TY  - CONF
AU  - Marković, Olivera
AU  - Mrđinac, Jelena Ž.
AU  - Pepić, Sara
AU  - Verbić, Tatjana
PY  - 2024
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7656
AB  - The solubility profile of a drug typically consists of two independent curves that intersect 
at a specific point called pHmax. At pHmax, both salt and base coexist as solid phases. While 
two solids coexist, pH and solubility in the heterogeneous system remain constant 
(according to the Gibbs Phase Rule). Recent studies, however, have shown that pH and 
solubility might change during the salt-to-free-base transformation. This pH range, 
containing two solids, is termed the pHmax – pHmin range. pHmax refers to the pH value at 
the maximum solubility of a eutectic mixture, whereas pHmin represents the pH value at the 
minimum solubility of the eutectic mixture. The objective of this study was to investigate 
the influence of suspension concentration (the ratio of drug mass to suspension volume) on 
the pHmax – pHmin range during solubility determination using the pH-Ramp shake-flask
method. Nortriptyline hydrochloride (Nor, monoprotic base) and atorvastatin calcium (At, 
monoprotic acid) were employed as model compounds. Results indicate that the pHmax –
pHmin range increases as suspension concentration rises (for 20.10 mg NorHCl/mL: 
pHmax=3.55, ΔpH=0; for 59.82 mg NorHCl/mL: pHmax – pHmin= 3.56 – 4.52, ΔpH=0.96). 
Understanding the details of the pHmax – pHmin range could significantly impact product 
formulation optimization in drug research.
AB  - Cilj ovog rada bio je ispitivanje uticaja koncentracije suspenzije na širinu pHmax – pHmin
opsega tokom određivanja rastvorljivosti pH-Ramp shake-flask metodom. Kao model 
jedinjenja izabrani su nortriptilin-hidrohlorid i atorvastatin-kalcijum. Rezultati su pokazali 
da sa porastom koncentracije suspenzije dolazi do širenja opsega pHmax – pHmin, a ovakva 
proučavanja mogu značajno doprineti optimizaciji formulacije u procesu dizajna i razvoja 
lekova.
PB  - Serbian Chemical Society
C3  - 60th Meeting of the Serbian Chemical Society - Book of Abstracts, Niš, Serbia, June 8-9, 2024
T1  - The influence of suspension concentration on the pHmax – pHmin range during the solubility determination
T1  - Ispitivanje uticaja koncentracije suspenzije na širinu pHmax – pHmin opsega tokom određivanja rastvorljivosti
SP  - 47
EP  - 47
UR  - https://hdl.handle.net/21.15107/rcub_cer_7656
ER  - 

@conference{
author = "Marković, Olivera and Mrđinac, Jelena Ž. and Pepić, Sara and Verbić, Tatjana",
year = "2024",
abstract = "The solubility profile of a drug typically consists of two independent curves that intersect 
at a specific point called pHmax. At pHmax, both salt and base coexist as solid phases. While 
two solids coexist, pH and solubility in the heterogeneous system remain constant 
(according to the Gibbs Phase Rule). Recent studies, however, have shown that pH and 
solubility might change during the salt-to-free-base transformation. This pH range, 
containing two solids, is termed the pHmax – pHmin range. pHmax refers to the pH value at 
the maximum solubility of a eutectic mixture, whereas pHmin represents the pH value at the 
minimum solubility of the eutectic mixture. The objective of this study was to investigate 
the influence of suspension concentration (the ratio of drug mass to suspension volume) on 
the pHmax – pHmin range during solubility determination using the pH-Ramp shake-flask
method. Nortriptyline hydrochloride (Nor, monoprotic base) and atorvastatin calcium (At, 
monoprotic acid) were employed as model compounds. Results indicate that the pHmax –
pHmin range increases as suspension concentration rises (for 20.10 mg NorHCl/mL: 
pHmax=3.55, ΔpH=0; for 59.82 mg NorHCl/mL: pHmax – pHmin= 3.56 – 4.52, ΔpH=0.96). 
Understanding the details of the pHmax – pHmin range could significantly impact product 
formulation optimization in drug research., Cilj ovog rada bio je ispitivanje uticaja koncentracije suspenzije na širinu pHmax – pHmin
opsega tokom određivanja rastvorljivosti pH-Ramp shake-flask metodom. Kao model 
jedinjenja izabrani su nortriptilin-hidrohlorid i atorvastatin-kalcijum. Rezultati su pokazali 
da sa porastom koncentracije suspenzije dolazi do širenja opsega pHmax – pHmin, a ovakva 
proučavanja mogu značajno doprineti optimizaciji formulacije u procesu dizajna i razvoja 
lekova.",
publisher = "Serbian Chemical Society",
journal = "60th Meeting of the Serbian Chemical Society - Book of Abstracts, Niš, Serbia, June 8-9, 2024",
title = "The influence of suspension concentration on the pHmax – pHmin range during the solubility determination, Ispitivanje uticaja koncentracije suspenzije na širinu pHmax – pHmin opsega tokom određivanja rastvorljivosti",
pages = "47-47",
url = "https://hdl.handle.net/21.15107/rcub_cer_7656"
}

Marković, O., Mrđinac, J. Ž., Pepić, S.,& Verbić, T.. (2024). The influence of suspension concentration on the pHmax – pHmin range during the solubility determination. in 60th Meeting of the Serbian Chemical Society - Book of Abstracts, Niš, Serbia, June 8-9, 2024
Serbian Chemical Society., 47-47.
https://hdl.handle.net/21.15107/rcub_cer_7656

Marković O, Mrđinac JŽ, Pepić S, Verbić T. The influence of suspension concentration on the pHmax – pHmin range during the solubility determination. in 60th Meeting of the Serbian Chemical Society - Book of Abstracts, Niš, Serbia, June 8-9, 2024. 2024;:47-47.
https://hdl.handle.net/21.15107/rcub_cer_7656 .

Marković, Olivera, Mrđinac, Jelena Ž., Pepić, Sara, Verbić, Tatjana, "The influence of suspension concentration on the pHmax – pHmin range during the solubility determination" in 60th Meeting of the Serbian Chemical Society - Book of Abstracts, Niš, Serbia, June 8-9, 2024 (2024):47-47,
https://hdl.handle.net/21.15107/rcub_cer_7656 .

TY  - CONF
AU  - Mrđinac, Jelena Ž.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana Ž.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5398
AB  - The ionization constant (usually expressed in logarithmic form, pKa) is important physicochemical parameter which is used to characterize the acid-base chemistry of a compound. Since most drugs contain one or more ionizable functional groups, knowledge of pKa values is necessary in drug research. The most common techniques used for pKa determination are potentiometry and spectrophotometry. Potentiometry is a method of choice when ionization processes are overlapping, as in such case it is not possible to obtain the absorption spectrum of each species present in solution. The aim of this work was the comparative analysis of pKa determination using potentiometry and spectrophotometry for model compounds with overlapping ionization processes: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. The potentiometric titrations were performed with pSOL Model 3 instrument (pION) equipped with pS software package for titration data analysis.1 Avdeef–Bucher four–parameter equation was used for electrode standardization.2 To overcome the above-mentioned limitation of spectrophotometry, the alternative approach was applied in this study. The new aminocaproate phosphate buffer (containing phosphoric and ε-aminocaproic acids) was used for the solutions preparation of the model compounds in pH range 1 – 12. This buffer has numerous advantages like UV-transparency, resistance to pH changes upon standing for several days, useful buffer capacity and constant ionic strength in the wide range of pH values. Absorption spectra were recorded according to specific procedure which was carefully designed to avoid systematic errors. Collected absorption spectra will be used for the development of the algorithm for the spectral deconvolution (using MATLAB). Such software can be very useful tool in the drug research, especially for the analysis of the compounds which pKa values cannot be determined by potentiometry.
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  - Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine
SP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_cer_5398
ER  - 

@conference{
author = "Mrđinac, Jelena Ž. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana Ž.",
year = "2022",
abstract = "The ionization constant (usually expressed in logarithmic form, pKa) is important physicochemical parameter which is used to characterize the acid-base chemistry of a compound. Since most drugs contain one or more ionizable functional groups, knowledge of pKa values is necessary in drug research. The most common techniques used for pKa determination are potentiometry and spectrophotometry. Potentiometry is a method of choice when ionization processes are overlapping, as in such case it is not possible to obtain the absorption spectrum of each species present in solution. The aim of this work was the comparative analysis of pKa determination using potentiometry and spectrophotometry for model compounds with overlapping ionization processes: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. The potentiometric titrations were performed with pSOL Model 3 instrument (pION) equipped with pS software package for titration data analysis.1 Avdeef–Bucher four–parameter equation was used for electrode standardization.2 To overcome the above-mentioned limitation of spectrophotometry, the alternative approach was applied in this study. The new aminocaproate phosphate buffer (containing phosphoric and ε-aminocaproic acids) was used for the solutions preparation of the model compounds in pH range 1 – 12. This buffer has numerous advantages like UV-transparency, resistance to pH changes upon standing for several days, useful buffer capacity and constant ionic strength in the wide range of pH values. Absorption spectra were recorded according to specific procedure which was carefully designed to avoid systematic errors. Collected absorption spectra will be used for the development of the algorithm for the spectral deconvolution (using MATLAB). Such software can be very useful tool in the drug research, especially for the analysis of the compounds which pKa values cannot be determined by potentiometry.",
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 = "Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine",
pages = "42",
url = "https://hdl.handle.net/21.15107/rcub_cer_5398"
}

Mrđinac, J. Ž., Marković, O. S., Pešić, M. P.,& Verbić, T. Ž.. (2022). Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
Belgrade : Serbian Chemical Society., 42.
https://hdl.handle.net/21.15107/rcub_cer_5398

Mrđinac JŽ, Marković OS, Pešić MP, Verbić TŽ. Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. 2022;:42.
https://hdl.handle.net/21.15107/rcub_cer_5398 .

Mrđinac, Jelena Ž., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana Ž., "Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine" in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 (2022):42,
https://hdl.handle.net/21.15107/rcub_cer_5398 .