Investigation of clofazimine acid-base supersolubilization using various weak organic acids
Апстракт
Nowadays, more than two-thirds of potential drugs currently being discovered are practically insoluble in water with solubility <100 μg/mL. Despite that, compounds with even lower solubility (<0.1 μg/mL) are commonly selected for further development which is very challenging, especially in the pharmaceutical formulation process1. Clofazimine (CFZ), an anti-leprosy drug with inhibitory activity against several coronaviruses, has a favourable safety profile2, but it is poorly soluble in aqueous media. Hence, it is important to develop a method for increasing its solubility. In this work, a relatively novel approach of enhancing solubility of weakly basic drugs by using weak acids that would not form salts with the drug (acid-base supersolubilization (ABS)) has been applied. CFZ aqueous solubility was determined in solutions of tartaric, citric, malic, malonic or maleic acid: in set I acid solutions had the same concentration (2.5 mol/L), and in the set II they were scaled to the same pH ...(1.0). The drug was added in stirred acid solution until a precipitate was noticed and, after filtration, CFZ concentration in samples was determined by HPLC. Based on set I, it was found that the solubility of CFZ had the highest value in the case of tartaric acid (0.46 mg/mL) compared to other acid solutions of the same concentration. In set II the highest CFZ concentration was determined in the malic acid solution which had the highest concentration (2.8 mol/L) among other acids. On contrary, maleic acid solution at pH=1.0 had the lowest molar concentration (0.5 mol/L) and therefore CFZ was minimally dissolved. Further research will be directed toward the examination of acid structure effect on CFZ solubility.
Кључне речи:
solubility / ClofazimineИзвор:
Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022, 2022, 37-Издавач:
- Belgrade : Serbian Chemical Society
- Belgrade : Serbian Young Chemists’ Club
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200026 (Универзитет у Београду, Институт за хемију, технологију и металургију - ИХТМ) (RS-MESTD-inst-2020-200026)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200168 (Универзитет у Београду, Хемијски факултет) (RS-MESTD-inst-2020-200168)
Институција/група
IHTMTY - CONF AU - Topalović, Igor A. AU - Marković, Olivera S. AU - Pešić, Miloš P. AU - Verbić, Tatjana Ž. PY - 2022 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/5397 AB - Nowadays, more than two-thirds of potential drugs currently being discovered are practically insoluble in water with solubility <100 μg/mL. Despite that, compounds with even lower solubility (<0.1 μg/mL) are commonly selected for further development which is very challenging, especially in the pharmaceutical formulation process1. Clofazimine (CFZ), an anti-leprosy drug with inhibitory activity against several coronaviruses, has a favourable safety profile2, but it is poorly soluble in aqueous media. Hence, it is important to develop a method for increasing its solubility. In this work, a relatively novel approach of enhancing solubility of weakly basic drugs by using weak acids that would not form salts with the drug (acid-base supersolubilization (ABS)) has been applied. CFZ aqueous solubility was determined in solutions of tartaric, citric, malic, malonic or maleic acid: in set I acid solutions had the same concentration (2.5 mol/L), and in the set II they were scaled to the same pH (1.0). The drug was added in stirred acid solution until a precipitate was noticed and, after filtration, CFZ concentration in samples was determined by HPLC. Based on set I, it was found that the solubility of CFZ had the highest value in the case of tartaric acid (0.46 mg/mL) compared to other acid solutions of the same concentration. In set II the highest CFZ concentration was determined in the malic acid solution which had the highest concentration (2.8 mol/L) among other acids. On contrary, maleic acid solution at pH=1.0 had the lowest molar concentration (0.5 mol/L) and therefore CFZ was minimally dissolved. Further research will be directed toward the examination of acid structure effect on CFZ solubility. PB - Belgrade : Serbian Chemical Society PB - Belgrade : Serbian Young Chemists’ Club C3 - Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 T1 - Investigation of clofazimine acid-base supersolubilization using various weak organic acids SP - 37 UR - https://hdl.handle.net/21.15107/rcub_cer_5397 ER -
@conference{ author = "Topalović, Igor A. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana Ž.", year = "2022", abstract = "Nowadays, more than two-thirds of potential drugs currently being discovered are practically insoluble in water with solubility <100 μg/mL. Despite that, compounds with even lower solubility (<0.1 μg/mL) are commonly selected for further development which is very challenging, especially in the pharmaceutical formulation process1. Clofazimine (CFZ), an anti-leprosy drug with inhibitory activity against several coronaviruses, has a favourable safety profile2, but it is poorly soluble in aqueous media. Hence, it is important to develop a method for increasing its solubility. In this work, a relatively novel approach of enhancing solubility of weakly basic drugs by using weak acids that would not form salts with the drug (acid-base supersolubilization (ABS)) has been applied. CFZ aqueous solubility was determined in solutions of tartaric, citric, malic, malonic or maleic acid: in set I acid solutions had the same concentration (2.5 mol/L), and in the set II they were scaled to the same pH (1.0). The drug was added in stirred acid solution until a precipitate was noticed and, after filtration, CFZ concentration in samples was determined by HPLC. Based on set I, it was found that the solubility of CFZ had the highest value in the case of tartaric acid (0.46 mg/mL) compared to other acid solutions of the same concentration. In set II the highest CFZ concentration was determined in the malic acid solution which had the highest concentration (2.8 mol/L) among other acids. On contrary, maleic acid solution at pH=1.0 had the lowest molar concentration (0.5 mol/L) and therefore CFZ was minimally dissolved. Further research will be directed toward the examination of acid structure effect on CFZ solubility.", publisher = "Belgrade : Serbian Chemical Society, Belgrade : Serbian Young Chemists’ Club", journal = "Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022", title = "Investigation of clofazimine acid-base supersolubilization using various weak organic acids", pages = "37", url = "https://hdl.handle.net/21.15107/rcub_cer_5397" }
Topalović, I. A., Marković, O. S., Pešić, M. P.,& Verbić, T. Ž.. (2022). Investigation of clofazimine acid-base supersolubilization using various weak organic acids. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 Belgrade : Serbian Chemical Society., 37. https://hdl.handle.net/21.15107/rcub_cer_5397
Topalović IA, Marković OS, Pešić MP, Verbić TŽ. Investigation of clofazimine acid-base supersolubilization using various weak organic acids. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. 2022;:37. https://hdl.handle.net/21.15107/rcub_cer_5397 .
Topalović, Igor A., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana Ž., "Investigation of clofazimine acid-base supersolubilization using various weak organic acids" in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 (2022):37, https://hdl.handle.net/21.15107/rcub_cer_5397 .