Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride
Само за регистроване кориснике
2024
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The acid–base equilibria of raloxifene and the mutual influence of pH and solubility enhancers on the solubility of raloxifene
hydrochloride were studied. The apparent ionization constants (pKa*) of raloxifene were determined potentiometrically in
methanol–water mixtures (45%-55% w/w), and the pKa values (pKa1 = 7.21 ± 0.02, pKa2 = 7.86 ± 0.02, pKa3 = 9.97 ± 0.04)
defining ionization in aqueous media were obtained by extrapolating the pKa* values to 0% of methanol. The obtained pKa
values were assigned to the corresponding ionization centers. Based on the ionization constants obtained in this study, the
distribution of the equilibrium forms of raloxifene was calculated. The solubility of raloxifene hydrochloride in 0.01 M
HCl, acetate buffer pH 4.5 and phosphate buffer pH 6.8 was studied with and without the presence of β-CD, HP-β-CD and
polysorbate 80. The most effective solubility enhancer of raloxifene hydrochloride in 0.01 M HCl was polysorbate 80 at a
concentration of 0.5%..., while the influence of this enhancer in phosphate buffer pH 6.8 was negligible. The highest solubility
of raloxifene hydrochloride in acetate and phosphate buffer was achieved in the presence of 10–
3 M HP–β-CD which
was 1.3-fold higher in both 0.01 M HCl and acetate buffer and 2.3-fold higher in phosphate buffer than in the presence of
10–
3 M β-CD.
Кључне речи:
Physicochemical properties / Solubility / Equilibria / Biopharmaceutics classification system (BCS) / Cyclodextrins / BioavailabilityИзвор:
Chemical Papers, 2024Издавач:
- Springer Nature
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
- European Cooperation in Science and Technology (COST) COST Actions CA18240 and CA18133
Институција/група
PharmacyTY - JOUR AU - Popović-Nikolić, Marija AU - Čakar, Mira AU - Todorović, Nina AU - Nikolić, Katarina AU - Popović, Gordana PY - 2024 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5589 AB - The acid–base equilibria of raloxifene and the mutual influence of pH and solubility enhancers on the solubility of raloxifene hydrochloride were studied. The apparent ionization constants (pKa*) of raloxifene were determined potentiometrically in methanol–water mixtures (45%-55% w/w), and the pKa values (pKa1 = 7.21 ± 0.02, pKa2 = 7.86 ± 0.02, pKa3 = 9.97 ± 0.04) defining ionization in aqueous media were obtained by extrapolating the pKa* values to 0% of methanol. The obtained pKa values were assigned to the corresponding ionization centers. Based on the ionization constants obtained in this study, the distribution of the equilibrium forms of raloxifene was calculated. The solubility of raloxifene hydrochloride in 0.01 M HCl, acetate buffer pH 4.5 and phosphate buffer pH 6.8 was studied with and without the presence of β-CD, HP-β-CD and polysorbate 80. The most effective solubility enhancer of raloxifene hydrochloride in 0.01 M HCl was polysorbate 80 at a concentration of 0.5%, while the influence of this enhancer in phosphate buffer pH 6.8 was negligible. The highest solubility of raloxifene hydrochloride in acetate and phosphate buffer was achieved in the presence of 10– 3 M HP–β-CD which was 1.3-fold higher in both 0.01 M HCl and acetate buffer and 2.3-fold higher in phosphate buffer than in the presence of 10– 3 M β-CD. PB - Springer Nature T2 - Chemical Papers T1 - Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride DO - 10.1007/s11696-024-03399-1 ER -
@article{ author = "Popović-Nikolić, Marija and Čakar, Mira and Todorović, Nina and Nikolić, Katarina and Popović, Gordana", year = "2024", abstract = "The acid–base equilibria of raloxifene and the mutual influence of pH and solubility enhancers on the solubility of raloxifene hydrochloride were studied. The apparent ionization constants (pKa*) of raloxifene were determined potentiometrically in methanol–water mixtures (45%-55% w/w), and the pKa values (pKa1 = 7.21 ± 0.02, pKa2 = 7.86 ± 0.02, pKa3 = 9.97 ± 0.04) defining ionization in aqueous media were obtained by extrapolating the pKa* values to 0% of methanol. The obtained pKa values were assigned to the corresponding ionization centers. Based on the ionization constants obtained in this study, the distribution of the equilibrium forms of raloxifene was calculated. The solubility of raloxifene hydrochloride in 0.01 M HCl, acetate buffer pH 4.5 and phosphate buffer pH 6.8 was studied with and without the presence of β-CD, HP-β-CD and polysorbate 80. The most effective solubility enhancer of raloxifene hydrochloride in 0.01 M HCl was polysorbate 80 at a concentration of 0.5%, while the influence of this enhancer in phosphate buffer pH 6.8 was negligible. The highest solubility of raloxifene hydrochloride in acetate and phosphate buffer was achieved in the presence of 10– 3 M HP–β-CD which was 1.3-fold higher in both 0.01 M HCl and acetate buffer and 2.3-fold higher in phosphate buffer than in the presence of 10– 3 M β-CD.", publisher = "Springer Nature", journal = "Chemical Papers", title = "Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride", doi = "10.1007/s11696-024-03399-1" }
Popović-Nikolić, M., Čakar, M., Todorović, N., Nikolić, K.,& Popović, G.. (2024). Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride. in Chemical Papers Springer Nature.. https://doi.org/10.1007/s11696-024-03399-1
Popović-Nikolić M, Čakar M, Todorović N, Nikolić K, Popović G. Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride. in Chemical Papers. 2024;. doi:10.1007/s11696-024-03399-1 .
Popović-Nikolić, Marija, Čakar, Mira, Todorović, Nina, Nikolić, Katarina, Popović, Gordana, "Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride" in Chemical Papers (2024), https://doi.org/10.1007/s11696-024-03399-1 . .