Pepić, Sara

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The influence of suspension concentration on the pHmax – pHmin range during the solubility determination

Marković, Olivera; Mrđinac, Jelena Ž.; Pepić, Sara; Verbić, Tatjana

(Serbian Chemical Society, 2024)

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 .