TY  - CONF
AU  - Marjanović, Nemanja Ž.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana Ž.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5401
AB  - In the modern drug research the number of practically insoluble potential drugs is increasing. Poor aqueous solubility can cause poor oral absorption and low bioavailability of drugs. Hence, solubility enhancement is considered as one of the most important challenges in the formulation and development of the dosage forms of drugs. Clofazimine (CFZ) is an antibiotic drug which is used in the treatment of tuberculosis and leprosy. It is recently shown that CFZ has inhibitory activity against certain coronaviruses and can antagonize the replication of SARS-CoV-2.1 Since CFZ is highly lipophilic molecule with extremely low solubility, it is quite a challenge to find appropriate method for CFZ solubilization. The aim of this work was to investigate the effect of methanesulfonic (MSA) and glutaric (GA) acids on the solubility of CFZ. The effect of MSA on the solubility of CFZ was studied by the pH-Ramp shake-flask method (pH-RSF).2 The solubility of CFZ was determined in the presence of GA in two ways: 1) by melting a mixture of CFZ and GA in different molar ratios, and then dissolving in water; 2) using the pH-RSF method. Interactions between CZ and GA were investigated by IR spectroscopy. It is shown that both MSA and GA increase the solubility of CFZ in acidic suspensions prepared by pH-RSF method. Also, solubility enhancement was observed in the molten CFZ-GA mixtures (molar ratio 1:1 and 1:4) compared to mixtures prepared without melting. Besides that, the IR spectra of these mixtures revealed that characteristic CFZ band was shifted in molted CFZ-GA mixture (molar ratio 1:1) probably due to CFZ-GA interactions. Preliminary results presented in this study illustrate that MSA and GA can be used for solubility improvement of CFZ.
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  - The effect of methanesulfonic and glutaric acids on the solubility of clofazimine
SP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_cer_5401
ER  - 

@conference{
author = "Marjanović, Nemanja Ž. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana Ž.",
year = "2022",
abstract = "In the modern drug research the number of practically insoluble potential drugs is increasing. Poor aqueous solubility can cause poor oral absorption and low bioavailability of drugs. Hence, solubility enhancement is considered as one of the most important challenges in the formulation and development of the dosage forms of drugs. Clofazimine (CFZ) is an antibiotic drug which is used in the treatment of tuberculosis and leprosy. It is recently shown that CFZ has inhibitory activity against certain coronaviruses and can antagonize the replication of SARS-CoV-2.1 Since CFZ is highly lipophilic molecule with extremely low solubility, it is quite a challenge to find appropriate method for CFZ solubilization. The aim of this work was to investigate the effect of methanesulfonic (MSA) and glutaric (GA) acids on the solubility of CFZ. The effect of MSA on the solubility of CFZ was studied by the pH-Ramp shake-flask method (pH-RSF).2 The solubility of CFZ was determined in the presence of GA in two ways: 1) by melting a mixture of CFZ and GA in different molar ratios, and then dissolving in water; 2) using the pH-RSF method. Interactions between CZ and GA were investigated by IR spectroscopy. It is shown that both MSA and GA increase the solubility of CFZ in acidic suspensions prepared by pH-RSF method. Also, solubility enhancement was observed in the molten CFZ-GA mixtures (molar ratio 1:1 and 1:4) compared to mixtures prepared without melting. Besides that, the IR spectra of these mixtures revealed that characteristic CFZ band was shifted in molted CFZ-GA mixture (molar ratio 1:1) probably due to CFZ-GA interactions. Preliminary results presented in this study illustrate that MSA and GA can be used for solubility improvement of CFZ.",
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 = "The effect of methanesulfonic and glutaric acids on the solubility of clofazimine",
pages = "40",
url = "https://hdl.handle.net/21.15107/rcub_cer_5401"
}

Marjanović, N. Ž., Marković, O. S., Pešić, M. P.,& Verbić, T. Ž.. (2022). The effect of methanesulfonic and glutaric acids on the solubility of clofazimine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
Belgrade : Serbian Chemical Society., 40.
https://hdl.handle.net/21.15107/rcub_cer_5401

Marjanović NŽ, Marković OS, Pešić MP, Verbić TŽ. The effect of methanesulfonic and glutaric acids on the solubility of clofazimine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. 2022;:40.
https://hdl.handle.net/21.15107/rcub_cer_5401 .

Marjanović, Nemanja Ž., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana Ž., "The effect of methanesulfonic and glutaric acids on the solubility of clofazimine" in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 (2022):40,
https://hdl.handle.net/21.15107/rcub_cer_5401 .

TY  - CONF
AU  - Marković, Olivera
AU  - Marjanović, Nemanja Ž.
AU  - Patel, Nirali
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4730
AB  - Solubility is important physicochemical parameter and determines drug stability, bioavailability and 
therapeutic action. The aim of this study was to examine solubility of nortriptyline hydrochloride in 
a wide pH range, using pH-Ramp Shake-Flask method, already applied to desipramine 
hydrochloride [1] and based of recently published recommendations [2]. Solubility was measured in phosphate buffer, in chloride-free media and phoshate-free media, using both nortriptyline base and nortriptyline hydrochloride as starting material. Elemental analysis, termogravimetric analysis, 
differential scaning calorimetric analysis and powder X-ray diffraction analysis were used for solid 
precipitate analysis.
AB  - Rastvorljivost je značajno fizičko-hemijsko svojstvo biološki aktivnih i potencijalno biološki 
aktivnih supstancija, koje određuje stabilnost, biodostupnost i terapeutsko dejstvo leka. Cilj ovog 
rada je ispitivanje rastvorljivosti nortriptilin-hidrohlorida, pomoću pH-Ramp Shake-Flask metode, 
prethodno primenjene na desipramin-hidrohlorid [1]. Eksperimenti su izvedeni prema novim 
preporukama iz literature [2]. Rastvorljivost je određena u fosfatnom puferu, u sistemu bez hlorida i 
sistemu bez fosfata, koristeći nortriptilin bazu i nortriptilin-hidrohlorid. Urađena je i katakterizacija
čvrste faze pomoću elementalne analize, termogravimetrije, diferencijalne skenirajuće kalorimetrije 
i difrakcije X-zraka.
PB  - Belgrade : Serbian Chemical Society
C3  - Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva
T1  - pH-Dependent solubility profile of nortriptyline hydrochloride
SP  - 32
EP  - 32
UR  - https://hdl.handle.net/21.15107/rcub_cer_4730
ER  - 

@conference{
author = "Marković, Olivera and Marjanović, Nemanja Ž. and Patel, Nirali and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2021",
abstract = "Solubility is important physicochemical parameter and determines drug stability, bioavailability and 
therapeutic action. The aim of this study was to examine solubility of nortriptyline hydrochloride in 
a wide pH range, using pH-Ramp Shake-Flask method, already applied to desipramine 
hydrochloride [1] and based of recently published recommendations [2]. Solubility was measured in phosphate buffer, in chloride-free media and phoshate-free media, using both nortriptyline base and nortriptyline hydrochloride as starting material. Elemental analysis, termogravimetric analysis, 
differential scaning calorimetric analysis and powder X-ray diffraction analysis were used for solid 
precipitate analysis., Rastvorljivost je značajno fizičko-hemijsko svojstvo biološki aktivnih i potencijalno biološki 
aktivnih supstancija, koje određuje stabilnost, biodostupnost i terapeutsko dejstvo leka. Cilj ovog 
rada je ispitivanje rastvorljivosti nortriptilin-hidrohlorida, pomoću pH-Ramp Shake-Flask metode, 
prethodno primenjene na desipramin-hidrohlorid [1]. Eksperimenti su izvedeni prema novim 
preporukama iz literature [2]. Rastvorljivost je određena u fosfatnom puferu, u sistemu bez hlorida i 
sistemu bez fosfata, koristeći nortriptilin bazu i nortriptilin-hidrohlorid. Urađena je i katakterizacija
čvrste faze pomoću elementalne analize, termogravimetrije, diferencijalne skenirajuće kalorimetrije 
i difrakcije X-zraka.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva",
title = "pH-Dependent solubility profile of nortriptyline hydrochloride",
pages = "32-32",
url = "https://hdl.handle.net/21.15107/rcub_cer_4730"
}

Marković, O., Marjanović, N. Ž., Patel, N., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2021). pH-Dependent solubility profile of nortriptyline hydrochloride. in Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva
Belgrade : Serbian Chemical Society., 32-32.
https://hdl.handle.net/21.15107/rcub_cer_4730

Marković O, Marjanović NŽ, Patel N, Serajuddin ATM, Avdeef A, Verbić T. pH-Dependent solubility profile of nortriptyline hydrochloride. in Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva. 2021;:32-32.
https://hdl.handle.net/21.15107/rcub_cer_4730 .

Marković, Olivera, Marjanović, Nemanja Ž., Patel, Nirali, Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "pH-Dependent solubility profile of nortriptyline hydrochloride" in Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva (2021):32-32,
https://hdl.handle.net/21.15107/rcub_cer_4730 .