programa Hyperquad. Zbog male rastvorljivosti sartana u vodi, pKaw vrednosti koje odgovaraju „čisto“vodenoj sredini (bez prisustva surfaktanata) dobijene su ekstrapolacijom praktičnih pKa* vrednosti određenih u smešama metanola i vode, različitog odnosa. Zbog solubilizirajućih efekata surfaktanata, za određivanje jonizacionih konstanti u micelarnoj sredini nisu korišćeni korastvarači.Uticaj surfaktanata na protolitičke ravnoteže procenjen je na osnovu pomeranja pKaapp vrednosti određenih u micelarnoj sredini u odnosu na pKaw vrednosti određenih u „čisto“ vodenoj sredini. U prisustvu anjonskih SDS micela došlo je do porasta pKaapp vrednosti sartana (do +1,72 pK jedinice), dok je u prisustvu katjonskih CTAB micela uočen suprotan efekat i smanjenje pKaapp vrednosti (do -1,44 pK jedinice). Na osnovu rezultata ove studije pretpostavljeno je da su jonizujući centri ispitanih sartana uključeni u elektrostatičke interakcije sa površinskim Sternovim slojem jonskih micela. Pomeranje pKaapp vrednosti pod uticajem nejonskih surfaktanata (od -0,86 do +1,30) posledica je interakcija sartana sa hidrofilnim, palisadnim slojem nejonskih TX-100 i Brij 35 micela. Najveće promene u dijagramima raspodele ravnotežnih oblika ispitanih sartana u prisustvu micela (od -44% do +80%) uočene su na biofarmaceutski značajnoj pH vrednosti 4,5 (odgovara pH vrednosti u proksimalnom delu tankog creva) i mogu se razmatrati u kontekstu potencijalnog uticaja na intestinalnu apsorpciju i bioraspoloživost.Teorijska studija je izvedena sa ciljem da se stekne bolji uvid u preklopljene protolitičke ravnoteže irbesartana, losartana i valsartana, kao i u interakcije njihovih ravnotežnih oblika sa micelama kao simulirajućim sistemima biomembrana. S obzirom na prisustvo dva jonizaciona centra u molekulu ispitivanih sartana i na bliske vrednosti njihovih jonizacionih konstanti, u teorijskoj studiji ispitani su redosled jonizacije irbesartana, losartana i valsartana u vodenoj sredini, kao i mogući načini interakcije njihovih ravnotežnih oblika sa micelama surfaktanata...
AB  - Protolytic equilibria of sartans (irbesartan, losartan, and valsartan) were investigated with and without the presence of differently charged surfactants: anionic (sodium dodecyl sulfate ˗ SDS), cationic (cetyltrimethylammonium bromide ˗ CTAB), and nonionic (4-octylphenol polyethoxylate – TX-100 and polyoxyethylene (23) lauryl ether – Brij 35).Sartans are angiotensin AT1 receptor antagonists used in therapy of hypertension, heart failure, and diabetic nephropathy. The most important physicochemical properties of drugs, the pKa values and solubility, necessary for estimation of pharmacological and pharmacokinetic behavior, may have different values in bioenvironment as compared to the "pure" aqueous solution. By examining these parameters under conditions more similar to physiological ones, a better insight in in vivo ionization and solubility of drugs could be achieved. In this work, micellar solutions of surfactants were used as a simplified biomembrane mimetic systems, because of their nature to mimic the most essential structural and functional properties of biomembranes.From the chemical point of view, irbesartan and losartan are ampholytes containing one acidic center (tetrazole) and one basic center (imidazole), whereas valsartan contains two acidic centers (tetrazole and carboxyl group). The ionization constants were determined potentiometrically at a constant ionic strength (0.1 M NaCl) and temperature 25 °C, with and without the presence of surfactants. Potentiometric data were analyzed using the computer program Hyperquad. Due to the poor water solubility of sartans, the pKaw values, corresponding to a "pure" aqueous media (without the presence of surfactants) were obtained by extrapolating the pKa* values determined in in the different methanol - water mixtures (30% - 55% methanol, wt/wt). Protolytic equilibria in the presence of micelles were examined without the use of cosolvent because the surfactants contributed to increasing solubility thereof.The effect of surfactants on protolytic equilibria was estimated based on the shift in the pKaapp values determined in micellar media, in a relation to the pKaw values determined in "pure" water. In the presence of anionic SDS micelles, the pKaapp values of sartans are increased (up to +1.72 pK units), while in the presence of cationic CTAB micelles, the opposite effect was observed and the pKaapp values are decreased (up to -1.44 pK units). On the basis of results in this study, it was assumed that the ionizable centers of the investigated sartans are involved in electrostatic interactions with the surface Stern layer of ionic micelles. The shift in pKaapp values in the presence of nonionic surfactants (-0.86 to +1.30) is a consequence of the interaction of sartans with the hydrophilic, palisade layer of nonionic TX-100 and Brij 35 micelles. The bigest shift in distribution of equilibrium forms of investigated sartans in the presence of micelles (from -44% to + 80%) were observed at a biopharmaceutically significant pH value of 4.5 (corresponding to the pH value in the proximal part of the small intestine) and could be considered in terms of influence on intestinal absorption and bioavailability.Considering the presence of two ionizable centers in the molecule of irbesartan, losartan and valsartan, close values of their ionization constants and overlapped protolytic equilbria, the theoretical study was performed to get better insight in order of their ionization in aqueous media, as well as possible ways of interaction of their equilibrium forms with the micelles...
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Ispitivanje uticaja micela surfaktanata različitog naelektrisanja na protolitičke ravnoteže i rastvorljivost sartana
UR  - https://hdl.handle.net/21.15107/rcub_nardus_17521
ER  - 

@phdthesis{
author = "Grujić, Maja",
year = "2020",
abstract = "Protolitičke ravnoteže sartana (irbesartana, losartana i valsartana) ispitane su bez i u prisustvu surfaktanata različitog naelektrisanja: anjonskog (natrijum-dodecilsulfat ˗ SDS), katjonskog (cetiltrimetilamonijum-bromid ˗ CTAB) i nejonskih (4-oktilfenolpolietoksilat ˗ TX-100 i polioksietilen (23) lauril etar ˗ Brij 35).Sartani su antagonisti angiotenzinskih AT1 receptora koji se koriste u terapiji hipertenzije, srčane insuficijencije i dijabetičke nefropatije. Fizičko-hemijski parametri lekova pKa i rastvorljivost, neophodni za procenu farmakološkog i farmakokinetikog ponašanja, u biosredini mogu imati različite vrednosti u poređenju sa “čisto” vodenom sredinom. Ispitivanjem ovih parametara u uslovima koji su sličniji fiziološkim, stiče se bolji uvid u jonizaciju i rastvorljivost lekova u biosredini. Kao pojednostavljeni simulirajući sistemi za biomembrane u ovom radu su korišćeni rastvori surfaktanata čije micele podražavaju osnovne strukturne i funkcionalne karakteristike biomembrana.U hemijskom pogledu, irbesartan i losartan su amfoliti koji sadrže jedan kiseli centar (tetrazol) i jedan bazni centar (imidazol), dok valsartan sadrži dva kisela centra (tetrazol i karboksilna grupa). Jonizacione konstante su određene potenciometrijski pri konstantnoj jonskoj sili (0,1 M NaCl) i temperaturi 25°C, bez i u prisustvu surfaktanata. Potenciometrijski podaci analizirani su primenom kompjuterskog programa Hyperquad. Zbog male rastvorljivosti sartana u vodi, pKaw vrednosti koje odgovaraju „čisto“vodenoj sredini (bez prisustva surfaktanata) dobijene su ekstrapolacijom praktičnih pKa* vrednosti određenih u smešama metanola i vode, različitog odnosa. Zbog solubilizirajućih efekata surfaktanata, za određivanje jonizacionih konstanti u micelarnoj sredini nisu korišćeni korastvarači.Uticaj surfaktanata na protolitičke ravnoteže procenjen je na osnovu pomeranja pKaapp vrednosti određenih u micelarnoj sredini u odnosu na pKaw vrednosti određenih u „čisto“ vodenoj sredini. U prisustvu anjonskih SDS micela došlo je do porasta pKaapp vrednosti sartana (do +1,72 pK jedinice), dok je u prisustvu katjonskih CTAB micela uočen suprotan efekat i smanjenje pKaapp vrednosti (do -1,44 pK jedinice). Na osnovu rezultata ove studije pretpostavljeno je da su jonizujući centri ispitanih sartana uključeni u elektrostatičke interakcije sa površinskim Sternovim slojem jonskih micela. Pomeranje pKaapp vrednosti pod uticajem nejonskih surfaktanata (od -0,86 do +1,30) posledica je interakcija sartana sa hidrofilnim, palisadnim slojem nejonskih TX-100 i Brij 35 micela. Najveće promene u dijagramima raspodele ravnotežnih oblika ispitanih sartana u prisustvu micela (od -44% do +80%) uočene su na biofarmaceutski značajnoj pH vrednosti 4,5 (odgovara pH vrednosti u proksimalnom delu tankog creva) i mogu se razmatrati u kontekstu potencijalnog uticaja na intestinalnu apsorpciju i bioraspoloživost.Teorijska studija je izvedena sa ciljem da se stekne bolji uvid u preklopljene protolitičke ravnoteže irbesartana, losartana i valsartana, kao i u interakcije njihovih ravnotežnih oblika sa micelama kao simulirajućim sistemima biomembrana. S obzirom na prisustvo dva jonizaciona centra u molekulu ispitivanih sartana i na bliske vrednosti njihovih jonizacionih konstanti, u teorijskoj studiji ispitani su redosled jonizacije irbesartana, losartana i valsartana u vodenoj sredini, kao i mogući načini interakcije njihovih ravnotežnih oblika sa micelama surfaktanata..., Protolytic equilibria of sartans (irbesartan, losartan, and valsartan) were investigated with and without the presence of differently charged surfactants: anionic (sodium dodecyl sulfate ˗ SDS), cationic (cetyltrimethylammonium bromide ˗ CTAB), and nonionic (4-octylphenol polyethoxylate – TX-100 and polyoxyethylene (23) lauryl ether – Brij 35).Sartans are angiotensin AT1 receptor antagonists used in therapy of hypertension, heart failure, and diabetic nephropathy. The most important physicochemical properties of drugs, the pKa values and solubility, necessary for estimation of pharmacological and pharmacokinetic behavior, may have different values in bioenvironment as compared to the "pure" aqueous solution. By examining these parameters under conditions more similar to physiological ones, a better insight in in vivo ionization and solubility of drugs could be achieved. In this work, micellar solutions of surfactants were used as a simplified biomembrane mimetic systems, because of their nature to mimic the most essential structural and functional properties of biomembranes.From the chemical point of view, irbesartan and losartan are ampholytes containing one acidic center (tetrazole) and one basic center (imidazole), whereas valsartan contains two acidic centers (tetrazole and carboxyl group). The ionization constants were determined potentiometrically at a constant ionic strength (0.1 M NaCl) and temperature 25 °C, with and without the presence of surfactants. Potentiometric data were analyzed using the computer program Hyperquad. Due to the poor water solubility of sartans, the pKaw values, corresponding to a "pure" aqueous media (without the presence of surfactants) were obtained by extrapolating the pKa* values determined in in the different methanol - water mixtures (30% - 55% methanol, wt/wt). Protolytic equilibria in the presence of micelles were examined without the use of cosolvent because the surfactants contributed to increasing solubility thereof.The effect of surfactants on protolytic equilibria was estimated based on the shift in the pKaapp values determined in micellar media, in a relation to the pKaw values determined in "pure" water. In the presence of anionic SDS micelles, the pKaapp values of sartans are increased (up to +1.72 pK units), while in the presence of cationic CTAB micelles, the opposite effect was observed and the pKaapp values are decreased (up to -1.44 pK units). On the basis of results in this study, it was assumed that the ionizable centers of the investigated sartans are involved in electrostatic interactions with the surface Stern layer of ionic micelles. The shift in pKaapp values in the presence of nonionic surfactants (-0.86 to +1.30) is a consequence of the interaction of sartans with the hydrophilic, palisade layer of nonionic TX-100 and Brij 35 micelles. The bigest shift in distribution of equilibrium forms of investigated sartans in the presence of micelles (from -44% to + 80%) were observed at a biopharmaceutically significant pH value of 4.5 (corresponding to the pH value in the proximal part of the small intestine) and could be considered in terms of influence on intestinal absorption and bioavailability.Considering the presence of two ionizable centers in the molecule of irbesartan, losartan and valsartan, close values of their ionization constants and overlapped protolytic equilbria, the theoretical study was performed to get better insight in order of their ionization in aqueous media, as well as possible ways of interaction of their equilibrium forms with the micelles...",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Ispitivanje uticaja micela surfaktanata različitog naelektrisanja na protolitičke ravnoteže i rastvorljivost sartana",
url = "https://hdl.handle.net/21.15107/rcub_nardus_17521"
}

Grujić, M.. (2020). Ispitivanje uticaja micela surfaktanata različitog naelektrisanja na protolitičke ravnoteže i rastvorljivost sartana. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_17521

Grujić M. Ispitivanje uticaja micela surfaktanata različitog naelektrisanja na protolitičke ravnoteže i rastvorljivost sartana. in Универзитет у Београду. 2020;.
https://hdl.handle.net/21.15107/rcub_nardus_17521 .

Grujić, Maja, "Ispitivanje uticaja micela surfaktanata različitog naelektrisanja na protolitičke ravnoteže i rastvorljivost sartana" in Универзитет у Београду (2020),
https://hdl.handle.net/21.15107/rcub_nardus_17521 .

TY  - JOUR
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Grujić, Maja
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3167
AB  - The ionization order of sartans in aqueous media and possible way of interactions between their equilibrium forms and surfactant micelles have been theoretically investigated. The examined sartans are ampholytes (irbesartan and losartan) and a diacid (valsartan) with the close values of ionization constants. In order to get a better insight in the overlapped protolytic equilibria of sartans and to predict an affinity of the equilibrium forms interacting with micelles as biomembrane mimetic systems, the theoretical study was performed. Energy calculation of the optimized structures of the equilibrium forms was performed at the B3LYP/6-31G (d,p) level of the Density Functional Theory (DFT). The results of the theoretical study helped to assign the experimentally determined pK(a) values to the corresponding ionizable centers and confirmed that in all examined compounds, the higher pK(a) values can be attributed to ionization of tetrazole. The molecular descriptor values showed that sartans interact predominantly with the micelle surfaces. The equilibrium forms of ampholytes demonstrate higher affinity to the micelles, as compared to the forms of the diprotic acid. Additionally, it was shown that the uncharged molecular forms of ampholytes are more lipophylic then their zwitterionic forms.
PB  - Elsevier Science Inc, New York
T2  - Journal of Molecular Graphics & Modelling
T1  - A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles
VL  - 82
SP  - 67
EP  - 73
DO  - 10.1016/j.jmgm.2018.04.008
ER  - 

@article{
author = "Popović-Nikolić, Marija and Popović, Gordana and Grujić, Maja and Nikolić, Katarina and Agbaba, Danica",
year = "2018",
abstract = "The ionization order of sartans in aqueous media and possible way of interactions between their equilibrium forms and surfactant micelles have been theoretically investigated. The examined sartans are ampholytes (irbesartan and losartan) and a diacid (valsartan) with the close values of ionization constants. In order to get a better insight in the overlapped protolytic equilibria of sartans and to predict an affinity of the equilibrium forms interacting with micelles as biomembrane mimetic systems, the theoretical study was performed. Energy calculation of the optimized structures of the equilibrium forms was performed at the B3LYP/6-31G (d,p) level of the Density Functional Theory (DFT). The results of the theoretical study helped to assign the experimentally determined pK(a) values to the corresponding ionizable centers and confirmed that in all examined compounds, the higher pK(a) values can be attributed to ionization of tetrazole. The molecular descriptor values showed that sartans interact predominantly with the micelle surfaces. The equilibrium forms of ampholytes demonstrate higher affinity to the micelles, as compared to the forms of the diprotic acid. Additionally, it was shown that the uncharged molecular forms of ampholytes are more lipophylic then their zwitterionic forms.",
publisher = "Elsevier Science Inc, New York",
journal = "Journal of Molecular Graphics & Modelling",
title = "A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles",
volume = "82",
pages = "67-73",
doi = "10.1016/j.jmgm.2018.04.008"
}

Popović-Nikolić, M., Popović, G., Grujić, M., Nikolić, K.,& Agbaba, D.. (2018). A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles. in Journal of Molecular Graphics & Modelling
Elsevier Science Inc, New York., 82, 67-73.
https://doi.org/10.1016/j.jmgm.2018.04.008

Popović-Nikolić M, Popović G, Grujić M, Nikolić K, Agbaba D. A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles. in Journal of Molecular Graphics & Modelling. 2018;82:67-73.
doi:10.1016/j.jmgm.2018.04.008 .

Popović-Nikolić, Marija, Popović, Gordana, Grujić, Maja, Nikolić, Katarina, Agbaba, Danica, "A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles" in Journal of Molecular Graphics & Modelling, 82 (2018):67-73,
https://doi.org/10.1016/j.jmgm.2018.04.008 . .

TY  - CONF
AU  - Popović, Marija
AU  - Popović, Gordana
AU  - Nikolić, Katarina
AU  - Grujić, Maja
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5026
AB  - In this study the order of ionization in the molecules of irbesartan, losartan,
and valsartan has been investigated. Irbesartan and losartan are ampholytes,
valsartan is diacid with close values of ionization constants. In order to get
better insight in the overlapped protolytic equilibria of sartans theoretical
study was performed. Energy calculation of the optimized structures of
equilibrium forms was performed at the B3LYP/6-31G (d,p) level of the
Density Functional Theory (DFT). Results of theoretical study
confirmed prediction that in all examined compounds higher pKa values can be
attributed to the ionization of tetrazole.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
T1  - Theoretical study of ionization of sartansin aqueous media
VL  - II
SP  - 801
EP  - 804
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5026
ER  - 

@conference{
author = "Popović, Marija and Popović, Gordana and Nikolić, Katarina and Grujić, Maja and Agbaba, Danica",
year = "2016",
abstract = "In this study the order of ionization in the molecules of irbesartan, losartan,
and valsartan has been investigated. Irbesartan and losartan are ampholytes,
valsartan is diacid with close values of ionization constants. In order to get
better insight in the overlapped protolytic equilibria of sartans theoretical
study was performed. Energy calculation of the optimized structures of
equilibrium forms was performed at the B3LYP/6-31G (d,p) level of the
Density Functional Theory (DFT). Results of theoretical study
confirmed prediction that in all examined compounds higher pKa values can be
attributed to the ionization of tetrazole.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia",
title = "Theoretical study of ionization of sartansin aqueous media",
volume = "II",
pages = "801-804",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5026"
}

Popović, M., Popović, G., Nikolić, K., Grujić, M.,& Agbaba, D.. (2016). Theoretical study of ionization of sartansin aqueous media. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
Society of Physical Chemists of Serbia., II, 801-804.
https://hdl.handle.net/21.15107/rcub_farfar_5026

Popović M, Popović G, Nikolić K, Grujić M, Agbaba D. Theoretical study of ionization of sartansin aqueous media. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia. 2016;II:801-804.
https://hdl.handle.net/21.15107/rcub_farfar_5026 .

Popović, Marija, Popović, Gordana, Nikolić, Katarina, Grujić, Maja, Agbaba, Danica, "Theoretical study of ionization of sartansin aqueous media" in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia, II (2016):801-804,
https://hdl.handle.net/21.15107/rcub_farfar_5026 .

TY  - JOUR
AU  - Grujić, Maja
AU  - Popović, Marija
AU  - Popović, Gordana
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2715
AB  - Protolytic equilibria of irbesartan, losartan, and valsartan have been investigated in the presence and absence of differently charged anionic (sodium dodecyl sulfate), cationic (cetyltrimethylammonium bromide), and nonionic (4-octylphenol polyethoxylate and polyoxyethylene (23) lauryl ether) surfactants. Ionization constants were determined by potentiometric titration at a constant ionic strength (0.1 M NaCl) and temperature 25 degrees C. The effect of surfactants was estimated, based on a shift in apparent ionization constants (pK(a)(app)) determined in micellar solutions against the pK(a)(w) values in water. The anionic surfactant caused an increase in the pK(a)(app) values of sartans (up to 1.72 pK units), while the cationic surfactant had an opposite effect and caused a reduction in pK(a)(app) values (up to -1.44 pK units). These results point out to the fact that the ionizable groups of sartans are involved in electrostatic interactions with the charged surface of the ionic micelles. Shift in the pKa app values in the presence of nonionic surfactants (from -0.86 to +1.30) is a consequence of the interactions of drugs with the hydrophilic palisade layer. Significant changes in the distribution profiles of the equilibrium forms (from -44% to +80%) are observed at the biopharmaceutically important pH 4.5 value and can be considered in terms of the potential influence on intestinal absorption and bioavailability.
PB  - Wiley, Hoboken
T2  - Journal of Pharmaceutical Sciences
T1  - Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants
VL  - 105
IS  - 8
SP  - 2444
EP  - 2452
DO  - 10.1016/j.xphs.2016.06.007
ER  - 

@article{
author = "Grujić, Maja and Popović, Marija and Popović, Gordana and Nikolić, Katarina and Agbaba, Danica",
year = "2016",
abstract = "Protolytic equilibria of irbesartan, losartan, and valsartan have been investigated in the presence and absence of differently charged anionic (sodium dodecyl sulfate), cationic (cetyltrimethylammonium bromide), and nonionic (4-octylphenol polyethoxylate and polyoxyethylene (23) lauryl ether) surfactants. Ionization constants were determined by potentiometric titration at a constant ionic strength (0.1 M NaCl) and temperature 25 degrees C. The effect of surfactants was estimated, based on a shift in apparent ionization constants (pK(a)(app)) determined in micellar solutions against the pK(a)(w) values in water. The anionic surfactant caused an increase in the pK(a)(app) values of sartans (up to 1.72 pK units), while the cationic surfactant had an opposite effect and caused a reduction in pK(a)(app) values (up to -1.44 pK units). These results point out to the fact that the ionizable groups of sartans are involved in electrostatic interactions with the charged surface of the ionic micelles. Shift in the pKa app values in the presence of nonionic surfactants (from -0.86 to +1.30) is a consequence of the interactions of drugs with the hydrophilic palisade layer. Significant changes in the distribution profiles of the equilibrium forms (from -44% to +80%) are observed at the biopharmaceutically important pH 4.5 value and can be considered in terms of the potential influence on intestinal absorption and bioavailability.",
publisher = "Wiley, Hoboken",
journal = "Journal of Pharmaceutical Sciences",
title = "Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants",
volume = "105",
number = "8",
pages = "2444-2452",
doi = "10.1016/j.xphs.2016.06.007"
}

Grujić, M., Popović, M., Popović, G., Nikolić, K.,& Agbaba, D.. (2016). Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants. in Journal of Pharmaceutical Sciences
Wiley, Hoboken., 105(8), 2444-2452.
https://doi.org/10.1016/j.xphs.2016.06.007

Grujić M, Popović M, Popović G, Nikolić K, Agbaba D. Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants. in Journal of Pharmaceutical Sciences. 2016;105(8):2444-2452.
doi:10.1016/j.xphs.2016.06.007 .

Grujić, Maja, Popović, Marija, Popović, Gordana, Nikolić, Katarina, Agbaba, Danica, "Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants" in Journal of Pharmaceutical Sciences, 105, no. 8 (2016):2444-2452,
https://doi.org/10.1016/j.xphs.2016.06.007 . .

TY  - CONF
AU  - Popović, Marija
AU  - Grujić, Maja
AU  - Popović, Gordana
AU  - Agbaba, Danica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5017
AB  - In this study the pKa values of irbesartan, an angiotensin receptor blocker, were
determined by potentiometry and the effects of sodium dodecyl sulfate
(SDS) and cetyl trimethyl ammonium bromide (CTAB) on its protolytic
equilibria have been investigated. It was observed that shift in pKa values is
a result of complex electrostatic and hydrophobic interactions with the
micelar solutions. Based on the obtained results drug interactions with
biomolecules can be evaluated.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia
T1  - The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan
VL  - I
SP  - 1133
EP  - 1136
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5017
ER  - 

@conference{
author = "Popović, Marija and Grujić, Maja and Popović, Gordana and Agbaba, Danica",
year = "2014",
abstract = "In this study the pKa values of irbesartan, an angiotensin receptor blocker, were
determined by potentiometry and the effects of sodium dodecyl sulfate
(SDS) and cetyl trimethyl ammonium bromide (CTAB) on its protolytic
equilibria have been investigated. It was observed that shift in pKa values is
a result of complex electrostatic and hydrophobic interactions with the
micelar solutions. Based on the obtained results drug interactions with
biomolecules can be evaluated.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia",
title = "The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan",
volume = "I",
pages = "1133-1136",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5017"
}

Popović, M., Grujić, M., Popović, G.,& Agbaba, D.. (2014). The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan. in PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia
Society of Physical Chemists of Serbia., I, 1133-1136.
https://hdl.handle.net/21.15107/rcub_farfar_5017

Popović M, Grujić M, Popović G, Agbaba D. The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan. in PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia. 2014;I:1133-1136.
https://hdl.handle.net/21.15107/rcub_farfar_5017 .

Popović, Marija, Grujić, Maja, Popović, Gordana, Agbaba, Danica, "The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan" in PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia, I (2014):1133-1136,
https://hdl.handle.net/21.15107/rcub_farfar_5017 .