TY  - CONF
AU  - Marjanović, Nemanja Ž.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5938
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  - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
T1  - The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine
SP  - 40
EP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5938
ER  - 

@conference{
author = "Marjanović, Nemanja Ž. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana",
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 = "8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts",
title = "The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine",
pages = "40-40",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5938"
}

Marjanović, N. Ž., Marković, O. S., Pešić, M. P.,& Verbić, T.. (2022). The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts
Belgrade : Serbian Chemical Society., 40-40.
https://hdl.handle.net/21.15107/rcub_cherry_5938

Marjanović NŽ, Marković OS, Pešić MP, Verbić T. The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine. in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts. 2022;:40-40.
https://hdl.handle.net/21.15107/rcub_cherry_5938 .

Marjanović, Nemanja Ž., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana, "The effect  of methanesulfonic and glutaric acids on the solubility of clofazimine" in 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. In: Book of Abstracts (2022):40-40,
https://hdl.handle.net/21.15107/rcub_cherry_5938 .

TY  - THES
AU  - Marjanović, Nemanja Ž.
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5601
AB  - Rastvorljivost se definiše kao maksimalna koncentracija rastvorene supstance u nekom
rastvaraču na određenoj temperaturi. Rastvorljivost predstavlja važan fizičko-hemijski
parameter koji utiče na biodostupnost biološki aktivnih jedinjenja. Povećanje
rastvorljivosti i biodostupnosti biološki aktivnih jedinjenja je najvažniji aspekt u dizajnu
i razvoju lekova.
Klofazimin je derivat iminofenazina i koristi se u lečenju lepre i tuberkuloze. Cilj ovog
završnog rada bio je ispitivanje uticaja glutarne i metansulfonske kiseline na
rastvorljivost klofazimina, teško rastvornog leka. Rastvorljivost klofazimina određena je
u prisustvu glutarne kiseline na dva načina: Rastvorljivost klofazimina određena je u
prisustvu glutarne kiseline na dva načina: 1) topljenjem smeša klofazimina i glutarne
kiseline u različitim molskim odnosima, a zatim naknadnim rastvaranjem u vodi i 2)
primenom pH-Ramp shake-flask metode. Ispitivanje uticaja metansulfonske kiseline na
rastvorljivost klofazimina izvođena je primenom pH-Ramp shake-flask metode.
Primećeno je da rastopi klofazimina i glutarne kiseline imaju veću rastvorljivost od
čvrstih smeša koje nisu topljene, što dovodi do povećanja rastvorljivosti. Primećena je i
veća rastvorljivost klofazimina u prisustvu glutarne kiseline u odnosu na prisustvo
metansulfonske kiseline.
T1  - Ispitivanje uticaja glutarne i metansulfonske kiseline na rastvorljivost klofazimina
SP  - 1
EP  - 60
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5601
ER  - 

@mastersthesis{
author = "Marjanović, Nemanja Ž.",
year = "2022",
abstract = "Rastvorljivost se definiše kao maksimalna koncentracija rastvorene supstance u nekom
rastvaraču na određenoj temperaturi. Rastvorljivost predstavlja važan fizičko-hemijski
parameter koji utiče na biodostupnost biološki aktivnih jedinjenja. Povećanje
rastvorljivosti i biodostupnosti biološki aktivnih jedinjenja je najvažniji aspekt u dizajnu
i razvoju lekova.
Klofazimin je derivat iminofenazina i koristi se u lečenju lepre i tuberkuloze. Cilj ovog
završnog rada bio je ispitivanje uticaja glutarne i metansulfonske kiseline na
rastvorljivost klofazimina, teško rastvornog leka. Rastvorljivost klofazimina određena je
u prisustvu glutarne kiseline na dva načina: Rastvorljivost klofazimina određena je u
prisustvu glutarne kiseline na dva načina: 1) topljenjem smeša klofazimina i glutarne
kiseline u različitim molskim odnosima, a zatim naknadnim rastvaranjem u vodi i 2)
primenom pH-Ramp shake-flask metode. Ispitivanje uticaja metansulfonske kiseline na
rastvorljivost klofazimina izvođena je primenom pH-Ramp shake-flask metode.
Primećeno je da rastopi klofazimina i glutarne kiseline imaju veću rastvorljivost od
čvrstih smeša koje nisu topljene, što dovodi do povećanja rastvorljivosti. Primećena je i
veća rastvorljivost klofazimina u prisustvu glutarne kiseline u odnosu na prisustvo
metansulfonske kiseline.",
title = "Ispitivanje uticaja glutarne i metansulfonske kiseline na rastvorljivost klofazimina",
pages = "1-60",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5601"
}

Marjanović, N. Ž.. (2022). Ispitivanje uticaja glutarne i metansulfonske kiseline na rastvorljivost klofazimina. , 1-60.
https://hdl.handle.net/21.15107/rcub_cherry_5601

Marjanović NŽ. Ispitivanje uticaja glutarne i metansulfonske kiseline na rastvorljivost klofazimina. 2022;:1-60.
https://hdl.handle.net/21.15107/rcub_cherry_5601 .

Marjanović, Nemanja Ž., "Ispitivanje uticaja glutarne i metansulfonske kiseline na rastvorljivost klofazimina" (2022):1-60,
https://hdl.handle.net/21.15107/rcub_cherry_5601 .

TY  - CONF
AU  - Marković, Olivera S.
AU  - Marjanović, Nemanja Ž.
AU  - Patel, Nirali
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2021
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5962
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  - 57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021
T1  - pH-Dependent solubility profile of nortriptyline hydrochloride
SP  - 32
EP  - 32
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5962
ER  - 

@conference{
author = "Marković, Olivera S. 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 = "57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021",
title = "pH-Dependent solubility profile of nortriptyline hydrochloride",
pages = "32-32",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5962"
}

Marković, O. S., Marjanović, N. Ž., Patel, N., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2021). pH-Dependent solubility profile of nortriptyline hydrochloride. in 57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021
Belgrade : Serbian Chemical Society., 32-32.
https://hdl.handle.net/21.15107/rcub_cherry_5962

Marković OS, Marjanović NŽ, Patel N, Serajuddin ATM, Avdeef A, Verbić T. pH-Dependent solubility profile of nortriptyline hydrochloride. in 57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021. 2021;:32-32.
https://hdl.handle.net/21.15107/rcub_cherry_5962 .

Marković, Olivera S., Marjanović, Nemanja Ž., Patel, Nirali, Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "pH-Dependent solubility profile of nortriptyline hydrochloride" in 57th Meeting of the Serbian chemical Society - Proceedings / 57. Savetovanje Srpskog hemijskog društva - Knjiga radova, Kragujevac, Serbia, June 18-19, 2021 (2021):32-32,
https://hdl.handle.net/21.15107/rcub_cherry_5962 .

TY  - THES
AU  - Marjanović, Nemanja Ž.
PY  - 2021
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/4572
AB  - Rastvorljivost se izražava kao koncentracija supstance u određenoj zapremini rastvarača na određenoj temperaturi i predstavlja važan fizičko-hemijski parametar u ranoj fazi dizajna i razvoja lekova. Nortriptilin-hidrohlorid spada u grupu tricikličnih antidepresiva koji se koriste u lečenju depresije. pH-Zavisna rastvorljivost nortriptilin-hidrohlorida proučavana je primenom pH-Ramp shake-flask metode. Određivanje rastvorljivosti je od velikog značaja, budući da je u digestivnom traktu zastupljen širok opseg pH vrednosti (od jako kisele sredine u želucu do slabo bazne u crevima), pa samim tim visoka rastvorljivost jonizovanog (kiselog ili baznog) oblika supstance omogućava bolju apsorpciju iz digestivnog trakta u krvotok i veću biodostupnost na mestu dejstva. Primenom softverskog paketa pDISOL-X (in-ADME Research, New York, USA) određene su ravnoteže u heterogenom sistemu koji čini nortriptilin-hidrohlorid i fosfatni pufer.
T1  - Proučavanje pH-zavisne rastvorljivosti nortriptilin-hidrohlorida primenom pH-Ramp shake-flask metode
SP  - 1
EP  - 50
UR  - https://hdl.handle.net/21.15107/rcub_cherry_4572
ER  - 

@misc{
author = "Marjanović, Nemanja Ž.",
year = "2021",
abstract = "Rastvorljivost se izražava kao koncentracija supstance u određenoj zapremini rastvarača na određenoj temperaturi i predstavlja važan fizičko-hemijski parametar u ranoj fazi dizajna i razvoja lekova. Nortriptilin-hidrohlorid spada u grupu tricikličnih antidepresiva koji se koriste u lečenju depresije. pH-Zavisna rastvorljivost nortriptilin-hidrohlorida proučavana je primenom pH-Ramp shake-flask metode. Određivanje rastvorljivosti je od velikog značaja, budući da je u digestivnom traktu zastupljen širok opseg pH vrednosti (od jako kisele sredine u želucu do slabo bazne u crevima), pa samim tim visoka rastvorljivost jonizovanog (kiselog ili baznog) oblika supstance omogućava bolju apsorpciju iz digestivnog trakta u krvotok i veću biodostupnost na mestu dejstva. Primenom softverskog paketa pDISOL-X (in-ADME Research, New York, USA) određene su ravnoteže u heterogenom sistemu koji čini nortriptilin-hidrohlorid i fosfatni pufer.",
title = "Proučavanje pH-zavisne rastvorljivosti nortriptilin-hidrohlorida primenom pH-Ramp shake-flask metode",
pages = "1-50",
url = "https://hdl.handle.net/21.15107/rcub_cherry_4572"
}

Marjanović, N. Ž.. (2021). Proučavanje pH-zavisne rastvorljivosti nortriptilin-hidrohlorida primenom pH-Ramp shake-flask metode. , 1-50.
https://hdl.handle.net/21.15107/rcub_cherry_4572

Marjanović NŽ. Proučavanje pH-zavisne rastvorljivosti nortriptilin-hidrohlorida primenom pH-Ramp shake-flask metode. 2021;:1-50.
https://hdl.handle.net/21.15107/rcub_cherry_4572 .

Marjanović, Nemanja Ž., "Proučavanje pH-zavisne rastvorljivosti nortriptilin-hidrohlorida primenom pH-Ramp shake-flask metode" (2021):1-50,
https://hdl.handle.net/21.15107/rcub_cherry_4572 .