Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Montelukast is a leukotriene receptor antagonist indicated for asthma prophylaxis in adults
as well as in pediatric patients 6 months of age and older. Because it is associated with
numerous side effects, including neuropsychiatric events, it is very important to monitor its
pharmacologic behavior when administered chronically. To gain better insight into the
pharmacological properties of ionizable drugs, their physicochemical properties should be
studied under conditions more similar to physiological, such as micellar solutions of
surfactants as biomembrane mimetic systems. Montelukast is an ampholyte with one acidic
(carboxyl) and one basic (quinoline nitrogen) group. In this study the effects of micellar
solutions of differently charged surfactants (anionic SDS, cationic CTAB, and nonionic TX-
100) on protolytic equilibria of montelukast were investigated potentiometrically. Solutions were titrated with standard NaOH solution (0.1017 M) at a constant ionic strength (0.1 M N...aCl) and a temperature 25°C. Experimental data were analyzed using the Hyperquad program. Due to poor water solubility, the pKa values defining the ionization in water (pKa1 =4.07, pKa2 = 5.49), were obtained indirectly by extrapolation from the pKa* values determined potentiometrically in the different methanol-water mixtures (40%, 50%, and 55% wt/wt). The pKa values in 0.01M micellar solutions were determined without the use of cosolvent. Micelles contributed to the shift in protolytic equilibria of montelukast, anionic ΔpKa up to +1.20, cationic ΔpKa up to +0.27, and nonionic ΔpKa up to +0.98. More pronounced effects are observed on the ionization of carboxyl group than quinoline nitrogen. A change in the distribution of equilibrium forms in a relation to pure water, can be expected in physiological conditions, in interactions of montelukast with polar or charged biomolecules.
Кључне речи:
leukotriene receptor antagonist / micelles / biomembrane mimetic systems / protolytic equilibria / hyperquadИзвор:
10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6, 2023, 49-49Издавач:
- International Association of Physical Chemists
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
- COST Actions CA18240 and CA18133
Напомена:
- 10th IAPC Meeting, Book of Abstracts
Институција/група
PharmacyTY - CONF AU - Popović-Nikolić, Marija AU - Oljačić, Slavica AU - Nikolić, Katarina AU - Popović, Gordana PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5004 AB - Montelukast is a leukotriene receptor antagonist indicated for asthma prophylaxis in adults as well as in pediatric patients 6 months of age and older. Because it is associated with numerous side effects, including neuropsychiatric events, it is very important to monitor its pharmacologic behavior when administered chronically. To gain better insight into the pharmacological properties of ionizable drugs, their physicochemical properties should be studied under conditions more similar to physiological, such as micellar solutions of surfactants as biomembrane mimetic systems. Montelukast is an ampholyte with one acidic (carboxyl) and one basic (quinoline nitrogen) group. In this study the effects of micellar solutions of differently charged surfactants (anionic SDS, cationic CTAB, and nonionic TX- 100) on protolytic equilibria of montelukast were investigated potentiometrically. Solutions were titrated with standard NaOH solution (0.1017 M) at a constant ionic strength (0.1 M NaCl) and a temperature 25°C. Experimental data were analyzed using the Hyperquad program. Due to poor water solubility, the pKa values defining the ionization in water (pKa1 =4.07, pKa2 = 5.49), were obtained indirectly by extrapolation from the pKa* values determined potentiometrically in the different methanol-water mixtures (40%, 50%, and 55% wt/wt). The pKa values in 0.01M micellar solutions were determined without the use of cosolvent. Micelles contributed to the shift in protolytic equilibria of montelukast, anionic ΔpKa up to +1.20, cationic ΔpKa up to +0.27, and nonionic ΔpKa up to +0.98. More pronounced effects are observed on the ionization of carboxyl group than quinoline nitrogen. A change in the distribution of equilibrium forms in a relation to pure water, can be expected in physiological conditions, in interactions of montelukast with polar or charged biomolecules. PB - International Association of Physical Chemists C3 - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 T1 - Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems SP - 49 EP - 49 UR - https://hdl.handle.net/21.15107/rcub_farfar_5004 ER -
@conference{ author = "Popović-Nikolić, Marija and Oljačić, Slavica and Nikolić, Katarina and Popović, Gordana", year = "2023", abstract = "Montelukast is a leukotriene receptor antagonist indicated for asthma prophylaxis in adults as well as in pediatric patients 6 months of age and older. Because it is associated with numerous side effects, including neuropsychiatric events, it is very important to monitor its pharmacologic behavior when administered chronically. To gain better insight into the pharmacological properties of ionizable drugs, their physicochemical properties should be studied under conditions more similar to physiological, such as micellar solutions of surfactants as biomembrane mimetic systems. Montelukast is an ampholyte with one acidic (carboxyl) and one basic (quinoline nitrogen) group. In this study the effects of micellar solutions of differently charged surfactants (anionic SDS, cationic CTAB, and nonionic TX- 100) on protolytic equilibria of montelukast were investigated potentiometrically. Solutions were titrated with standard NaOH solution (0.1017 M) at a constant ionic strength (0.1 M NaCl) and a temperature 25°C. Experimental data were analyzed using the Hyperquad program. Due to poor water solubility, the pKa values defining the ionization in water (pKa1 =4.07, pKa2 = 5.49), were obtained indirectly by extrapolation from the pKa* values determined potentiometrically in the different methanol-water mixtures (40%, 50%, and 55% wt/wt). The pKa values in 0.01M micellar solutions were determined without the use of cosolvent. Micelles contributed to the shift in protolytic equilibria of montelukast, anionic ΔpKa up to +1.20, cationic ΔpKa up to +0.27, and nonionic ΔpKa up to +0.98. More pronounced effects are observed on the ionization of carboxyl group than quinoline nitrogen. A change in the distribution of equilibrium forms in a relation to pure water, can be expected in physiological conditions, in interactions of montelukast with polar or charged biomolecules.", publisher = "International Association of Physical Chemists", journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6", title = "Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems", pages = "49-49", url = "https://hdl.handle.net/21.15107/rcub_farfar_5004" }
Popović-Nikolić, M., Oljačić, S., Nikolić, K.,& Popović, G.. (2023). Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 International Association of Physical Chemists., 49-49. https://hdl.handle.net/21.15107/rcub_farfar_5004
Popović-Nikolić M, Oljačić S, Nikolić K, Popović G. Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:49-49. https://hdl.handle.net/21.15107/rcub_farfar_5004 .
Popović-Nikolić, Marija, Oljačić, Slavica, Nikolić, Katarina, Popović, Gordana, "Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):49-49, https://hdl.handle.net/21.15107/rcub_farfar_5004 .