TY  - CONF
AU  - Marković, Olivera S.
AU  - Gajić, Brankica P.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana Ž.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5396
AB  - Experimental studies of solubility are important in all phases of drug design and development. Solubility data are used to screen out drug-like candidates, biopharmaceutical classification and formulation optimization. The development of oral and parenteral dosage forms can be challenging, especially when drugs are poorly soluble, ionizable, exhibiting pH-dependent solubility and when multiple counterions are present in drug suspension. The influence of different counterions on the existing equilibria and on pH-dependent drug solubility must be defined in such systems. To investigate the effect of multiple ions on the solubility of a model basic drug – tricyclic antidepressant imipramine (Im), we conducted a systematic study of the Im solubility as a function of pH in the presence of both chloride and phosphate ions as well as in chloride-free and phosphate-free suspensions. The pH–Ramp shake–flask method1,2 was used for solubility determination. The computer program pDISOL–X was used for data analysis. It is shown that distinct pH-dependent solubility profiles were obtained in studied systems. Depending on the pH and the total concentration of chloride and/or phosphate ions, Im can precipitate as chloride and phosphate salt or free base. Furthermore, pH values of solid phase transitions (pHmax) varied as well. For instance, pHmax of solid phase transition of (ImH)H2PO4(s) to (ImH)2HPO4(s) change from 5.15 (chloride and phosphate-containing suspensions) to 5.73 (chloride-free suspensions). The intensive self-aggregation of Im in acidic region was suppressed by raising chloride or phosphate ions concentration (Iavg 1.42–1.64 M). In that way, solubility of Im was decreased due to the common-ion effect. This study illustrates the influence of competing counterions on Im solubility and on interconversions in solid phase. Hence, such factors must be taken into account during formulation optimization in drug research.
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 influence of competing counterions on the solubility of imipramine
SP  - 27
UR  - https://hdl.handle.net/21.15107/rcub_cer_5396
ER  - 

@conference{
author = "Marković, Olivera S. and Gajić, Brankica P. and Pešić, Miloš P. and Verbić, Tatjana Ž.",
year = "2022",
abstract = "Experimental studies of solubility are important in all phases of drug design and development. Solubility data are used to screen out drug-like candidates, biopharmaceutical classification and formulation optimization. The development of oral and parenteral dosage forms can be challenging, especially when drugs are poorly soluble, ionizable, exhibiting pH-dependent solubility and when multiple counterions are present in drug suspension. The influence of different counterions on the existing equilibria and on pH-dependent drug solubility must be defined in such systems. To investigate the effect of multiple ions on the solubility of a model basic drug – tricyclic antidepressant imipramine (Im), we conducted a systematic study of the Im solubility as a function of pH in the presence of both chloride and phosphate ions as well as in chloride-free and phosphate-free suspensions. The pH–Ramp shake–flask method1,2 was used for solubility determination. The computer program pDISOL–X was used for data analysis. It is shown that distinct pH-dependent solubility profiles were obtained in studied systems. Depending on the pH and the total concentration of chloride and/or phosphate ions, Im can precipitate as chloride and phosphate salt or free base. Furthermore, pH values of solid phase transitions (pHmax) varied as well. For instance, pHmax of solid phase transition of (ImH)H2PO4(s) to (ImH)2HPO4(s) change from 5.15 (chloride and phosphate-containing suspensions) to 5.73 (chloride-free suspensions). The intensive self-aggregation of Im in acidic region was suppressed by raising chloride or phosphate ions concentration (Iavg 1.42–1.64 M). In that way, solubility of Im was decreased due to the common-ion effect. This study illustrates the influence of competing counterions on Im solubility and on interconversions in solid phase. Hence, such factors must be taken into account during formulation optimization in drug research.",
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 influence of competing counterions on the solubility of imipramine",
pages = "27",
url = "https://hdl.handle.net/21.15107/rcub_cer_5396"
}

Marković, O. S., Gajić, B. P., Pešić, M. P.,& Verbić, T. Ž.. (2022). The influence of competing counterions on the solubility of imipramine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
Belgrade : Serbian Chemical Society., 27.
https://hdl.handle.net/21.15107/rcub_cer_5396

Marković OS, Gajić BP, Pešić MP, Verbić TŽ. The influence of competing counterions on the solubility of imipramine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. 2022;:27.
https://hdl.handle.net/21.15107/rcub_cer_5396 .

Marković, Olivera S., Gajić, Brankica P., Pešić, Miloš P., Verbić, Tatjana Ž., "The influence of competing counterions on the solubility of imipramine" in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 (2022):27,
https://hdl.handle.net/21.15107/rcub_cer_5396 .

TY  - CONF
AU  - Marković, Olivera
AU  - Gajić, Brankica P.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana Ž.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5087
AB  - Cilj ovog rada bio je proučavanje ravnoteža u heterogenim sistemima tricikličnog 
antidepresiva amitriptilina (Am) koji sadrže hloride i/ili fosfate. Rastvorljivost Am u 
uslovima povećane jonske sile određena je pH–Ramp shake–flask metodom. Veća 
rastvorljivost Am u kiseloj sredini od očekivane, posledica je agregacije – analiza 
eksperimentalnih podataka pomoću programa pDISOL–XTM ukazuje na verovatno 
građenje pentamera Am5H5 5+. Kritična micelarna koncentracija i stepen disocijacije 
agregata određeni su primenom konduktometrijskih titracija. U baznoj sredini primećena je 
delimična degradacija Am. Eksperimentalno dobijeni podaci o rastvorljivosti biološki 
aktivnih supstanci i postojećim ravnotežama u heterogenim sistemima važni su u svim 
fazama dizajna i razvoja lekova.
AB  - The aim of this work was to study the equilibria in tricyclic antidepressant amitriptyline 
(Am) heterogeneous systems containing chloride and/or phosphate ions. Solubility of Am 
in high ionic strength conditions was determined using pH–Ramp shake–flask method.1, 2
Higher solubility of Am than expected in an acidic media is a consequence of self-aggregation – pentamer formation (Am5H5 5+) according to pDISOL–XTM analysis. Critical 
micelle concentration and the degree of the aggregate dissociation were determined by 
conductometric titrations. Partial degradation of Am in alkaline suspensions was observed. 
Experimental studies of solubility as well as the existing equilibria in heterogeneous 
systems of biologically active compounds are important at all stages of drug design and 
development.
PB  - Belgrade : Serbian Chemical Society
C3  - Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine
T1  - Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina
T1  - Study of equilibria in heterogeneous systems of tricyclic  antidepressant amitriptyline
SP  - 53
EP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_cer_5087
ER  - 

@conference{
author = "Marković, Olivera and Gajić, Brankica P. and Pešić, Miloš P. and Verbić, Tatjana Ž.",
year = "2022",
abstract = "Cilj ovog rada bio je proučavanje ravnoteža u heterogenim sistemima tricikličnog 
antidepresiva amitriptilina (Am) koji sadrže hloride i/ili fosfate. Rastvorljivost Am u 
uslovima povećane jonske sile određena je pH–Ramp shake–flask metodom. Veća 
rastvorljivost Am u kiseloj sredini od očekivane, posledica je agregacije – analiza 
eksperimentalnih podataka pomoću programa pDISOL–XTM ukazuje na verovatno 
građenje pentamera Am5H5 5+. Kritična micelarna koncentracija i stepen disocijacije 
agregata određeni su primenom konduktometrijskih titracija. U baznoj sredini primećena je 
delimična degradacija Am. Eksperimentalno dobijeni podaci o rastvorljivosti biološki 
aktivnih supstanci i postojećim ravnotežama u heterogenim sistemima važni su u svim 
fazama dizajna i razvoja lekova., The aim of this work was to study the equilibria in tricyclic antidepressant amitriptyline 
(Am) heterogeneous systems containing chloride and/or phosphate ions. Solubility of Am 
in high ionic strength conditions was determined using pH–Ramp shake–flask method.1, 2
Higher solubility of Am than expected in an acidic media is a consequence of self-aggregation – pentamer formation (Am5H5 5+) according to pDISOL–XTM analysis. Critical 
micelle concentration and the degree of the aggregate dissociation were determined by 
conductometric titrations. Partial degradation of Am in alkaline suspensions was observed. 
Experimental studies of solubility as well as the existing equilibria in heterogeneous 
systems of biologically active compounds are important at all stages of drug design and 
development.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine",
title = "Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina, Study of equilibria in heterogeneous systems of tricyclic  antidepressant amitriptyline",
pages = "53-53",
url = "https://hdl.handle.net/21.15107/rcub_cer_5087"
}

Marković, O., Gajić, B. P., Pešić, M. P.,& Verbić, T. Ž.. (2022). Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina. in Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine
Belgrade : Serbian Chemical Society., 53-53.
https://hdl.handle.net/21.15107/rcub_cer_5087

Marković O, Gajić BP, Pešić MP, Verbić TŽ. Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina. in Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine. 2022;:53-53.
https://hdl.handle.net/21.15107/rcub_cer_5087 .

Marković, Olivera, Gajić, Brankica P., Pešić, Miloš P., Verbić, Tatjana Ž., "Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina" in Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine (2022):53-53,
https://hdl.handle.net/21.15107/rcub_cer_5087 .