TY  - JOUR
AU  - Tasić, Gordana
AU  - Mitrović, Nikola
AU  - Simić, Milena
AU  - Koravović, Mladen
AU  - Jovanović, Predrag
AU  - Petković, Miloš
AU  - Jovanović, Miloš
AU  - Ivković, Branka
AU  - Savić, Vladimir
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5556
AB  - Hydantoin derivatives are versatile structural motifs found in natural products
and various compounds with different biological or other properties. Due to
their importance in both organic and medicinal chemistry, a number of synthetic procedures have been developed. In this article, a novel methodology
utilizing N-Boc protected amino acid amides for their preparation has been
described. The cyclisation process was accomplished using solid supported
PPh3 and CBr 4 as reagents affording substituted hydantoins in moderate to
good yields (40%–77%).
PB  - Wiley Periodicals LLC.
T2  - Journal Heterocyclic Chemistry
T1  - Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent
DO  - 10.1002/jhet.4802
ER  - 

@article{
author = "Tasić, Gordana and Mitrović, Nikola and Simić, Milena and Koravović, Mladen and Jovanović, Predrag and Petković, Miloš and Jovanović, Miloš and Ivković, Branka and Savić, Vladimir",
year = "2024",
abstract = "Hydantoin derivatives are versatile structural motifs found in natural products
and various compounds with different biological or other properties. Due to
their importance in both organic and medicinal chemistry, a number of synthetic procedures have been developed. In this article, a novel methodology
utilizing N-Boc protected amino acid amides for their preparation has been
described. The cyclisation process was accomplished using solid supported
PPh3 and CBr 4 as reagents affording substituted hydantoins in moderate to
good yields (40%–77%).",
publisher = "Wiley Periodicals LLC.",
journal = "Journal Heterocyclic Chemistry",
title = "Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent",
doi = "10.1002/jhet.4802"
}

Tasić, G., Mitrović, N., Simić, M., Koravović, M., Jovanović, P., Petković, M., Jovanović, M., Ivković, B.,& Savić, V.. (2024). Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent. in Journal Heterocyclic Chemistry
Wiley Periodicals LLC...
https://doi.org/10.1002/jhet.4802

Tasić G, Mitrović N, Simić M, Koravović M, Jovanović P, Petković M, Jovanović M, Ivković B, Savić V. Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent. in Journal Heterocyclic Chemistry. 2024;.
doi:10.1002/jhet.4802 .

Tasić, Gordana, Mitrović, Nikola, Simić, Milena, Koravović, Mladen, Jovanović, Predrag, Petković, Miloš, Jovanović, Miloš, Ivković, Branka, Savić, Vladimir, "Synthesis of hydantoins from N-Boc protected aminoacid derived amides using polymer-supported PPh3/CBr4as a reagent" in Journal Heterocyclic Chemistry (2024),
https://doi.org/10.1002/jhet.4802 . .

TY  - JOUR
AU  - Ivković, Branka
AU  - Milutinović, Ivana
AU  - Čudina, Olivera
AU  - Marković, Bojan
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4086
AB  - Gentamicin sulfate is a potent broad spectrum aminoglycoside antibiotic which is used against Gram- positive and Gram-negative bacteria. A simple, isocratic HPLC method for separation, identification and determination of gentamicin and parabens (methylparaben and propylparaben) was developed and validated. To our knowledge there is no report about simultaneous determination of those three ana- lytes in pharmaceutical products. The optimum chromatographic conditions were achieved on CN column with a mobile phase consisting of 0.15% triethylamine in 10 mM KH 2 PO4 aqueous solution (final pH 3.0 adjusted with H 3 PO 4 ) and methanol in the ratio 70:30 (v/v), providing selective quan- tification of analytes within 5 min. The method was successfully validated according to ICH guidelines acceptance criteria in terms of selectivity, linearity, accuracy, precision and robustness. The linearity of the method was proved in defined concentrations ranges for gentamicin (0.32–1.04 mg mL1 ), meth- ylparaben (0.0072–0.0234 mg mL1 ) and propylparaben (0.0008–0.0026 mg mL1 ). Relative standard deviations calculated for all analytes in precision testing were <2% (analysis repeatability) and <3% (intermediate precision). Recovery values were between 98.87% and 101.67%. Chromatographic pa- rameters are not significantly influenced by small variations of column temperature, pH and molarity of KH2 PO 4 . Finally, the method was successfully applied for quantitative determination of gentamicin and parabens in commercially available solution for injection. Proposed HPLC method is found to be promising in terms of simplicity, analysis times and non-use of derivatization and ion-pair agents.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben
VL  - 35
IS  - 1
SP  - 81
EP  - 87
DO  - 10.1556/1326.2022.00999
ER  - 

@article{
author = "Ivković, Branka and Milutinović, Ivana and Čudina, Olivera and Marković, Bojan",
year = "2023",
abstract = "Gentamicin sulfate is a potent broad spectrum aminoglycoside antibiotic which is used against Gram- positive and Gram-negative bacteria. A simple, isocratic HPLC method for separation, identification and determination of gentamicin and parabens (methylparaben and propylparaben) was developed and validated. To our knowledge there is no report about simultaneous determination of those three ana- lytes in pharmaceutical products. The optimum chromatographic conditions were achieved on CN column with a mobile phase consisting of 0.15% triethylamine in 10 mM KH 2 PO4 aqueous solution (final pH 3.0 adjusted with H 3 PO 4 ) and methanol in the ratio 70:30 (v/v), providing selective quan- tification of analytes within 5 min. The method was successfully validated according to ICH guidelines acceptance criteria in terms of selectivity, linearity, accuracy, precision and robustness. The linearity of the method was proved in defined concentrations ranges for gentamicin (0.32–1.04 mg mL1 ), meth- ylparaben (0.0072–0.0234 mg mL1 ) and propylparaben (0.0008–0.0026 mg mL1 ). Relative standard deviations calculated for all analytes in precision testing were <2% (analysis repeatability) and <3% (intermediate precision). Recovery values were between 98.87% and 101.67%. Chromatographic pa- rameters are not significantly influenced by small variations of column temperature, pH and molarity of KH2 PO 4 . Finally, the method was successfully applied for quantitative determination of gentamicin and parabens in commercially available solution for injection. Proposed HPLC method is found to be promising in terms of simplicity, analysis times and non-use of derivatization and ion-pair agents.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben",
volume = "35",
number = "1",
pages = "81-87",
doi = "10.1556/1326.2022.00999"
}

Ivković, B., Milutinović, I., Čudina, O.,& Marković, B.. (2023). A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben. in Acta Chromatographica
Akademiai Kiado ZRt.., 35(1), 81-87.
https://doi.org/10.1556/1326.2022.00999

Ivković B, Milutinović I, Čudina O, Marković B. A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben. in Acta Chromatographica. 2023;35(1):81-87.
doi:10.1556/1326.2022.00999 .

Ivković, Branka, Milutinović, Ivana, Čudina, Olivera, Marković, Bojan, "A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben" in Acta Chromatographica, 35, no. 1 (2023):81-87,
https://doi.org/10.1556/1326.2022.00999 . .

TY  - JOUR
AU  - Selaković, Milan
AU  - Aleksić, Mara
AU  - Kotur-Stevuljević, Jelena
AU  - Rupar, Jelena
AU  - Ivković, Branka
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4550
AB  - Ivermectin (IVM) is a drug from the group of anthelmintics used in veterinary and human medicine. Recently, interest in IVM has increased as it has been used for the treatment of some malignant diseases, as well as viral infections caused by the Zika virus, HIV-1 and SARS-CoV-2. The electrochemical behaviour of IVM was investigated using cyclic (CV), differential pulse (DPV) and square wave voltammetry (SWV) at glassy carbon electrode (GCE). IVM showed independent oxidation and reduction processes. The effect of pH and scan rate indicated the irreversibility of all processes and confirmed the diffusion character of oxidation and reduction as an adsorption-controlled process. Mechanisms for IVM oxidation at the tetrahydrofuran ring and reduction of the 1,4-diene structure in the IVM molecule are proposed. The redox behaviour of IVM in a biological matrix (human serum pool) showed a pronounced antioxidant potential similar to that of Trolox during short incubation, whereas a prolonged stay among biomolecules and in the presence of an exogenous pro-oxidant (tert-butyl hydroperoxide, TBH) resulted in a loss of its antioxidant effect. The antioxidant potential of IVM was confirmed by voltametric methodology which is proposed for the first time.
PB  - MDPI
T2  - Molecules
T1  - Electrochemical Characterisation and Confirmation of Antioxidative Properties of Ivermectin in Biological Medium
VL  - 28
IS  - 5
DO  - 10.3390/molecules28052113
ER  - 

@article{
author = "Selaković, Milan and Aleksić, Mara and Kotur-Stevuljević, Jelena and Rupar, Jelena and Ivković, Branka",
year = "2023",
abstract = "Ivermectin (IVM) is a drug from the group of anthelmintics used in veterinary and human medicine. Recently, interest in IVM has increased as it has been used for the treatment of some malignant diseases, as well as viral infections caused by the Zika virus, HIV-1 and SARS-CoV-2. The electrochemical behaviour of IVM was investigated using cyclic (CV), differential pulse (DPV) and square wave voltammetry (SWV) at glassy carbon electrode (GCE). IVM showed independent oxidation and reduction processes. The effect of pH and scan rate indicated the irreversibility of all processes and confirmed the diffusion character of oxidation and reduction as an adsorption-controlled process. Mechanisms for IVM oxidation at the tetrahydrofuran ring and reduction of the 1,4-diene structure in the IVM molecule are proposed. The redox behaviour of IVM in a biological matrix (human serum pool) showed a pronounced antioxidant potential similar to that of Trolox during short incubation, whereas a prolonged stay among biomolecules and in the presence of an exogenous pro-oxidant (tert-butyl hydroperoxide, TBH) resulted in a loss of its antioxidant effect. The antioxidant potential of IVM was confirmed by voltametric methodology which is proposed for the first time.",
publisher = "MDPI",
journal = "Molecules",
title = "Electrochemical Characterisation and Confirmation of Antioxidative Properties of Ivermectin in Biological Medium",
volume = "28",
number = "5",
doi = "10.3390/molecules28052113"
}

Selaković, M., Aleksić, M., Kotur-Stevuljević, J., Rupar, J.,& Ivković, B.. (2023). Electrochemical Characterisation and Confirmation of Antioxidative Properties of Ivermectin in Biological Medium. in Molecules
MDPI., 28(5).
https://doi.org/10.3390/molecules28052113

Selaković M, Aleksić M, Kotur-Stevuljević J, Rupar J, Ivković B. Electrochemical Characterisation and Confirmation of Antioxidative Properties of Ivermectin in Biological Medium. in Molecules. 2023;28(5).
doi:10.3390/molecules28052113 .

Selaković, Milan, Aleksić, Mara, Kotur-Stevuljević, Jelena, Rupar, Jelena, Ivković, Branka, "Electrochemical Characterisation and Confirmation of Antioxidative Properties of Ivermectin in Biological Medium" in Molecules, 28, no. 5 (2023),
https://doi.org/10.3390/molecules28052113 . .

TY  - CONF
AU  - Marić, M.
AU  - Ivković, A.
AU  - Ivković, Branka
AU  - Janošević-Ležaić, Aleksandra
AU  - Uskoković-Marković, Snežana
AU  - Savić, J.
AU  - Milojević-Rakić, M.
AU  - Bajuk-Bogdanović, D.
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5448
AB  - ABSTRACT – Organic dyes from industry wastewater pollute water tables. Here proposed environmental 
solution relies on pristine red soil for oxidative degradation of methylene blue dye. Soil analysis comprised 
spectroscopic (FTIR and Raman) and microscopic (SEM/EDS) techniques, while spectrophotometry was 
applied for dye quantification. The dominant soil mineral is kaolinite, while Fe homogeneous distribution 
is witnessed in the γ-FeO(OH) form. Soil/Fenton reagent achieved substantial 93% dye removal. An optimal 
oxidant concentration in the Fenton system is 10 mM. We confirm the excellent performance of pristine 
red soil samples as naturally occurring adsorbents and catalysts in Fenton oxidation of environmental 
pollutants.
PB  - University of Belgrade
PB  - Technical Faculty in Bor
C3  - XV International Mineral Processing and Recycling Conference, 17-19 May 2023, Belgrade, Serbia
T1  - Removal of methylene blue from aqueous solutions using an iron-rich soil
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5448
ER  - 

@conference{
author = "Marić, M. and Ivković, A. and Ivković, Branka and Janošević-Ležaić, Aleksandra and Uskoković-Marković, Snežana and Savić, J. and Milojević-Rakić, M. and Bajuk-Bogdanović, D.",
year = "2023",
abstract = "ABSTRACT – Organic dyes from industry wastewater pollute water tables. Here proposed environmental 
solution relies on pristine red soil for oxidative degradation of methylene blue dye. Soil analysis comprised 
spectroscopic (FTIR and Raman) and microscopic (SEM/EDS) techniques, while spectrophotometry was 
applied for dye quantification. The dominant soil mineral is kaolinite, while Fe homogeneous distribution 
is witnessed in the γ-FeO(OH) form. Soil/Fenton reagent achieved substantial 93% dye removal. An optimal 
oxidant concentration in the Fenton system is 10 mM. We confirm the excellent performance of pristine 
red soil samples as naturally occurring adsorbents and catalysts in Fenton oxidation of environmental 
pollutants.",
publisher = "University of Belgrade, Technical Faculty in Bor",
journal = "XV International Mineral Processing and Recycling Conference, 17-19 May 2023, Belgrade, Serbia",
title = "Removal of methylene blue from aqueous solutions using an iron-rich soil",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5448"
}

Marić, M., Ivković, A., Ivković, B., Janošević-Ležaić, A., Uskoković-Marković, S., Savić, J., Milojević-Rakić, M.,& Bajuk-Bogdanović, D.. (2023). Removal of methylene blue from aqueous solutions using an iron-rich soil. in XV International Mineral Processing and Recycling Conference, 17-19 May 2023, Belgrade, Serbia
University of Belgrade..
https://hdl.handle.net/21.15107/rcub_farfar_5448

Marić M, Ivković A, Ivković B, Janošević-Ležaić A, Uskoković-Marković S, Savić J, Milojević-Rakić M, Bajuk-Bogdanović D. Removal of methylene blue from aqueous solutions using an iron-rich soil. in XV International Mineral Processing and Recycling Conference, 17-19 May 2023, Belgrade, Serbia. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_5448 .

Marić, M., Ivković, A., Ivković, Branka, Janošević-Ležaić, Aleksandra, Uskoković-Marković, Snežana, Savić, J., Milojević-Rakić, M., Bajuk-Bogdanović, D., "Removal of methylene blue from aqueous solutions using an iron-rich soil" in XV International Mineral Processing and Recycling Conference, 17-19 May 2023, Belgrade, Serbia (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5448 .

TY  - JOUR
AU  - Subošić, Branko
AU  - Kotur-Stevuljević, Jelena
AU  - Brborić, Jasmina
AU  - Janković, Tamara
AU  - Milenković, Marina
AU  - Ivković, Branka
AU  - Kostadinović, Jelena
AU  - Savić, Jelena
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5146
AB  - The interplay between oxidative stress and inflammation is implicated in many chronic diseases including Alzheimer`s disease, cardiovascular diseases, diabetes and cancer. Thirteen β-hydroxy-β-arylalkanoic acids were previously synthesized and evaluated for their anti-inflammatory activity. The aim of this study was to asses ex vivo antioxidant activity of synthesized acids, as well as ibuprofen and to identify the compounds with the most promising results for further investigation on their capacity to counteract in vivo oxidative stress triggered by inflammation. The antioxidant potential of tested compounds was evaluated by determining the concentrations of total antioxidative status, total oxidative status, prooxidant antioxidant balance and the total sulfhydryl groups. Z score statistics were used to calculate the summary scores for antioxidative activity, prooxidative activity and oxy score. The tested compounds and ibuprofen demonstrated mild prooxidative activity ex vivo. Seven acids with substituents on one benzene ring exhibited better results than ibuprofen and were selected for in vivo testing. In vivo results demonstrated better antioxidant protection compared to ex vivo results. Compound g which contains nitro group on the benzene ring demonstrated the lowest oxy score, and four compounds exhibited better results than ibuprofen.
PB  - Pakistan Journal of Pharmaceutical Sciences
T2  - Pakistan Journal of Pharmaceutical Sciences
T1  - Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids
VL  - 36
IS  - 5
SP  - 1367
EP  - 1374
DO  - 10.36721/PJPS.2023.36.5.REG.1367-1374.1
ER  - 

@article{
author = "Subošić, Branko and Kotur-Stevuljević, Jelena and Brborić, Jasmina and Janković, Tamara and Milenković, Marina and Ivković, Branka and Kostadinović, Jelena and Savić, Jelena",
year = "2023",
abstract = "The interplay between oxidative stress and inflammation is implicated in many chronic diseases including Alzheimer`s disease, cardiovascular diseases, diabetes and cancer. Thirteen β-hydroxy-β-arylalkanoic acids were previously synthesized and evaluated for their anti-inflammatory activity. The aim of this study was to asses ex vivo antioxidant activity of synthesized acids, as well as ibuprofen and to identify the compounds with the most promising results for further investigation on their capacity to counteract in vivo oxidative stress triggered by inflammation. The antioxidant potential of tested compounds was evaluated by determining the concentrations of total antioxidative status, total oxidative status, prooxidant antioxidant balance and the total sulfhydryl groups. Z score statistics were used to calculate the summary scores for antioxidative activity, prooxidative activity and oxy score. The tested compounds and ibuprofen demonstrated mild prooxidative activity ex vivo. Seven acids with substituents on one benzene ring exhibited better results than ibuprofen and were selected for in vivo testing. In vivo results demonstrated better antioxidant protection compared to ex vivo results. Compound g which contains nitro group on the benzene ring demonstrated the lowest oxy score, and four compounds exhibited better results than ibuprofen.",
publisher = "Pakistan Journal of Pharmaceutical Sciences",
journal = "Pakistan Journal of Pharmaceutical Sciences",
title = "Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids",
volume = "36",
number = "5",
pages = "1367-1374",
doi = "10.36721/PJPS.2023.36.5.REG.1367-1374.1"
}

Subošić, B., Kotur-Stevuljević, J., Brborić, J., Janković, T., Milenković, M., Ivković, B., Kostadinović, J.,& Savić, J.. (2023). Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids. in Pakistan Journal of Pharmaceutical Sciences
Pakistan Journal of Pharmaceutical Sciences., 36(5), 1367-1374.
https://doi.org/10.36721/PJPS.2023.36.5.REG.1367-1374.1

Subošić B, Kotur-Stevuljević J, Brborić J, Janković T, Milenković M, Ivković B, Kostadinović J, Savić J. Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids. in Pakistan Journal of Pharmaceutical Sciences. 2023;36(5):1367-1374.
doi:10.36721/PJPS.2023.36.5.REG.1367-1374.1 .

Subošić, Branko, Kotur-Stevuljević, Jelena, Brborić, Jasmina, Janković, Tamara, Milenković, Marina, Ivković, Branka, Kostadinović, Jelena, Savić, Jelena, "Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids" in Pakistan Journal of Pharmaceutical Sciences, 36, no. 5 (2023):1367-1374,
https://doi.org/10.36721/PJPS.2023.36.5.REG.1367-1374.1 . .

TY  - CONF
AU  - Adamov, Ivana
AU  - Medarević, Đorđe
AU  - Pešić, Nikola
AU  - Ivković, Branka
AU  - Kočović, David
AU  - Grujić, Branka
AU  - Ibrić, Svetlana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5335
AB  - Trodimenzionalna (3D) štampa predstavlja inovativnu tehnologiju u oblasti farmacije, koja ima potencijal da obezbedi proizvodnju malih serija lekova prilagođenih individualnim potrebama pacijenata. Intenzivno istraživanje u oblasti 3D štampe rezultovalo je razvojem velikog broj različitih tehnika, a čija osnovna, zajednička karakteristika jeste štampanje u slojevima. ...
AB  - Three-dimensional (3D) printing is an innovative technology in the field of pharmacy with potential to provide manufacturing of small batches of patient-taiIored medicines. Intensive research in the field of 3D printing has resulted in development of numerous different techniques whose common feature is printing in layers The aim of this study was to formulate and comparatively characterize orodispersible tablets (ODTs) of desloratadine (DSL) obtained by 3D selective laser sintering (SLS) technique with commercially available ODTs. ...
PB  - Farmaceutska komora Crne Gore
PB  - Univerzitet Crne Gore, Medicinski fakultet, studijski program-farmacija
C3  - 4. kongres farmaceuta Crne Gore sa međunarodnim učešćem, 11-14. maj 2023. Budva, Bečići, Crna Gora, Zbornik sažetaka
T1  - Formulacija i karakterizacija oralno-disperzibilnih tableta desloratadina dobijenih 3D tehnikom selektivnog laserskog sinterovanja
VL  - PP-12
SP  - 104
EP  - 105
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5335
ER  - 

@conference{
author = "Adamov, Ivana and Medarević, Đorđe and Pešić, Nikola and Ivković, Branka and Kočović, David and Grujić, Branka and Ibrić, Svetlana",
year = "2023",
abstract = "Trodimenzionalna (3D) štampa predstavlja inovativnu tehnologiju u oblasti farmacije, koja ima potencijal da obezbedi proizvodnju malih serija lekova prilagođenih individualnim potrebama pacijenata. Intenzivno istraživanje u oblasti 3D štampe rezultovalo je razvojem velikog broj različitih tehnika, a čija osnovna, zajednička karakteristika jeste štampanje u slojevima. ..., Three-dimensional (3D) printing is an innovative technology in the field of pharmacy with potential to provide manufacturing of small batches of patient-taiIored medicines. Intensive research in the field of 3D printing has resulted in development of numerous different techniques whose common feature is printing in layers The aim of this study was to formulate and comparatively characterize orodispersible tablets (ODTs) of desloratadine (DSL) obtained by 3D selective laser sintering (SLS) technique with commercially available ODTs. ...",
publisher = "Farmaceutska komora Crne Gore, Univerzitet Crne Gore, Medicinski fakultet, studijski program-farmacija",
journal = "4. kongres farmaceuta Crne Gore sa međunarodnim učešćem, 11-14. maj 2023. Budva, Bečići, Crna Gora, Zbornik sažetaka",
title = "Formulacija i karakterizacija oralno-disperzibilnih tableta desloratadina dobijenih 3D tehnikom selektivnog laserskog sinterovanja",
volume = "PP-12",
pages = "104-105",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5335"
}

Adamov, I., Medarević, Đ., Pešić, N., Ivković, B., Kočović, D., Grujić, B.,& Ibrić, S.. (2023). Formulacija i karakterizacija oralno-disperzibilnih tableta desloratadina dobijenih 3D tehnikom selektivnog laserskog sinterovanja. in 4. kongres farmaceuta Crne Gore sa međunarodnim učešćem, 11-14. maj 2023. Budva, Bečići, Crna Gora, Zbornik sažetaka
Farmaceutska komora Crne Gore., PP-12, 104-105.
https://hdl.handle.net/21.15107/rcub_farfar_5335

Adamov I, Medarević Đ, Pešić N, Ivković B, Kočović D, Grujić B, Ibrić S. Formulacija i karakterizacija oralno-disperzibilnih tableta desloratadina dobijenih 3D tehnikom selektivnog laserskog sinterovanja. in 4. kongres farmaceuta Crne Gore sa međunarodnim učešćem, 11-14. maj 2023. Budva, Bečići, Crna Gora, Zbornik sažetaka. 2023;PP-12:104-105.
https://hdl.handle.net/21.15107/rcub_farfar_5335 .

Adamov, Ivana, Medarević, Đorđe, Pešić, Nikola, Ivković, Branka, Kočović, David, Grujić, Branka, Ibrić, Svetlana, "Formulacija i karakterizacija oralno-disperzibilnih tableta desloratadina dobijenih 3D tehnikom selektivnog laserskog sinterovanja" in 4. kongres farmaceuta Crne Gore sa međunarodnim učešćem, 11-14. maj 2023. Budva, Bečići, Crna Gora, Zbornik sažetaka, PP-12 (2023):104-105,
https://hdl.handle.net/21.15107/rcub_farfar_5335 .

TY  - CONF
AU  - Pešić, Nikola
AU  - Krkobabić, Mirjana
AU  - Adamov, Ivana
AU  - Ivković, Branka
AU  - Ibrić, Svetlana
AU  - Mirković, Dušica
AU  - Medarević, Đorđe
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5069
AB  - The adjustment of the dose according to the individual
needs of the patient is a unique advantage of 3D printing
technology, which is of particular importance for the
pediatric and geriatric population, due to the diverse needs
and characteristics of these groups of patients (Kotta et al.,
2018).
Selective laser sintering (SLS) is one of the newest 3D
printing techniques that uses powder materials, where the
powder particles are connected under the influence of laser
beams. The main disadvantage of SLS 3D printing is the
high process temperature, which can lead to the
degradation of active substances. On the other hand, this
technique has many advantages, such as high resolution,
the possibility of powder recycling and the absence of pre-
processing (Fina et al., 2018; Thakkar et al., 2021).
PB  - Macedonian Pharmaceutical Association
PB  - Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy
C3  - Macedonian Pharmaceutical Bulletin
T1  - 3D printing of carvedilol oral dosage forms using selective laser sintering technique
VL  - 69
IS  - Suppl 1
SP  - 169
EP  - 170
DO  - 10.33320/maced.pharm.bull.2023.69.03.083
ER  - 

@conference{
author = "Pešić, Nikola and Krkobabić, Mirjana and Adamov, Ivana and Ivković, Branka and Ibrić, Svetlana and Mirković, Dušica and Medarević, Đorđe",
year = "2023",
abstract = "The adjustment of the dose according to the individual
needs of the patient is a unique advantage of 3D printing
technology, which is of particular importance for the
pediatric and geriatric population, due to the diverse needs
and characteristics of these groups of patients (Kotta et al.,
2018).
Selective laser sintering (SLS) is one of the newest 3D
printing techniques that uses powder materials, where the
powder particles are connected under the influence of laser
beams. The main disadvantage of SLS 3D printing is the
high process temperature, which can lead to the
degradation of active substances. On the other hand, this
technique has many advantages, such as high resolution,
the possibility of powder recycling and the absence of pre-
processing (Fina et al., 2018; Thakkar et al., 2021).",
publisher = "Macedonian Pharmaceutical Association, Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy",
journal = "Macedonian Pharmaceutical Bulletin",
title = "3D printing of carvedilol oral dosage forms using selective laser sintering technique",
volume = "69",
number = "Suppl 1",
pages = "169-170",
doi = "10.33320/maced.pharm.bull.2023.69.03.083"
}

Pešić, N., Krkobabić, M., Adamov, I., Ivković, B., Ibrić, S., Mirković, D.,& Medarević, Đ.. (2023). 3D printing of carvedilol oral dosage forms using selective laser sintering technique. in Macedonian Pharmaceutical Bulletin
Macedonian Pharmaceutical Association., 69(Suppl 1), 169-170.
https://doi.org/10.33320/maced.pharm.bull.2023.69.03.083

Pešić N, Krkobabić M, Adamov I, Ivković B, Ibrić S, Mirković D, Medarević Đ. 3D printing of carvedilol oral dosage forms using selective laser sintering technique. in Macedonian Pharmaceutical Bulletin. 2023;69(Suppl 1):169-170.
doi:10.33320/maced.pharm.bull.2023.69.03.083 .

Pešić, Nikola, Krkobabić, Mirjana, Adamov, Ivana, Ivković, Branka, Ibrić, Svetlana, Mirković, Dušica, Medarević, Đorđe, "3D printing of carvedilol oral dosage forms using selective laser sintering technique" in Macedonian Pharmaceutical Bulletin, 69, no. Suppl 1 (2023):169-170,
https://doi.org/10.33320/maced.pharm.bull.2023.69.03.083 . .

TY  - JOUR
AU  - Turković, Nemanja
AU  - Anđelković, Nastasija
AU  - Obradović, Darija
AU  - Vujić, Zorica
AU  - Ivković, Branka
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5031
AB  - Defining  the  interaction  of  newly  synthesized  compounds  with plasma proteins is an important step in the drug development process. Chromatographic techniques can be successfully used in predicting the biopharmaceutical and pharmacokinetic properties of newly synthesized compounds. The aim of this study is to investigate and isolate the most important molecular properties that affect the interaction of 20 newly synthesized chalcones and commercial compounds (lopinavir, ritonavir, darunavir and ivermectin) with human serum albumin (HSA). The retention behaviour of the selected compounds was tested on a CHIRALPAK®HSA column. A mixture of phosphate buffer (pH 7.0) and isopropanol (80:20 volume ratio) was used as the mobile phase, and the support vector method was used to form the quantitative structure retention relationship (QSRR) model. Based on the obtained values of retention parameters, it was observed that halogenated derivatives show the strongest, and methylated chalcone derivatives the weakest interaction with HSA. By correlating the retention and physicochemical properties of the tested compounds, it was  shown  that  the  structural  (SDSCH)  and  electronic  properties  (MAXQ, EEM_F1) groups have the greatest influence on the retention behaviour and the interaction of the tested compounds with HSA. The obtained QSRR model can be applied in the prediction of the retention characteristics of new, structurally related chalcone derivatives on HSA stationary phase.
AB  - Дефинисање интеракције новосинтетисаних једињења са протеинима плазме је важан корак у процесу развоја лекова. Хроматографске технике се могу успешнo користити у предикцији биофармацеутских и фармакокинетичких особина новосинтетисаних једињења. Циљ овог рада је испитивање и издвајање најзначајнијих молекулских особина које утичу на интеракцију  24  новосинтетисаних халкона и њима сродних једињења са хуманим серумским албумином  (HSA).  Ретенционо понашање одабраних једињења је испитано на  CHIRALPAK®HSA колони. Као мобилна фаза коришћена је смеша фосфатног пуфера (pH 7,0) и изопропанола (запр. однос 80:20). У формирању QSRR модела коришћена је метода вектора подршке. На основу добијених вредности ретенционих параметара уочено је да халогеновани деривати показују најјачу, а метиловани деривати халкона најслабију интеракцију са HSA. Доводећи у корелацију ретенцију ифизичко-хемијска својства испитиваних једињења показало се да структурне  (SDSCH)  и електронске особине  (MAXQ,EEM_F1)  група највише утичу на ретенционо понашање и интеракцију испитиваних једињења са HSA. Добијени QSRR модел се може применити у предикцији ретенционих карактеристика нових, структурно-сродних деривата халконана HSA стационарној фази.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin
T1  - Примена течне хроматографије у дефинисању интеракција новосинтетисаних халкона и сродних супстанци са хуманим серумским албуминима
VL  - 88
IS  - 7-8
SP  - 765
EP  - 776
DO  - 10.2298/JSC221212033T
ER  - 

@article{
author = "Turković, Nemanja and Anđelković, Nastasija and Obradović, Darija and Vujić, Zorica and Ivković, Branka",
year = "2023",
abstract = "Defining  the  interaction  of  newly  synthesized  compounds  with plasma proteins is an important step in the drug development process. Chromatographic techniques can be successfully used in predicting the biopharmaceutical and pharmacokinetic properties of newly synthesized compounds. The aim of this study is to investigate and isolate the most important molecular properties that affect the interaction of 20 newly synthesized chalcones and commercial compounds (lopinavir, ritonavir, darunavir and ivermectin) with human serum albumin (HSA). The retention behaviour of the selected compounds was tested on a CHIRALPAK®HSA column. A mixture of phosphate buffer (pH 7.0) and isopropanol (80:20 volume ratio) was used as the mobile phase, and the support vector method was used to form the quantitative structure retention relationship (QSRR) model. Based on the obtained values of retention parameters, it was observed that halogenated derivatives show the strongest, and methylated chalcone derivatives the weakest interaction with HSA. By correlating the retention and physicochemical properties of the tested compounds, it was  shown  that  the  structural  (SDSCH)  and  electronic  properties  (MAXQ, EEM_F1) groups have the greatest influence on the retention behaviour and the interaction of the tested compounds with HSA. The obtained QSRR model can be applied in the prediction of the retention characteristics of new, structurally related chalcone derivatives on HSA stationary phase., Дефинисање интеракције новосинтетисаних једињења са протеинима плазме је важан корак у процесу развоја лекова. Хроматографске технике се могу успешнo користити у предикцији биофармацеутских и фармакокинетичких особина новосинтетисаних једињења. Циљ овог рада је испитивање и издвајање најзначајнијих молекулских особина које утичу на интеракцију  24  новосинтетисаних халкона и њима сродних једињења са хуманим серумским албумином  (HSA).  Ретенционо понашање одабраних једињења је испитано на  CHIRALPAK®HSA колони. Као мобилна фаза коришћена је смеша фосфатног пуфера (pH 7,0) и изопропанола (запр. однос 80:20). У формирању QSRR модела коришћена је метода вектора подршке. На основу добијених вредности ретенционих параметара уочено је да халогеновани деривати показују најјачу, а метиловани деривати халкона најслабију интеракцију са HSA. Доводећи у корелацију ретенцију ифизичко-хемијска својства испитиваних једињења показало се да структурне  (SDSCH)  и електронске особине  (MAXQ,EEM_F1)  група највише утичу на ретенционо понашање и интеракцију испитиваних једињења са HSA. Добијени QSRR модел се може применити у предикцији ретенционих карактеристика нових, структурно-сродних деривата халконана HSA стационарној фази.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin, Примена течне хроматографије у дефинисању интеракција новосинтетисаних халкона и сродних супстанци са хуманим серумским албуминима",
volume = "88",
number = "7-8",
pages = "765-776",
doi = "10.2298/JSC221212033T"
}

Turković, N., Anđelković, N., Obradović, D., Vujić, Z.,& Ivković, B.. (2023). Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 88(7-8), 765-776.
https://doi.org/10.2298/JSC221212033T

Turković N, Anđelković N, Obradović D, Vujić Z, Ivković B. Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin. in Journal of the Serbian Chemical Society. 2023;88(7-8):765-776.
doi:10.2298/JSC221212033T .

Turković, Nemanja, Anđelković, Nastasija, Obradović, Darija, Vujić, Zorica, Ivković, Branka, "Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin" in Journal of the Serbian Chemical Society, 88, no. 7-8 (2023):765-776,
https://doi.org/10.2298/JSC221212033T . .

TY  - JOUR
AU  - Ivković, Branka
AU  - Crevar, Milkica
AU  - Cvetanović, Anka
AU  - Ubavkić, Katarina
AU  - Marković, Bojan
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4435
AB  - Corticosteroids are anti-inflammatory and immunosuppressant drugs. Topical corticosteroids formulations (ointments, creams, gels) are used in the treatment of different types of dermatitis and urticaria. Considering their therapeutic and whitening effects, they are frequently used for counterfeiting of cosmetic products. Corticosteroids can cause different local and systemic side effects. HPLC method is often chosen for their analysis, because it is selective, sensitive, precise, simple and fast. The aim of this study was optimization and validation of RP-HPLC method with UV detection for determination of trace levels of corticosteroids in ambiphilic creams. This method is used for qualitative and quantitative analysis of evaluated corticosteroids. Mometasone furoate, hydrocortisone acetate, fluocinonide, fluocinolone acetonide, betamethasone, betamethasone dipropionate and triamcinolone acetonide were evaluated. Separation was performed on Inertsil® ODS-3V 250 × 4.6 mm, 5 μm chromatographic column. Mobile phase was mixture of acetonitrile and water 50:50 (v/v) with gradient elution and flow rate 1 mL min-1. Column temperature was held on 40 °C and UV detection was performed at 240 nm. Selectivity, linearity, accuracy, precision and limit of quantification (LOQ) were evaluated. Method is selective because ambiphilic cream base peaks and corticosteroids peaks were not overlapping. Linearity was confirmed since correlation coefficient was 1 for all compounds. Accuracy and precision were evaluated for hydrocortisone acetate and betamethasone dipropionate. Determined Recovery values were in range of 70-130%. Both RSD values (21.46% and 9.59%) were lower than 30%. Method is highly sensitive since LOQ concentrations were in ng mL-1 range. All evaluated parameters of validation were in accordance with regulatory requirements. Validated RP-HPLC method can be used for qualitative and quantitative analysis of selected corticosteroids in ambiphilic creams.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream
VL  - 35
IS  - 1
SP  - 46
EP  - 51
DO  - 10.1556/1326.2021.00998
ER  - 

@article{
author = "Ivković, Branka and Crevar, Milkica and Cvetanović, Anka and Ubavkić, Katarina and Marković, Bojan",
year = "2023",
abstract = "Corticosteroids are anti-inflammatory and immunosuppressant drugs. Topical corticosteroids formulations (ointments, creams, gels) are used in the treatment of different types of dermatitis and urticaria. Considering their therapeutic and whitening effects, they are frequently used for counterfeiting of cosmetic products. Corticosteroids can cause different local and systemic side effects. HPLC method is often chosen for their analysis, because it is selective, sensitive, precise, simple and fast. The aim of this study was optimization and validation of RP-HPLC method with UV detection for determination of trace levels of corticosteroids in ambiphilic creams. This method is used for qualitative and quantitative analysis of evaluated corticosteroids. Mometasone furoate, hydrocortisone acetate, fluocinonide, fluocinolone acetonide, betamethasone, betamethasone dipropionate and triamcinolone acetonide were evaluated. Separation was performed on Inertsil® ODS-3V 250 × 4.6 mm, 5 μm chromatographic column. Mobile phase was mixture of acetonitrile and water 50:50 (v/v) with gradient elution and flow rate 1 mL min-1. Column temperature was held on 40 °C and UV detection was performed at 240 nm. Selectivity, linearity, accuracy, precision and limit of quantification (LOQ) were evaluated. Method is selective because ambiphilic cream base peaks and corticosteroids peaks were not overlapping. Linearity was confirmed since correlation coefficient was 1 for all compounds. Accuracy and precision were evaluated for hydrocortisone acetate and betamethasone dipropionate. Determined Recovery values were in range of 70-130%. Both RSD values (21.46% and 9.59%) were lower than 30%. Method is highly sensitive since LOQ concentrations were in ng mL-1 range. All evaluated parameters of validation were in accordance with regulatory requirements. Validated RP-HPLC method can be used for qualitative and quantitative analysis of selected corticosteroids in ambiphilic creams.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream",
volume = "35",
number = "1",
pages = "46-51",
doi = "10.1556/1326.2021.00998"
}

Ivković, B., Crevar, M., Cvetanović, A., Ubavkić, K.,& Marković, B.. (2023). Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream. in Acta Chromatographica
Akademiai Kiado ZRt.., 35(1), 46-51.
https://doi.org/10.1556/1326.2021.00998

Ivković B, Crevar M, Cvetanović A, Ubavkić K, Marković B. Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream. in Acta Chromatographica. 2023;35(1):46-51.
doi:10.1556/1326.2021.00998 .

Ivković, Branka, Crevar, Milkica, Cvetanović, Anka, Ubavkić, Katarina, Marković, Bojan, "Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream" in Acta Chromatographica, 35, no. 1 (2023):46-51,
https://doi.org/10.1556/1326.2021.00998 . .

TY  - CONF
AU  - Vasiljević, Ivana
AU  - Pasik, Paulina
AU  - Turković, Erna
AU  - Ivković, Branka
AU  - Hejduk, Arkadiusz
AU  - Lulek, Janina
AU  - Parojčić, Jelena
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5072
AB  - Direct compression represents a favorable tablet
manufacturing method. However, obtaining satisfactory
mechanical properties of the compacts and drug dissolution
remains a challenge in formulation development,
particularly in the case of challenging model drugs.
Rivaroxaban is classified as a class II model drug
according to the Biopharmaceutical Classification System
and exhibits prominent cohesiveness and low aqueous
solubility (Choi et al., 2022). The aim of this work was to
evaluate the influence of different directly compressible
fillers/diluents on selected compact properties (namely,
tensile strength, friability, and disintegration) and the
dissolution of rivaroxaban from the prepared compacts.
PB  - Macedonian Pharmaceutical Association
PB  - Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy
C3  - Macedonian Pharmaceutical Bulletin
T1  - The influence of directly compressible fillers/diluents on selected compact properties and drug dissolution: a case study of rivaroxaban
VL  - 69
IS  - Suppl 1
SP  - 289
EP  - 290
DO  - 10.33320/maced.pharm.bull.2023.69.03.140
ER  - 

@conference{
author = "Vasiljević, Ivana and Pasik, Paulina and Turković, Erna and Ivković, Branka and Hejduk, Arkadiusz and Lulek, Janina and Parojčić, Jelena",
year = "2023",
abstract = "Direct compression represents a favorable tablet
manufacturing method. However, obtaining satisfactory
mechanical properties of the compacts and drug dissolution
remains a challenge in formulation development,
particularly in the case of challenging model drugs.
Rivaroxaban is classified as a class II model drug
according to the Biopharmaceutical Classification System
and exhibits prominent cohesiveness and low aqueous
solubility (Choi et al., 2022). The aim of this work was to
evaluate the influence of different directly compressible
fillers/diluents on selected compact properties (namely,
tensile strength, friability, and disintegration) and the
dissolution of rivaroxaban from the prepared compacts.",
publisher = "Macedonian Pharmaceutical Association, Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy",
journal = "Macedonian Pharmaceutical Bulletin",
title = "The influence of directly compressible fillers/diluents on selected compact properties and drug dissolution: a case study of rivaroxaban",
volume = "69",
number = "Suppl 1",
pages = "289-290",
doi = "10.33320/maced.pharm.bull.2023.69.03.140"
}

Vasiljević, I., Pasik, P., Turković, E., Ivković, B., Hejduk, A., Lulek, J.,& Parojčić, J.. (2023). The influence of directly compressible fillers/diluents on selected compact properties and drug dissolution: a case study of rivaroxaban. in Macedonian Pharmaceutical Bulletin
Macedonian Pharmaceutical Association., 69(Suppl 1), 289-290.
https://doi.org/10.33320/maced.pharm.bull.2023.69.03.140

Vasiljević I, Pasik P, Turković E, Ivković B, Hejduk A, Lulek J, Parojčić J. The influence of directly compressible fillers/diluents on selected compact properties and drug dissolution: a case study of rivaroxaban. in Macedonian Pharmaceutical Bulletin. 2023;69(Suppl 1):289-290.
doi:10.33320/maced.pharm.bull.2023.69.03.140 .

Vasiljević, Ivana, Pasik, Paulina, Turković, Erna, Ivković, Branka, Hejduk, Arkadiusz, Lulek, Janina, Parojčić, Jelena, "The influence of directly compressible fillers/diluents on selected compact properties and drug dissolution: a case study of rivaroxaban" in Macedonian Pharmaceutical Bulletin, 69, no. Suppl 1 (2023):289-290,
https://doi.org/10.33320/maced.pharm.bull.2023.69.03.140 . .

TY  - CONF
AU  - Selaković, Milan
AU  - Aleksić, Mara
AU  - Ivković, Branka
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4603
AB  - Ivermectin (IVM) is a drug from the group of anthelmintics used in veterinary and
human medicine. Recently, it has been used in the treatment of some malignant diseases, as
well as viral infections caused by Zika virus, HIV-1, SARS-CoV-2, which has increased the
interest in this medicine (1). Electrochemical characterization of IVM was done with the aim
of better understanding the redox behavior of the molecule, as well as to predict potential
transformations during interactions with other electroactive biomolecules. Electrochemical
behavior was examined by cyclic (CV), differential pulse (DPV) and square wave
voltammetry (SWV) using a glassy carbon electrode (GCE). The effect of pH was examined in
the pH range 2–10. The results confirmed that IVM is electroactive in the entire study area.
IVM shows the main oxidation peak at a potential of about 1.0 V, which is most intense in a
neutral environment, and an additional (weakly expressed) peak, due to oxidation of the
reduced drug form. In voltammograms, there is also a peak of low intensity, which originates
from the reduction of the previously oxidized form of the drug. Based on the shape of the
voltammogram, it is concluded that all these processes are irreversible. The analysis of the
influence of the rate of change of potential (pH 4.6 and 7.0) is also responsible for the
adsorption of the active component on the electrode. The presented results indicate the
advantage of applying electrochemical methods in drug analysis due to low cost, high speed
and ease of execution.
AB  - Ivermektin (IVM) je lek iz grupe antihelmintik koji se primenjuje u veterinarskoj i
humanoj medicini. U novije vreme našao je primenu i kao lek u terapiji nekih malignih
oboljenja, kao i virusnih infekcija prouzrokovanih virusom Zika, HIV-1, SARS-CoV-2 , čime je
ponovo poraslo interesovanje za ovaj lek (1). Elektrohemijska karakterizacija IVM je rađena
sa ciljem boljeg razumevanja redoks ponašanja samog molekula, kao i za predviđanje
potencijalnih transformacija tokom interakcija sa drugim elektroaktivnim lekovima ili
biomolekulima. Elektrohemijsko ponašanje IVM-a ispitivano je cikličnom (CV),
diferencijalnom pulsnom (DPV) i voltametrijom pravougaonih talasa (SWV) korišćenjem
elektrode od staklastog ugljenika (GCE). Uticaj pH na oksidaciju i redukciju IVM ispitan je u
opsegu pH 2–10. Rezultati su potvrdili da je IVM elektroaktivan u celoj ispitivanoj oblasti.
IVM pokazuje glavni oksidacioni pik na potencijalu oko 1,0 V koji je najintenzivniji u
neutralnoj sredini i dodatni (slabo izražen) pik koji je posledica oksidacije redukovanog
oblika leka . U voltamogramima IVM-a javlja se i pik slabog intenziteta koji potiče od
redukcije prethodno oksidovane forme leka. Na osnovu oblika voltamograma zaključuje se
da su svi navedeni procesi ireverzibilni. Analizom uticaja brzine promene potencijala (pH 4,6
i 7,0) određena je priroda redoks procesa: oksidacija IVM-a je difuziono kontrolisan proces,
dok je pored difuzije za redukciju IVM-a odgovorna i adsorpcija aktivne komponente na
elektrodi. Pored svog fundamentalnog značaja, prikazani rezultati ukazuju na prednost
primene elektrohemijskih metoda u analizi lekova zbog niske cene, velike brzine i
jednostavnosti izvođenja.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Ivermectin electrochemical behavoiur at glassy carbon electrode
T1  - Elektrohemijsko ponašanje ivermektina na elektrodi od staklastog ugljenika
VL  - 72
IS  - 4 suplement
SP  - S544
EP  - S545
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4603
ER  - 

@conference{
author = "Selaković, Milan and Aleksić, Mara and Ivković, Branka",
year = "2022",
abstract = "Ivermectin (IVM) is a drug from the group of anthelmintics used in veterinary and
human medicine. Recently, it has been used in the treatment of some malignant diseases, as
well as viral infections caused by Zika virus, HIV-1, SARS-CoV-2, which has increased the
interest in this medicine (1). Electrochemical characterization of IVM was done with the aim
of better understanding the redox behavior of the molecule, as well as to predict potential
transformations during interactions with other electroactive biomolecules. Electrochemical
behavior was examined by cyclic (CV), differential pulse (DPV) and square wave
voltammetry (SWV) using a glassy carbon electrode (GCE). The effect of pH was examined in
the pH range 2–10. The results confirmed that IVM is electroactive in the entire study area.
IVM shows the main oxidation peak at a potential of about 1.0 V, which is most intense in a
neutral environment, and an additional (weakly expressed) peak, due to oxidation of the
reduced drug form. In voltammograms, there is also a peak of low intensity, which originates
from the reduction of the previously oxidized form of the drug. Based on the shape of the
voltammogram, it is concluded that all these processes are irreversible. The analysis of the
influence of the rate of change of potential (pH 4.6 and 7.0) is also responsible for the
adsorption of the active component on the electrode. The presented results indicate the
advantage of applying electrochemical methods in drug analysis due to low cost, high speed
and ease of execution., Ivermektin (IVM) je lek iz grupe antihelmintik koji se primenjuje u veterinarskoj i
humanoj medicini. U novije vreme našao je primenu i kao lek u terapiji nekih malignih
oboljenja, kao i virusnih infekcija prouzrokovanih virusom Zika, HIV-1, SARS-CoV-2 , čime je
ponovo poraslo interesovanje za ovaj lek (1). Elektrohemijska karakterizacija IVM je rađena
sa ciljem boljeg razumevanja redoks ponašanja samog molekula, kao i za predviđanje
potencijalnih transformacija tokom interakcija sa drugim elektroaktivnim lekovima ili
biomolekulima. Elektrohemijsko ponašanje IVM-a ispitivano je cikličnom (CV),
diferencijalnom pulsnom (DPV) i voltametrijom pravougaonih talasa (SWV) korišćenjem
elektrode od staklastog ugljenika (GCE). Uticaj pH na oksidaciju i redukciju IVM ispitan je u
opsegu pH 2–10. Rezultati su potvrdili da je IVM elektroaktivan u celoj ispitivanoj oblasti.
IVM pokazuje glavni oksidacioni pik na potencijalu oko 1,0 V koji je najintenzivniji u
neutralnoj sredini i dodatni (slabo izražen) pik koji je posledica oksidacije redukovanog
oblika leka . U voltamogramima IVM-a javlja se i pik slabog intenziteta koji potiče od
redukcije prethodno oksidovane forme leka. Na osnovu oblika voltamograma zaključuje se
da su svi navedeni procesi ireverzibilni. Analizom uticaja brzine promene potencijala (pH 4,6
i 7,0) određena je priroda redoks procesa: oksidacija IVM-a je difuziono kontrolisan proces,
dok je pored difuzije za redukciju IVM-a odgovorna i adsorpcija aktivne komponente na
elektrodi. Pored svog fundamentalnog značaja, prikazani rezultati ukazuju na prednost
primene elektrohemijskih metoda u analizi lekova zbog niske cene, velike brzine i
jednostavnosti izvođenja.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Ivermectin electrochemical behavoiur at glassy carbon electrode, Elektrohemijsko ponašanje ivermektina na elektrodi od staklastog ugljenika",
volume = "72",
number = "4 suplement",
pages = "S544-S545",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4603"
}

Selaković, M., Aleksić, M.,& Ivković, B.. (2022). Ivermectin electrochemical behavoiur at glassy carbon electrode. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S544-S545.
https://hdl.handle.net/21.15107/rcub_farfar_4603

Selaković M, Aleksić M, Ivković B. Ivermectin electrochemical behavoiur at glassy carbon electrode. in Arhiv za farmaciju. 2022;72(4 suplement):S544-S545.
https://hdl.handle.net/21.15107/rcub_farfar_4603 .

Selaković, Milan, Aleksić, Mara, Ivković, Branka, "Ivermectin electrochemical behavoiur at glassy carbon electrode" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S544-S545,
https://hdl.handle.net/21.15107/rcub_farfar_4603 .

TY  - CONF
AU  - Turković, Nemanja
AU  - Tasić, Milica
AU  - Kotur-Stevuljević, Jelena
AU  - Vujić, Zorica
AU  - Ivković, Branka
AU  - Ivković, Aleksandar
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4491
AB  - The discovery of HIV and the study of molecular mechanisms crucial for the virus
replication cycle have led to the identification of important protein structures - potential
targets of drug action in AIDS therapy. One of the most significant discoveries is HIV-1
protease (PR), an enzyme that plays a key role in the HIV replication cycle (1). This study
aimed to test and demonstrate the interactions of newly synthesized chalcones (1,3-diaryl-2-
propen-1-one) as well as three commercial drugs (lopinavir, ritonavir and darunavir) in the
active site of HIV-1 protease using in sillico methods. and that the results obtained correlate
with the results of in vitro tests on the enzyme itself. The twenty structurally similar
chalcone derivatives were synthesized and their physico-chemical characterization was
performed. Docking calculations were performed using the Autodock Wine program in the
3D structure of the enzime catalytic site (pdb code: 6B36). The inhibition of enzyme activity
was monitored by fluorimetric method (2). The obtained results revealed that all compounds
showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity
with an IC 50 values of 0.001 μM which is comparable with commercial product Darunavir.
The results obtained indicate that the synthesized compounds can be classified as potential
anti-HIV-1 protease inhibitors. Further research is focused on testing the ADMET properties
of the synthesized compounds as well as the synthesis of their analogues for which in silico
tests have shown satisfactory results.
AB  - Otkrić e HIV-a i istraživanje molekularnih mehanizama ključnih za ciklus replikacije
virusa dovelo je do identifikacije važnih proteinskih struktura - potencijalnih ciljnih mesta
dejstva lekova u terapiji AIDS-a. Jedno od najznačajnijih otkrića je HIV-1 proteaza (PR),
enzim koji ima ključnu ulogu u ciklusu replikacije HIV-a (1). Ova studija imala je za cilj da
primenom in sillico metoda ispita i prikaže interakcije novosintetisanih halkona (1,3-diaril-2-
propen-1-ona) kao i tri komercijalna leka (lopinavira, ritonavira i darunavira) u aktivnom
mestu HIV-1 proteaze i da dobijene rezultate koreliše sa rezultatima in vitro testova na
samom enzimu. Sintetisano je dvadeset strukturno sličnih derivata halkona i izvršena
njihova fizičko-hemijska karakterizacija. Docking studije izvedene su u programu Autodock
Vine u 3D strukturi enzimskog katalitičkog mesta (pdb kod: 6B36). Inhibicija enzimske
aktivnosti određena je primenom fluorimetrijske metode (2). Dobijeni rezultati ukazuju da
svih 20 jedinjenja ispoljava anti-HIV-1 proteaznu aktivnost. Jedinjenje HNT1 je pokazalo
najveć u inhibitornu aktivnost sa vrednostima IC50 od 0,001 μM što je uporedivo sa
komercijalnim proizvodom darunavirom. Dobijeni rezultati ukazuju da se sitetisana
jedinjenja mogu klasifikovati kao potencijalni anti-HIV-1 proteazni inhibitori. Dalje
istraživanje je usmereno na ispitivanju ADMET osobina sintetisanih jedinjenja kao i sintezi
njihovih analoga za koje su in silico ispitivanja pokazala zadovoljavajuće rezultate.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Chalcones are potential inhibitors of HIV-1 protease
T1  - Halkoni potencijalni inhibitori HIV‐1 proteaze
VL  - 72
IS  - 4 suplement
SP  - S186
EP  - S187
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4491
ER  - 

@conference{
author = "Turković, Nemanja and Tasić, Milica and Kotur-Stevuljević, Jelena and Vujić, Zorica and Ivković, Branka and Ivković, Aleksandar",
year = "2022",
abstract = "The discovery of HIV and the study of molecular mechanisms crucial for the virus
replication cycle have led to the identification of important protein structures - potential
targets of drug action in AIDS therapy. One of the most significant discoveries is HIV-1
protease (PR), an enzyme that plays a key role in the HIV replication cycle (1). This study
aimed to test and demonstrate the interactions of newly synthesized chalcones (1,3-diaryl-2-
propen-1-one) as well as three commercial drugs (lopinavir, ritonavir and darunavir) in the
active site of HIV-1 protease using in sillico methods. and that the results obtained correlate
with the results of in vitro tests on the enzyme itself. The twenty structurally similar
chalcone derivatives were synthesized and their physico-chemical characterization was
performed. Docking calculations were performed using the Autodock Wine program in the
3D structure of the enzime catalytic site (pdb code: 6B36). The inhibition of enzyme activity
was monitored by fluorimetric method (2). The obtained results revealed that all compounds
showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity
with an IC 50 values of 0.001 μM which is comparable with commercial product Darunavir.
The results obtained indicate that the synthesized compounds can be classified as potential
anti-HIV-1 protease inhibitors. Further research is focused on testing the ADMET properties
of the synthesized compounds as well as the synthesis of their analogues for which in silico
tests have shown satisfactory results., Otkrić e HIV-a i istraživanje molekularnih mehanizama ključnih za ciklus replikacije
virusa dovelo je do identifikacije važnih proteinskih struktura - potencijalnih ciljnih mesta
dejstva lekova u terapiji AIDS-a. Jedno od najznačajnijih otkrića je HIV-1 proteaza (PR),
enzim koji ima ključnu ulogu u ciklusu replikacije HIV-a (1). Ova studija imala je za cilj da
primenom in sillico metoda ispita i prikaže interakcije novosintetisanih halkona (1,3-diaril-2-
propen-1-ona) kao i tri komercijalna leka (lopinavira, ritonavira i darunavira) u aktivnom
mestu HIV-1 proteaze i da dobijene rezultate koreliše sa rezultatima in vitro testova na
samom enzimu. Sintetisano je dvadeset strukturno sličnih derivata halkona i izvršena
njihova fizičko-hemijska karakterizacija. Docking studije izvedene su u programu Autodock
Vine u 3D strukturi enzimskog katalitičkog mesta (pdb kod: 6B36). Inhibicija enzimske
aktivnosti određena je primenom fluorimetrijske metode (2). Dobijeni rezultati ukazuju da
svih 20 jedinjenja ispoljava anti-HIV-1 proteaznu aktivnost. Jedinjenje HNT1 je pokazalo
najveć u inhibitornu aktivnost sa vrednostima IC50 od 0,001 μM što je uporedivo sa
komercijalnim proizvodom darunavirom. Dobijeni rezultati ukazuju da se sitetisana
jedinjenja mogu klasifikovati kao potencijalni anti-HIV-1 proteazni inhibitori. Dalje
istraživanje je usmereno na ispitivanju ADMET osobina sintetisanih jedinjenja kao i sintezi
njihovih analoga za koje su in silico ispitivanja pokazala zadovoljavajuće rezultate.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Chalcones are potential inhibitors of HIV-1 protease, Halkoni potencijalni inhibitori HIV‐1 proteaze",
volume = "72",
number = "4 suplement",
pages = "S186-S187",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4491"
}

Turković, N., Tasić, M., Kotur-Stevuljević, J., Vujić, Z., Ivković, B.,& Ivković, A.. (2022). Chalcones are potential inhibitors of HIV-1 protease. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S186-S187.
https://hdl.handle.net/21.15107/rcub_farfar_4491

Turković N, Tasić M, Kotur-Stevuljević J, Vujić Z, Ivković B, Ivković A. Chalcones are potential inhibitors of HIV-1 protease. in Arhiv za farmaciju. 2022;72(4 suplement):S186-S187.
https://hdl.handle.net/21.15107/rcub_farfar_4491 .

Turković, Nemanja, Tasić, Milica, Kotur-Stevuljević, Jelena, Vujić, Zorica, Ivković, Branka, Ivković, Aleksandar, "Chalcones are potential inhibitors of HIV-1 protease" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S186-S187,
https://hdl.handle.net/21.15107/rcub_farfar_4491 .

TY  - CONF
AU  - Pešić, Nikola
AU  - Krkobabić, Mirjana
AU  - Adamov, Ivana
AU  - Ibrić, Svetlana
AU  - Ivković, Branka
AU  - Medarević, Đorđe
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4749
AB  - 1. INTRODUCTION
When it comes to pharmacy, 3D printing has
gained immense popularity in recent years due
to its revolutionary use in printing drugs tailored
to individual patient needs [1,2]. Selective laser
sintering (SLS) is an industrial 3D printing
technique which uses a powder bed to build up
the 3D object thanks to a laser which binds the
powder particles together. Advantages of SLS
technique include the fact that it is a solvent-free
process and offers relatively fast production.
Until today, a limited number of studies
investigating the production of drug dosage
forms using SLS have been reported [2,3].
2. MATERIALS AND METHODS
2.1. Materials
Carvedilol (CRV) was used as a model
substance in this study and it was donated by
Hemofarm (Vršac, Serbia). The following
excipients used to obtain 3D printing tablets:
polyvinyl alcohol (PVA, Merck), mannitol
(Parteck® M, Merck), Ludipress®
(coprocessed excipient consisting of 93%
lactose monohydrate, 3.5% crospovidone
(Kollidon® CL) and 3.5% povidone K30
(Kollidon® 30), BASF), talc (Merck) and
candurin (Candurin® Gold Sheen, Merck).
2.2. Preparation of formulations
The compositions of the formulations are
shown in Table 1.
Table 1. Composition of the formulations
Material Formulation 1 Formulation 2
CRV 10% 10%
PVA 55% 55%
Parteck® M 30% /
Ludipress® / 30%
Talc 2% 2%
Candurin®
Gold Sheen 3% 3%
Powder for 3D printing was obtained by mixing
all the components of the formulation and
sifting through a sieve with a diameter of 180
μm.
2.3. 3D printing of oral dosage forms
A cylindrical 3D models of the printed tablets
(8.00 mm diameter and 2.00 mm thickness)
were designed with Autodesk Fusion 360
software version 2.0.8809 (Autodesk Inc, San
Rafael, CA, USA), exported as a
stereolithography file (.stl) and printed with
Sintratec Kit 3D printer (Sintratec AG,
Switzerland). The printing parameters were
controlled using Sintratec 3D printer software.
After a series of variations in temperature and
laser speed, the optimal values of these
parameters used in the 3D printing process were
established and shown in Table 2.
Table 2. SLS 3D printing process parameters
Surface
Temperature
( ◦C)
Chamber
Temperature
( ◦C)
Laser
speed
(mm/s)
Hatch
space
80 ºC 70 ºC 60 250 μm
2.4. Mechanical properties of 3D tablets
Tablets (n = 10) were weighed on a Sartorius BP
210 D analytical balance (Sartorius, Goettingen,
Germany) and measured (diameter and
thickness) using a digital caliper (Vogel,
Kevelaer, Germany).
2.5. Powder X-ray diffraction analysis
(PXRD)
PXRD analysis was performed to assess
whether the laser induced amorphization of any
of the compounds, especially amorphization of
poorly soluble CRV. Samples were collected
using a Philips PW-1050 (Philips, The
Netherlands) diffractometer, operated at 40 kV
and 30 mA, using Ni-filtered Cu Kα radiation.
2.6. Dissolution and Drug Release Analysis
Dissolution testing was performed under nonsink
conditions using mini paddle apparatus
(Erweka DT 600, Germany) with a paddle
rotation speed of 50 rpm for 8 h, in 100 ml of
phosphate buffer (pH 6.8). The amount of
dissolved CRV was determined by HPLC
method using Dionex Ultimate 3000 (Thermo
Scientific, USA) HPLC system.
3. RESULTS AND DISCUSSION
3.1. 3D printing process
It was shown that SLS printer was able to
fabricate 3D tablets with CRV, as well as that
success of the printing process depended on the
used printing parameters.
3.2. Mechanical properties of 3D tablets
The dimensions of the obtained 3D tablets were
in accordance with the defined values of the
created 3D models (F1: 8.10 ± 0.08 mm
diameter and 2.10 ± 0.13 mm thickness, F2:
8.13 ± 0.09 mm diameter and 2.10 ± 0.12 mm
thickness). Significant variations in tablet
weight between formulations were not observed
(m1=0.146 ± 0.04; m2=0.136 ± 0.03).
3.3. Powder X-ray diffraction analysis
(PXRD)
Figure 1. The X-ray powder diffraction of F1
and F2.
3.4. Dissolution and Drug Release Analysis
Figure 2. Dissolution profiles of 3D printing
tablets
4. CONCLUSION
SLA represents a new chapter in 3D printing of
solid oral dosage forms and in individualized
therapy in particular. By adjusting the
formulation and process parameters, it was
possible to produce SLS tablets with coamorphous
CRV and PVA as a main polymer.
Complete drug release was achieved under non
sink conditions after 8 hours in phosphate
buffer. The tailoring of drug release might be
achieved by varying formulation factors as well
as process parameters, although it could be
governed by the composition of the whole
formulation.
PB  - Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo
C3  - 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts
T1  - Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique
SP  - 210
EP  - 211
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4749
ER  - 

@conference{
author = "Pešić, Nikola and Krkobabić, Mirjana and Adamov, Ivana and Ibrić, Svetlana and Ivković, Branka and Medarević, Đorđe",
year = "2022",
abstract = "1. INTRODUCTION
When it comes to pharmacy, 3D printing has
gained immense popularity in recent years due
to its revolutionary use in printing drugs tailored
to individual patient needs [1,2]. Selective laser
sintering (SLS) is an industrial 3D printing
technique which uses a powder bed to build up
the 3D object thanks to a laser which binds the
powder particles together. Advantages of SLS
technique include the fact that it is a solvent-free
process and offers relatively fast production.
Until today, a limited number of studies
investigating the production of drug dosage
forms using SLS have been reported [2,3].
2. MATERIALS AND METHODS
2.1. Materials
Carvedilol (CRV) was used as a model
substance in this study and it was donated by
Hemofarm (Vršac, Serbia). The following
excipients used to obtain 3D printing tablets:
polyvinyl alcohol (PVA, Merck), mannitol
(Parteck® M, Merck), Ludipress®
(coprocessed excipient consisting of 93%
lactose monohydrate, 3.5% crospovidone
(Kollidon® CL) and 3.5% povidone K30
(Kollidon® 30), BASF), talc (Merck) and
candurin (Candurin® Gold Sheen, Merck).
2.2. Preparation of formulations
The compositions of the formulations are
shown in Table 1.
Table 1. Composition of the formulations
Material Formulation 1 Formulation 2
CRV 10% 10%
PVA 55% 55%
Parteck® M 30% /
Ludipress® / 30%
Talc 2% 2%
Candurin®
Gold Sheen 3% 3%
Powder for 3D printing was obtained by mixing
all the components of the formulation and
sifting through a sieve with a diameter of 180
μm.
2.3. 3D printing of oral dosage forms
A cylindrical 3D models of the printed tablets
(8.00 mm diameter and 2.00 mm thickness)
were designed with Autodesk Fusion 360
software version 2.0.8809 (Autodesk Inc, San
Rafael, CA, USA), exported as a
stereolithography file (.stl) and printed with
Sintratec Kit 3D printer (Sintratec AG,
Switzerland). The printing parameters were
controlled using Sintratec 3D printer software.
After a series of variations in temperature and
laser speed, the optimal values of these
parameters used in the 3D printing process were
established and shown in Table 2.
Table 2. SLS 3D printing process parameters
Surface
Temperature
( ◦C)
Chamber
Temperature
( ◦C)
Laser
speed
(mm/s)
Hatch
space
80 ºC 70 ºC 60 250 μm
2.4. Mechanical properties of 3D tablets
Tablets (n = 10) were weighed on a Sartorius BP
210 D analytical balance (Sartorius, Goettingen,
Germany) and measured (diameter and
thickness) using a digital caliper (Vogel,
Kevelaer, Germany).
2.5. Powder X-ray diffraction analysis
(PXRD)
PXRD analysis was performed to assess
whether the laser induced amorphization of any
of the compounds, especially amorphization of
poorly soluble CRV. Samples were collected
using a Philips PW-1050 (Philips, The
Netherlands) diffractometer, operated at 40 kV
and 30 mA, using Ni-filtered Cu Kα radiation.
2.6. Dissolution and Drug Release Analysis
Dissolution testing was performed under nonsink
conditions using mini paddle apparatus
(Erweka DT 600, Germany) with a paddle
rotation speed of 50 rpm for 8 h, in 100 ml of
phosphate buffer (pH 6.8). The amount of
dissolved CRV was determined by HPLC
method using Dionex Ultimate 3000 (Thermo
Scientific, USA) HPLC system.
3. RESULTS AND DISCUSSION
3.1. 3D printing process
It was shown that SLS printer was able to
fabricate 3D tablets with CRV, as well as that
success of the printing process depended on the
used printing parameters.
3.2. Mechanical properties of 3D tablets
The dimensions of the obtained 3D tablets were
in accordance with the defined values of the
created 3D models (F1: 8.10 ± 0.08 mm
diameter and 2.10 ± 0.13 mm thickness, F2:
8.13 ± 0.09 mm diameter and 2.10 ± 0.12 mm
thickness). Significant variations in tablet
weight between formulations were not observed
(m1=0.146 ± 0.04; m2=0.136 ± 0.03).
3.3. Powder X-ray diffraction analysis
(PXRD)
Figure 1. The X-ray powder diffraction of F1
and F2.
3.4. Dissolution and Drug Release Analysis
Figure 2. Dissolution profiles of 3D printing
tablets
4. CONCLUSION
SLA represents a new chapter in 3D printing of
solid oral dosage forms and in individualized
therapy in particular. By adjusting the
formulation and process parameters, it was
possible to produce SLS tablets with coamorphous
CRV and PVA as a main polymer.
Complete drug release was achieved under non
sink conditions after 8 hours in phosphate
buffer. The tailoring of drug release might be
achieved by varying formulation factors as well
as process parameters, although it could be
governed by the composition of the whole
formulation.",
publisher = "Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo",
journal = "9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts",
title = "Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique",
pages = "210-211",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4749"
}

Pešić, N., Krkobabić, M., Adamov, I., Ibrić, S., Ivković, B.,& Medarević, Đ.. (2022). Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique. in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts
Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo., 210-211.
https://hdl.handle.net/21.15107/rcub_farfar_4749

Pešić N, Krkobabić M, Adamov I, Ibrić S, Ivković B, Medarević Đ. Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique. in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts. 2022;:210-211.
https://hdl.handle.net/21.15107/rcub_farfar_4749 .

Pešić, Nikola, Krkobabić, Mirjana, Adamov, Ivana, Ibrić, Svetlana, Ivković, Branka, Medarević, Đorđe, "Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique" in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts (2022):210-211,
https://hdl.handle.net/21.15107/rcub_farfar_4749 .

TY  - CONF
AU  - Adamov, Ivana
AU  - Tenić, Milica
AU  - Pešić, Nikola
AU  - Medarević, Đorđe
AU  - Ivković, Branka
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4573
AB  - In recent years, introduction of modern technologies, such as 3D printing, has
opened a new chapter and caused a paradigm shift from manufacturing of large-scale to
small batches of medicines tailored accordingly to the specific needs of patients (1). The aim
of this study was to formulate and fabricate two-layered tablets using digital light processing
(DLP) technique, which utilizes light irradiation to create solid objects from photoreactive
liquid resin in a layer-by-layer manner. Hydrochlorothiazide (HHT, 5%,w/w) and warfarin
sodium (VRN, 5%,w/w) were selected as model drugs, commonly used together in the
treatment of cardiovascular diseases. 3D printing process was initiated with 0.10% of
photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and poly(ethylene
glycol) 400, 1:1, with the addition of water (10%,w/w). 3D tablets, with each of the active
substances in a separate layer, 8.00 mm in diameter and 1.50 mm thick, as well as combined
two-layered tablets with HHT and VRN in individual layers, were successfully printed with
Wanhao D8 printer. Dissolution test results showed immediate, but incomplete release of
VRN (81.47 ± 1.47%, after 45 min) from individual layers, while the release of HHT was
prolonged and complete (98.17 ± 3.11%, after 8 h). Significantly slower and incomplete
release of VRN and HHT from combined tablets was observed. The absence of interactions
and the presence of a layered structure were confirmed. DLP technique has a potential to
provide fast fabrication of combined tablets, while further optimization of formulation
factors is necessary in order to achieve complete drug release.
AB  - Poslednjih godina, uvođenjem savremenih tehnologija, poput 3D štampe, otvorilo se
novo poglavlje u načinu proizvodnje lekova i uslovilo razvoj fundamentalnih promena, pri
čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama
lekova prilagođenih specifičnim potrebama pacijenata (1). Cilj ovog istraživanja bio je da se
formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP) koja
omogućava dobijanje objekata mehanizmom nanošenja materijala “sloj po sloj” iz tečne
fotopolimerizacione smole pod uticajem svetlosti. Hidrohlortiazid (HHT, 5%, m/m) i
varfarin-natrijum (VRN, 5%, m/m) odabrani su kao model lekovite supstance, koje se obično
primenjuju zajedno u lečenju kardiovaskularnih bolesti. Proces 3D štampanja sproveden je u
prisustvu 0,10% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen
glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. 3D tablete, sa svakom
od aktivnih supstanci u posebnom sloju, prečnika 8,00 mm i debljine 1,50 mm, kao i
kombinovane dvoslojne tablete sa HHT i VRN u pojedinačnim slojevima, uspešno su
odštampane u Wanhao D8 štampaču. Prilikom ispitivanja brzine rastvaranja lekovite
supstance iz pojedinačnih slojeva, došlo je do trenutnog (81,47 ± 1,47% nakon 45 min), ali
nepotpunog oslobađanja VRN, dok je HHT u potpunosti oslobođen, prateći kinetiku
produženog oslobađanja (98,17 ± 3,11%, nakon 8 h). Zapaženo je znatno sporije i nepotpuno
oslobađanje VRN i HHT iz kombinovanih dvoslojnih tableta, nakon 8 h. Potvrđeno je
odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika ima potencijal da obezbedi
brzu izradu kombinovanih tableta, pri čemu je neophodna dalja optimizacija formulacionih
faktora u cilju postizanja potpunog oslobađanja lekovite supstance.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets
T1  - Primena fotopolimerizacione tehnike 3D štampe lekova u izradi dvoslojnih tableta
VL  - 72
IS  - 4 suplement
SP  - S410
EP  - S411
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4573
ER  - 

@conference{
author = "Adamov, Ivana and Tenić, Milica and Pešić, Nikola and Medarević, Đorđe and Ivković, Branka and Ibrić, Svetlana",
year = "2022",
abstract = "In recent years, introduction of modern technologies, such as 3D printing, has
opened a new chapter and caused a paradigm shift from manufacturing of large-scale to
small batches of medicines tailored accordingly to the specific needs of patients (1). The aim
of this study was to formulate and fabricate two-layered tablets using digital light processing
(DLP) technique, which utilizes light irradiation to create solid objects from photoreactive
liquid resin in a layer-by-layer manner. Hydrochlorothiazide (HHT, 5%,w/w) and warfarin
sodium (VRN, 5%,w/w) were selected as model drugs, commonly used together in the
treatment of cardiovascular diseases. 3D printing process was initiated with 0.10% of
photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and poly(ethylene
glycol) 400, 1:1, with the addition of water (10%,w/w). 3D tablets, with each of the active
substances in a separate layer, 8.00 mm in diameter and 1.50 mm thick, as well as combined
two-layered tablets with HHT and VRN in individual layers, were successfully printed with
Wanhao D8 printer. Dissolution test results showed immediate, but incomplete release of
VRN (81.47 ± 1.47%, after 45 min) from individual layers, while the release of HHT was
prolonged and complete (98.17 ± 3.11%, after 8 h). Significantly slower and incomplete
release of VRN and HHT from combined tablets was observed. The absence of interactions
and the presence of a layered structure were confirmed. DLP technique has a potential to
provide fast fabrication of combined tablets, while further optimization of formulation
factors is necessary in order to achieve complete drug release., Poslednjih godina, uvođenjem savremenih tehnologija, poput 3D štampe, otvorilo se
novo poglavlje u načinu proizvodnje lekova i uslovilo razvoj fundamentalnih promena, pri
čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama
lekova prilagođenih specifičnim potrebama pacijenata (1). Cilj ovog istraživanja bio je da se
formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP) koja
omogućava dobijanje objekata mehanizmom nanošenja materijala “sloj po sloj” iz tečne
fotopolimerizacione smole pod uticajem svetlosti. Hidrohlortiazid (HHT, 5%, m/m) i
varfarin-natrijum (VRN, 5%, m/m) odabrani su kao model lekovite supstance, koje se obično
primenjuju zajedno u lečenju kardiovaskularnih bolesti. Proces 3D štampanja sproveden je u
prisustvu 0,10% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen
glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. 3D tablete, sa svakom
od aktivnih supstanci u posebnom sloju, prečnika 8,00 mm i debljine 1,50 mm, kao i
kombinovane dvoslojne tablete sa HHT i VRN u pojedinačnim slojevima, uspešno su
odštampane u Wanhao D8 štampaču. Prilikom ispitivanja brzine rastvaranja lekovite
supstance iz pojedinačnih slojeva, došlo je do trenutnog (81,47 ± 1,47% nakon 45 min), ali
nepotpunog oslobađanja VRN, dok je HHT u potpunosti oslobođen, prateći kinetiku
produženog oslobađanja (98,17 ± 3,11%, nakon 8 h). Zapaženo je znatno sporije i nepotpuno
oslobađanje VRN i HHT iz kombinovanih dvoslojnih tableta, nakon 8 h. Potvrđeno je
odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika ima potencijal da obezbedi
brzu izradu kombinovanih tableta, pri čemu je neophodna dalja optimizacija formulacionih
faktora u cilju postizanja potpunog oslobađanja lekovite supstance.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets, Primena fotopolimerizacione tehnike 3D štampe lekova u izradi dvoslojnih tableta",
volume = "72",
number = "4 suplement",
pages = "S410-S411",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4573"
}

Adamov, I., Tenić, M., Pešić, N., Medarević, Đ., Ivković, B.,& Ibrić, S.. (2022). Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S410-S411.
https://hdl.handle.net/21.15107/rcub_farfar_4573

Adamov I, Tenić M, Pešić N, Medarević Đ, Ivković B, Ibrić S. Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets. in Arhiv za farmaciju. 2022;72(4 suplement):S410-S411.
https://hdl.handle.net/21.15107/rcub_farfar_4573 .

Adamov, Ivana, Tenić, Milica, Pešić, Nikola, Medarević, Đorđe, Ivković, Branka, Ibrić, Svetlana, "Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S410-S411,
https://hdl.handle.net/21.15107/rcub_farfar_4573 .

TY  - JOUR
AU  - Adamov, Ivana
AU  - Medarević, Đorđe
AU  - Ivković, Branka
AU  - Ivković, Aleksandar
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4411
AB  - Ever since 3D printing was introduced to the field of pharmacy, it has caused a paradigm
shift from the manufacturing of large-scale to small batches of medicines tailored accordingly to
the specific needs of patients. This study aimed to formulate and fabricate two-layered 3D tablets
using the digital light processing (DLP) technique. Hydrochlorothiazide (HHT,5%,w/w) and
warfarin sodium (WS,5%,w/w) were selected as model drugs. The printing process was initiated
with 0.1% of photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and
poly(ethylene glycol) 400, 1:1, with the addition of water (10%,w/w). Single-layered tablets of
8.00 mm diameter and 1.50 mm thickness, containing HHT and WS respectively, were
successfully printed, as well as combined two-layered 3D tablets, with each of the active
substances in separate layers. Dissolution tests of single-layered tablets showed immediate, but
incomplete release of WS (81.47±1.47%, after 45min), and prolonged and complete release of
HHT (98.17±3.11%, after 8h), while significantly slower and incomplete release of both drugs
from the combined two-layered 3D tablets was observed. The absence of drug-polymer
interaction and presence of a layered cross-sectional tablet structure were confirmed. DLP
technique enables simple and rapid fabrication of combined two-layered 3D tablets, while further
optimization of formulation factors is necessary to achieve complete drug release.
AB  - Uvođenje tehnologije 3D štampe u oblasti farmacije uslovilo je razvoj fundamentalnih promena, pri čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama lekova prilagođenih prema specifičnim potrebama pacijenata. Cilj istraživanja bio je da se formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP). Hidrohlortiazid (HHT, 5%, m/m) i varfarin-natrijum (WS, 5%, m/m) odabrani su kao model lekovite supstance. Proces štampanja sproveden je u prisustvu 0,1% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. Jednoslojne 3D tablete prečnika 8,00 mm i debljine 1,50 mm, koje sadrže HHT, odnosno WS, kao i kombinovane dvoslojne 3D tablete, sa svakom od aktivnih supstanci u posebnom sloju, uspešno su odštampane. Prilikom ispitivanja brzine rastvaranja lekovite supstance iz jednoslojnih tableta, došlo je do trenutnog (81,47±1,47%, nakon 45 min), ali nepotpunog oslobađanja WS, i produženog i potpunog oslobađanja HHT (98,17±3,11%, nakon 8 h), dok je iz kombinovanih tableta zapaženo znatno sporije i nepotpuno oslobađanje obe lekovite supstance. Potvrđeno je odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika pruža mogućnost jednostavne i brze izrade kombinovanih tableta, pri čemu je dalja optimizacija formulacionih faktora neophodna u cilju postizanja potpunog oslobađanja lekovite supstance.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill
T1  - 3D tehnika digitalne obrade svetlosti (DLP) primenjena u izradi dvoslojnih tableta: koncept kombinovane polipilule
VL  - 72
IS  - 6
SP  - 674
EP  - 688
DO  - 10.5937/arhfarm72-40365
ER  - 

@article{
author = "Adamov, Ivana and Medarević, Đorđe and Ivković, Branka and Ivković, Aleksandar and Ibrić, Svetlana",
year = "2022",
abstract = "Ever since 3D printing was introduced to the field of pharmacy, it has caused a paradigm
shift from the manufacturing of large-scale to small batches of medicines tailored accordingly to
the specific needs of patients. This study aimed to formulate and fabricate two-layered 3D tablets
using the digital light processing (DLP) technique. Hydrochlorothiazide (HHT,5%,w/w) and
warfarin sodium (WS,5%,w/w) were selected as model drugs. The printing process was initiated
with 0.1% of photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and
poly(ethylene glycol) 400, 1:1, with the addition of water (10%,w/w). Single-layered tablets of
8.00 mm diameter and 1.50 mm thickness, containing HHT and WS respectively, were
successfully printed, as well as combined two-layered 3D tablets, with each of the active
substances in separate layers. Dissolution tests of single-layered tablets showed immediate, but
incomplete release of WS (81.47±1.47%, after 45min), and prolonged and complete release of
HHT (98.17±3.11%, after 8h), while significantly slower and incomplete release of both drugs
from the combined two-layered 3D tablets was observed. The absence of drug-polymer
interaction and presence of a layered cross-sectional tablet structure were confirmed. DLP
technique enables simple and rapid fabrication of combined two-layered 3D tablets, while further
optimization of formulation factors is necessary to achieve complete drug release., Uvođenje tehnologije 3D štampe u oblasti farmacije uslovilo je razvoj fundamentalnih promena, pri čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama lekova prilagođenih prema specifičnim potrebama pacijenata. Cilj istraživanja bio je da se formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP). Hidrohlortiazid (HHT, 5%, m/m) i varfarin-natrijum (WS, 5%, m/m) odabrani su kao model lekovite supstance. Proces štampanja sproveden je u prisustvu 0,1% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. Jednoslojne 3D tablete prečnika 8,00 mm i debljine 1,50 mm, koje sadrže HHT, odnosno WS, kao i kombinovane dvoslojne 3D tablete, sa svakom od aktivnih supstanci u posebnom sloju, uspešno su odštampane. Prilikom ispitivanja brzine rastvaranja lekovite supstance iz jednoslojnih tableta, došlo je do trenutnog (81,47±1,47%, nakon 45 min), ali nepotpunog oslobađanja WS, i produženog i potpunog oslobađanja HHT (98,17±3,11%, nakon 8 h), dok je iz kombinovanih tableta zapaženo znatno sporije i nepotpuno oslobađanje obe lekovite supstance. Potvrđeno je odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika pruža mogućnost jednostavne i brze izrade kombinovanih tableta, pri čemu je dalja optimizacija formulacionih faktora neophodna u cilju postizanja potpunog oslobađanja lekovite supstance.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill, 3D tehnika digitalne obrade svetlosti (DLP) primenjena u izradi dvoslojnih tableta: koncept kombinovane polipilule",
volume = "72",
number = "6",
pages = "674-688",
doi = "10.5937/arhfarm72-40365"
}

Adamov, I., Medarević, Đ., Ivković, B., Ivković, A.,& Ibrić, S.. (2022). Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(6), 674-688.
https://doi.org/10.5937/arhfarm72-40365

Adamov I, Medarević Đ, Ivković B, Ivković A, Ibrić S. Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill. in Arhiv za farmaciju. 2022;72(6):674-688.
doi:10.5937/arhfarm72-40365 .

Adamov, Ivana, Medarević, Đorđe, Ivković, Branka, Ivković, Aleksandar, Ibrić, Svetlana, "Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill" in Arhiv za farmaciju, 72, no. 6 (2022):674-688,
https://doi.org/10.5937/arhfarm72-40365 . .

TY  - JOUR
AU  - Adamov, Ivana
AU  - Stanojević, Gordana
AU  - Medarević, Đorđe
AU  - Ivković, Branka
AU  - Kočović, David
AU  - Mirković, Dušica
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4275
AB  - The introduction of three-dimensional (3D) printing in the pharmaceutical field has made great strides towards innovations in the way drugs are designed and manufactured. In this study, digital light processing (DLP) technique was used to fabricate oral dosage forms of different shapes with zolpidem tartrate (ZT), incorporated within its therapeutic range. Formulation factors, such as poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 (PEG 400) ratio, as well as water content, were varied in combination with the surface area/volume (SA/V) ratio to achieve immediate drug release. Hypromellose (HPMC) was used as a stabilizing agent of photoreactive suspensions in an attempt to prevent drug sedimentation and subsequent variations in drug content uniformity. Oral dosage forms with doses in the range from 0.15 mg to 6.37 mg, showing very rapid and rapid drug dissolution, were successfully fabricated, confirming the potential of this technique in drug manufacturing with the ability to provide flexible dose adjustments and desirable release profiles by varying formulation factors and geometry of 3D models. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and scanning electron microscopy (SEM) showed that ZT remained in a crystalline form within printed dosage forms and no interactions were found between ZT and polymers.
PB  - Elsevier
T2  - International journal of pharmaceutics
T1  - Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique
VL  - 624
DO  - 10.1016/j.ijpharm.2022.122046
ER  - 

@article{
author = "Adamov, Ivana and Stanojević, Gordana and Medarević, Đorđe and Ivković, Branka and Kočović, David and Mirković, Dušica and Ibrić, Svetlana",
year = "2022",
abstract = "The introduction of three-dimensional (3D) printing in the pharmaceutical field has made great strides towards innovations in the way drugs are designed and manufactured. In this study, digital light processing (DLP) technique was used to fabricate oral dosage forms of different shapes with zolpidem tartrate (ZT), incorporated within its therapeutic range. Formulation factors, such as poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 (PEG 400) ratio, as well as water content, were varied in combination with the surface area/volume (SA/V) ratio to achieve immediate drug release. Hypromellose (HPMC) was used as a stabilizing agent of photoreactive suspensions in an attempt to prevent drug sedimentation and subsequent variations in drug content uniformity. Oral dosage forms with doses in the range from 0.15 mg to 6.37 mg, showing very rapid and rapid drug dissolution, were successfully fabricated, confirming the potential of this technique in drug manufacturing with the ability to provide flexible dose adjustments and desirable release profiles by varying formulation factors and geometry of 3D models. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and scanning electron microscopy (SEM) showed that ZT remained in a crystalline form within printed dosage forms and no interactions were found between ZT and polymers.",
publisher = "Elsevier",
journal = "International journal of pharmaceutics",
title = "Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique",
volume = "624",
doi = "10.1016/j.ijpharm.2022.122046"
}

Adamov, I., Stanojević, G., Medarević, Đ., Ivković, B., Kočović, D., Mirković, D.,& Ibrić, S.. (2022). Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique. in International journal of pharmaceutics
Elsevier., 624.
https://doi.org/10.1016/j.ijpharm.2022.122046

Adamov I, Stanojević G, Medarević Đ, Ivković B, Kočović D, Mirković D, Ibrić S. Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique. in International journal of pharmaceutics. 2022;624.
doi:10.1016/j.ijpharm.2022.122046 .

Adamov, Ivana, Stanojević, Gordana, Medarević, Đorđe, Ivković, Branka, Kočović, David, Mirković, Dušica, Ibrić, Svetlana, "Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique" in International journal of pharmaceutics, 624 (2022),
https://doi.org/10.1016/j.ijpharm.2022.122046 . .

TY  - JOUR
AU  - Osmanović Omerdić, Ehlimana
AU  - Alagić-Džambić, Larisa
AU  - Krstić, Marko
AU  - Pašić-Kulenović, Maja
AU  - Medarević, Đorđe
AU  - Ivković, Branka
AU  - Vasiljević, Dragana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4085
AB  - Formulation of solid dispersions (SDs), in which the drug substance is dissolved or dispersed inside a polymer matrix, is one of the modern approaches to increase the solubility and dissolution rate of poorly soluble active pharmaceutical ingredients (APIs), such as clopidogrel. In the form of a free base, clopidogrel is unstable under increased both high moisture and temperature, so it is most often used as its salt form, clopidogrel hydrogen sulfate (CHS).The aim of this study was the formulation, characterization, and long-term stability investigation of CHS solid dispersions, prepared with four different hydrophilic polymers (poloxamer 407, macrogol 6000, povidone, copovidone) in five API/polymer ratios (1:1, 1:2, 1:3, 1:5, 1:9). SDs were prepared by the solvent evaporation method, employing ethanol (96% v/v) as a solvent. Initial results of the in vitro dissolution test showed an increase in the amount of dissolved CHS from all prepared SD samples compared to pure CHS, corresponding physical mixtures (PMs), and commercial tablets. SDs, prepared with poloxamer 407, macrogol 6000, and copovidone, at CHS/polymer ratios 1:5 and 1:9, notably increased the amount of dissolved CHS (> 80%, after 60 min), thus they were selected for further characterization. To assess the SDs long-term stability, in vitro dissolution studies, clopidogrel content determination, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) were performed initially and after 12 months of long-term stability studies under controlled conditions (25°C, 60% RH) meeting the ICH guideline Q1A (R2) requirements. The clopidogrel content in the selected samples was very similar at the beginning (96.13% to 99.93%) and at the end (95.98% to 99.86%) of the conducted test. DSC curves and FT-IR spectra of all SD samples after 12 months of stability study, showed the absence of CHS crystallization, which is an indication of good stability. However, the in vitro dissolution test showed a considerable reduction in CHS released from SDs with macrogol 6000. The amount of dissolved CHS from SDs with macrogol 6000 was initially 94.02% and 92.01%, and after 12 months of stability study, only 65.13% and 49.62%. In contrast, the amount of dissolved CHS from SDs prepared with poloxamer 407 and copovidone was very similar after 12 months of the stability study compared to the initial values. Results obtained indicated the great importance of the in vitro dissolution test in determining the long-term stability and quality of SDs.
PB  - NLM (Medline)
T2  - PloS one
T1  - Long-term stability of clopidogrel solid dispersions-Importance of in vitro dissolution test
VL  - 17
IS  - 4
DO  - 10.1371/journal.pone.0266237
ER  - 

@article{
author = "Osmanović Omerdić, Ehlimana and Alagić-Džambić, Larisa and Krstić, Marko and Pašić-Kulenović, Maja and Medarević, Đorđe and Ivković, Branka and Vasiljević, Dragana",
year = "2022",
abstract = "Formulation of solid dispersions (SDs), in which the drug substance is dissolved or dispersed inside a polymer matrix, is one of the modern approaches to increase the solubility and dissolution rate of poorly soluble active pharmaceutical ingredients (APIs), such as clopidogrel. In the form of a free base, clopidogrel is unstable under increased both high moisture and temperature, so it is most often used as its salt form, clopidogrel hydrogen sulfate (CHS).The aim of this study was the formulation, characterization, and long-term stability investigation of CHS solid dispersions, prepared with four different hydrophilic polymers (poloxamer 407, macrogol 6000, povidone, copovidone) in five API/polymer ratios (1:1, 1:2, 1:3, 1:5, 1:9). SDs were prepared by the solvent evaporation method, employing ethanol (96% v/v) as a solvent. Initial results of the in vitro dissolution test showed an increase in the amount of dissolved CHS from all prepared SD samples compared to pure CHS, corresponding physical mixtures (PMs), and commercial tablets. SDs, prepared with poloxamer 407, macrogol 6000, and copovidone, at CHS/polymer ratios 1:5 and 1:9, notably increased the amount of dissolved CHS (> 80%, after 60 min), thus they were selected for further characterization. To assess the SDs long-term stability, in vitro dissolution studies, clopidogrel content determination, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) were performed initially and after 12 months of long-term stability studies under controlled conditions (25°C, 60% RH) meeting the ICH guideline Q1A (R2) requirements. The clopidogrel content in the selected samples was very similar at the beginning (96.13% to 99.93%) and at the end (95.98% to 99.86%) of the conducted test. DSC curves and FT-IR spectra of all SD samples after 12 months of stability study, showed the absence of CHS crystallization, which is an indication of good stability. However, the in vitro dissolution test showed a considerable reduction in CHS released from SDs with macrogol 6000. The amount of dissolved CHS from SDs with macrogol 6000 was initially 94.02% and 92.01%, and after 12 months of stability study, only 65.13% and 49.62%. In contrast, the amount of dissolved CHS from SDs prepared with poloxamer 407 and copovidone was very similar after 12 months of the stability study compared to the initial values. Results obtained indicated the great importance of the in vitro dissolution test in determining the long-term stability and quality of SDs.",
publisher = "NLM (Medline)",
journal = "PloS one",
title = "Long-term stability of clopidogrel solid dispersions-Importance of in vitro dissolution test",
volume = "17",
number = "4",
doi = "10.1371/journal.pone.0266237"
}

Osmanović Omerdić, E., Alagić-Džambić, L., Krstić, M., Pašić-Kulenović, M., Medarević, Đ., Ivković, B.,& Vasiljević, D.. (2022). Long-term stability of clopidogrel solid dispersions-Importance of in vitro dissolution test. in PloS one
NLM (Medline)., 17(4).
https://doi.org/10.1371/journal.pone.0266237

Osmanović Omerdić E, Alagić-Džambić L, Krstić M, Pašić-Kulenović M, Medarević Đ, Ivković B, Vasiljević D. Long-term stability of clopidogrel solid dispersions-Importance of in vitro dissolution test. in PloS one. 2022;17(4).
doi:10.1371/journal.pone.0266237 .

Osmanović Omerdić, Ehlimana, Alagić-Džambić, Larisa, Krstić, Marko, Pašić-Kulenović, Maja, Medarević, Đorđe, Ivković, Branka, Vasiljević, Dragana, "Long-term stability of clopidogrel solid dispersions-Importance of in vitro dissolution test" in PloS one, 17, no. 4 (2022),
https://doi.org/10.1371/journal.pone.0266237 . .

TY  - CONF
AU  - Ivković, Branka
AU  - Božić, Dragana
AU  - Kotur-Stevuljević, Jelena
AU  - Krajišnik, Danina
AU  - Vujić, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4598
AB  - The global market for antiseptics and disinfectants is growing rapidly, fueled by a
coronavirus pandemic and a possible outbreak of infectious diseases in the future. The
antimicrobial, anti-inflammatory and redox activity of chalcone (1,3-diaryl-2-propen-1-one)
is well documented in the literature. The aim of this study is screening of antimicrobial
activity of chalcones and their saturated derivatives as active pharmaceutical ingredients,
synthesized by Claisen-Schmidt condensation (1). The redox potential of the investigated
compounds was tested in the biological environment using spectrophotometric methods to
determine prooxidant/antioxidant parameters. Within preformulation studies solubility and
compatibility with excipients commonly used in liquid pharmaceutical dosage forms was
performed. All the tested chalcones and their saturated derivatives showed satisfactory
antimicrobial activity, but two saturated chalcones showed the best MIC (0.156 - 1.25 mM)
and were categorized as compounds with strong bacteriostatic activity (2). Solubility of the
chalcons with moderate antimicrobial activity and redox potential was higher than its
minimum bacteriostatic and bactericidal concentration in all the tested solvents (ethanol,
isopropyl alcohol and propylene glycol). Based on the chemical structure and predicted logP
values for saturated chalcones that show stronger antimicrobial activity, better water
solubility is expected. These data could be a starting point for formulations of antiseptics and
disinfectants with lower concentrations of alcohol-based solvents, as the synergism between
saturated chalcone and ethanol and isopropyl alcohol was previously shown. Considering the
lighter color of the saturated chalcone, better aesthetic acceptability of the developed
formulations is expected, since it will not stain the skin and objects during application.
AB  - Globalno tržište antiseptika i dezinfekcionih sredstava ubrzano raste podstaknuto
pandemijom koronavirusa i moguć im širenjem drugih zaraznih bolesti u buduć nosti.
Antimikrobna, antiinflamatorna i redoks aktivnost halkona (1,3-diaril-2-propen-1-ona) je
dobro dokumentovana u literaturi. Cilj ove studije bio je skrining antimikrobne aktivnosti
halkona i njihovih zasić enih derivata kao aktivnih farmaceutskih sastojaka, sintetisanih
Claisen‐Schmidt kondenzacijom (1). Redoks potencijal ispitivanih jedinjenja je ispitan u
biosredini primenom spektrofotometrijskih metoda za određivanje
prooksidantnih/antioksidativnih parametara. Sprovedena su i preformulaciona ispitivanja
rastvorljivosti i kompatibilnosti sa ekscipijensima uobičajeno korišćenim u tečnim
farmaceutskim oblicima. Svi testirani halkoni i njihovi zasić eni derivati su pokazali
zadovoljavajuć u antimikrobnu aktivnost, ali su dva zasić ena halkona pokazala najbolji MIC
(0,156 – 1,25 mM) i kategorisana su kao jedinjenja sa jakom bakteriostatskom aktivnošć u
(2). Rastvorljivost halkona sa umerenom antimikrobnom aktivnošću i redoks potencijalom
bili su viši od njegove minimalne bakteriostatske i baktericidne koncentracije u svim
ispitivanim rastvaračima (etanol, izopropil alkohol i propilenglikol). Na osnovu hemijske
strukture i predviđene logP vrednosti za zasićene halkone koji pokazuju bolju antimikrobnu
aktivnost, očekuje se i bolja rastvorljivost u vodi. Ovi podaci mogli bi da budu polazna osnova
za formulisanje antiseptika i dezinfekcionih sredstava sa nižim koncentracijama rastvarača
na bazi alkohola, uzimajući u obzir da je u prethodnom ispitivanju pokazan sinergizam
između zasićenog halkona i etanola, kao i izopropil alkohola. S obzirom na svetliju boju
zasićenog halkona, očekuje se i bolja estetska prihvatljivost razvijenih formulacija, jer neć e
bojiti kožu i predmete tokom nanošenja.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Chalcone derivatives as potential antiseptics and disinfectants
T1  - Derivati halkona kao potentijalni antiseptici i dezinficijensi
VL  - 72
IS  - 4 suplement
SP  - S532
EP  - S533
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4598
ER  - 

@conference{
author = "Ivković, Branka and Božić, Dragana and Kotur-Stevuljević, Jelena and Krajišnik, Danina and Vujić, Zorica",
year = "2022",
abstract = "The global market for antiseptics and disinfectants is growing rapidly, fueled by a
coronavirus pandemic and a possible outbreak of infectious diseases in the future. The
antimicrobial, anti-inflammatory and redox activity of chalcone (1,3-diaryl-2-propen-1-one)
is well documented in the literature. The aim of this study is screening of antimicrobial
activity of chalcones and their saturated derivatives as active pharmaceutical ingredients,
synthesized by Claisen-Schmidt condensation (1). The redox potential of the investigated
compounds was tested in the biological environment using spectrophotometric methods to
determine prooxidant/antioxidant parameters. Within preformulation studies solubility and
compatibility with excipients commonly used in liquid pharmaceutical dosage forms was
performed. All the tested chalcones and their saturated derivatives showed satisfactory
antimicrobial activity, but two saturated chalcones showed the best MIC (0.156 - 1.25 mM)
and were categorized as compounds with strong bacteriostatic activity (2). Solubility of the
chalcons with moderate antimicrobial activity and redox potential was higher than its
minimum bacteriostatic and bactericidal concentration in all the tested solvents (ethanol,
isopropyl alcohol and propylene glycol). Based on the chemical structure and predicted logP
values for saturated chalcones that show stronger antimicrobial activity, better water
solubility is expected. These data could be a starting point for formulations of antiseptics and
disinfectants with lower concentrations of alcohol-based solvents, as the synergism between
saturated chalcone and ethanol and isopropyl alcohol was previously shown. Considering the
lighter color of the saturated chalcone, better aesthetic acceptability of the developed
formulations is expected, since it will not stain the skin and objects during application., Globalno tržište antiseptika i dezinfekcionih sredstava ubrzano raste podstaknuto
pandemijom koronavirusa i moguć im širenjem drugih zaraznih bolesti u buduć nosti.
Antimikrobna, antiinflamatorna i redoks aktivnost halkona (1,3-diaril-2-propen-1-ona) je
dobro dokumentovana u literaturi. Cilj ove studije bio je skrining antimikrobne aktivnosti
halkona i njihovih zasić enih derivata kao aktivnih farmaceutskih sastojaka, sintetisanih
Claisen‐Schmidt kondenzacijom (1). Redoks potencijal ispitivanih jedinjenja je ispitan u
biosredini primenom spektrofotometrijskih metoda za određivanje
prooksidantnih/antioksidativnih parametara. Sprovedena su i preformulaciona ispitivanja
rastvorljivosti i kompatibilnosti sa ekscipijensima uobičajeno korišćenim u tečnim
farmaceutskim oblicima. Svi testirani halkoni i njihovi zasić eni derivati su pokazali
zadovoljavajuć u antimikrobnu aktivnost, ali su dva zasić ena halkona pokazala najbolji MIC
(0,156 – 1,25 mM) i kategorisana su kao jedinjenja sa jakom bakteriostatskom aktivnošć u
(2). Rastvorljivost halkona sa umerenom antimikrobnom aktivnošću i redoks potencijalom
bili su viši od njegove minimalne bakteriostatske i baktericidne koncentracije u svim
ispitivanim rastvaračima (etanol, izopropil alkohol i propilenglikol). Na osnovu hemijske
strukture i predviđene logP vrednosti za zasićene halkone koji pokazuju bolju antimikrobnu
aktivnost, očekuje se i bolja rastvorljivost u vodi. Ovi podaci mogli bi da budu polazna osnova
za formulisanje antiseptika i dezinfekcionih sredstava sa nižim koncentracijama rastvarača
na bazi alkohola, uzimajući u obzir da je u prethodnom ispitivanju pokazan sinergizam
između zasićenog halkona i etanola, kao i izopropil alkohola. S obzirom na svetliju boju
zasićenog halkona, očekuje se i bolja estetska prihvatljivost razvijenih formulacija, jer neć e
bojiti kožu i predmete tokom nanošenja.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Chalcone derivatives as potential antiseptics and disinfectants, Derivati halkona kao potentijalni antiseptici i dezinficijensi",
volume = "72",
number = "4 suplement",
pages = "S532-S533",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4598"
}

Ivković, B., Božić, D., Kotur-Stevuljević, J., Krajišnik, D.,& Vujić, Z.. (2022). Chalcone derivatives as potential antiseptics and disinfectants. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S532-S533.
https://hdl.handle.net/21.15107/rcub_farfar_4598

Ivković B, Božić D, Kotur-Stevuljević J, Krajišnik D, Vujić Z. Chalcone derivatives as potential antiseptics and disinfectants. in Arhiv za farmaciju. 2022;72(4 suplement):S532-S533.
https://hdl.handle.net/21.15107/rcub_farfar_4598 .

Ivković, Branka, Božić, Dragana, Kotur-Stevuljević, Jelena, Krajišnik, Danina, Vujić, Zorica, "Chalcone derivatives as potential antiseptics and disinfectants" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S532-S533,
https://hdl.handle.net/21.15107/rcub_farfar_4598 .

TY  - CONF
AU  - Zabelaj, Davor
AU  - Ivković, Branka
AU  - Čudina, Olivera
AU  - Brborić, Jasmina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4602
AB  - Flunixin is a non-steroidal anti-inflammatory drug, as well as an analgesic that has an
antipyretic effect. In veterinary medicine, it is used as salt flunixin meglumine. Flunixin
shows strong inhibition of the cyclooxygenase system involved in the development of
inflammation (1). The decrease in the production of certain inflammatory mediators explains
its analgesic, antipyretic and anti-inflammatory properties. A large number of methods have
been developed for the separation of flunixin meglumine and structurally related
compounds in pharmaceutical preparations, such as: thin layer chromatography, UV/VIS
spectroscopy, high pressure liquid chromatography and gas chromatography. The objective
of this work is to develop, optimize and validate a method for separating flunixin meglumine
and structurally related substances, in solution for injection. Optimal conditions were
achieved on a Agilent Zorbax Eclipse Plus C18 column (150×4.6 mm, 5 μm). The mobile
phase is a mixture of 0.1% (v/v) formic acid in water and methanol in a ratio of 40:60 (v/v).
The flow rate is 1.0 mL/min, the injection volume is 20 μL, the detection wavelength is 270
nm and the column temperature is 25°C. The following parameters were examined:
selectivity, linearity, precision, accuracy, detection limit, quantification limit, robustness and
stability of the solution (2). All these parameters were in line with the criteria for accepting
the results. Thereafter, the method was applied to determine the content of flunixin
meglumine and its impurities in the solution for injection, and the result was also in
accordance with the criteria for accepting the results.
AB  - Fluniksin je nesteroidni antiinflamatorni lek, kao i analgetik koji ima antipiretički
efekat. U veterinarskoj medicini se koristi u obliku soli fluniksin-meglumina. Fluniksin
pokazuje snažnu inhibiciju enzima ciklooksigenaze koji je uključen u nastanak inflamacije
(1). Smanjenjem produkcije određenih medijatora inflamacije objašnjavaju se njegova
analgetička, antipiretička i antiinflamatorna svojstva. Razvijen je veliki broj metoda za
odvajanje fluniksin meglumina i strukturno srodnih jedinjenja u farmaceutskim preparatima,
kao što su: tankoslojna hromatografija, UV/VIS spektroskopija, visokoefikasna tečna
hromatografija, gasna hromatografija. Cilj ovoga rada je razvoj, optimizacija i validacija
metode za razdvajanje i određivanje fluniksin-meglumina i strukturno sličnih jedinjenja, u
rastvoru za injekciju. Optimalni uslovi postignuti su na koloni Agilent Zorbax Eclipse Plus
C18 (150×4,6 mm, 5 μm). Mobilnu fazu činila je smeša 0,1% v/v rastvora mravlje kiseline u
vodi i metanola u odnosu 40:60 v/v. Protok mobilne faze je 1,0 mL/min, volumen injiciranja
20 μL, talasna dužina detekcije 270 nm i temperatura kolone 25°C. Ispitivani su sledeći
parametri: selektivnost, linearnost, preciznost, tačnost, limit detekcije, limit kvantifikacije,
robustnost i stabilnost rastvora (2). Dobijene vrednosti za ispitivane parametre su u skladu
sa kriterijumima prihvatljivosti. Validirana metoda je primenjena za određivanje sadržaja
fluniksin-meglumina i njegovih nečistoća u rastvoru za injekcije. Dobijeni rezultati
zadovoljavali su zahteve specifikacije.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use
T1  - Razvoj i validacija metode tečne hromatografije visokih performansi za određivanje fluniksin‐meglumina i njegovih nečistoća u preparatima za veterinarsku upotrebu
VL  - 72
IS  - 4 suplement
SP  - S540
EP  - S541
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4602
ER  - 

@conference{
author = "Zabelaj, Davor and Ivković, Branka and Čudina, Olivera and Brborić, Jasmina",
year = "2022",
abstract = "Flunixin is a non-steroidal anti-inflammatory drug, as well as an analgesic that has an
antipyretic effect. In veterinary medicine, it is used as salt flunixin meglumine. Flunixin
shows strong inhibition of the cyclooxygenase system involved in the development of
inflammation (1). The decrease in the production of certain inflammatory mediators explains
its analgesic, antipyretic and anti-inflammatory properties. A large number of methods have
been developed for the separation of flunixin meglumine and structurally related
compounds in pharmaceutical preparations, such as: thin layer chromatography, UV/VIS
spectroscopy, high pressure liquid chromatography and gas chromatography. The objective
of this work is to develop, optimize and validate a method for separating flunixin meglumine
and structurally related substances, in solution for injection. Optimal conditions were
achieved on a Agilent Zorbax Eclipse Plus C18 column (150×4.6 mm, 5 μm). The mobile
phase is a mixture of 0.1% (v/v) formic acid in water and methanol in a ratio of 40:60 (v/v).
The flow rate is 1.0 mL/min, the injection volume is 20 μL, the detection wavelength is 270
nm and the column temperature is 25°C. The following parameters were examined:
selectivity, linearity, precision, accuracy, detection limit, quantification limit, robustness and
stability of the solution (2). All these parameters were in line with the criteria for accepting
the results. Thereafter, the method was applied to determine the content of flunixin
meglumine and its impurities in the solution for injection, and the result was also in
accordance with the criteria for accepting the results., Fluniksin je nesteroidni antiinflamatorni lek, kao i analgetik koji ima antipiretički
efekat. U veterinarskoj medicini se koristi u obliku soli fluniksin-meglumina. Fluniksin
pokazuje snažnu inhibiciju enzima ciklooksigenaze koji je uključen u nastanak inflamacije
(1). Smanjenjem produkcije određenih medijatora inflamacije objašnjavaju se njegova
analgetička, antipiretička i antiinflamatorna svojstva. Razvijen je veliki broj metoda za
odvajanje fluniksin meglumina i strukturno srodnih jedinjenja u farmaceutskim preparatima,
kao što su: tankoslojna hromatografija, UV/VIS spektroskopija, visokoefikasna tečna
hromatografija, gasna hromatografija. Cilj ovoga rada je razvoj, optimizacija i validacija
metode za razdvajanje i određivanje fluniksin-meglumina i strukturno sličnih jedinjenja, u
rastvoru za injekciju. Optimalni uslovi postignuti su na koloni Agilent Zorbax Eclipse Plus
C18 (150×4,6 mm, 5 μm). Mobilnu fazu činila je smeša 0,1% v/v rastvora mravlje kiseline u
vodi i metanola u odnosu 40:60 v/v. Protok mobilne faze je 1,0 mL/min, volumen injiciranja
20 μL, talasna dužina detekcije 270 nm i temperatura kolone 25°C. Ispitivani su sledeći
parametri: selektivnost, linearnost, preciznost, tačnost, limit detekcije, limit kvantifikacije,
robustnost i stabilnost rastvora (2). Dobijene vrednosti za ispitivane parametre su u skladu
sa kriterijumima prihvatljivosti. Validirana metoda je primenjena za određivanje sadržaja
fluniksin-meglumina i njegovih nečistoća u rastvoru za injekcije. Dobijeni rezultati
zadovoljavali su zahteve specifikacije.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use, Razvoj i validacija metode tečne hromatografije visokih performansi za određivanje fluniksin‐meglumina i njegovih nečistoća u preparatima za veterinarsku upotrebu",
volume = "72",
number = "4 suplement",
pages = "S540-S541",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4602"
}

Zabelaj, D., Ivković, B., Čudina, O.,& Brborić, J.. (2022). Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S540-S541.
https://hdl.handle.net/21.15107/rcub_farfar_4602

Zabelaj D, Ivković B, Čudina O, Brborić J. Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use. in Arhiv za farmaciju. 2022;72(4 suplement):S540-S541.
https://hdl.handle.net/21.15107/rcub_farfar_4602 .

Zabelaj, Davor, Ivković, Branka, Čudina, Olivera, Brborić, Jasmina, "Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S540-S541,
https://hdl.handle.net/21.15107/rcub_farfar_4602 .

TY  - JOUR
AU  - Ivković, Branka
AU  - Opačić, Dragan
AU  - Džudović, Boris
AU  - Crevar, Milkica
AU  - Gojković-Bukarica, Ljiljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4306
AB  - It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with-Cl or –F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PVT. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects.
AB  - Dobro je poznato da prisustvo različitih hemijskih grupa u molekulima leka utiče na
njegova farmakološka svojstva. Cilj našeg istraživanja je ispitati da li novosintetisani derivati
propafenona, s promenama u benzilnoj grupi, imaju drugačiji efekat na aritmiju u odnosu na
propafenon. 5OCl-PF i 5OF-PF su derivati propafenona sa -Cl ili –F supstituentom na orto
položaju benzilnog dela. Za proveru njihovog antiaritmičnog efekta koristili smo in vivo model
na pacovima sa aritmijom izazvanom akonitinom. 5OCl-PF je ubrzao pojavu
supraventrikularnih prevremenih otkucaja (SVPB) i smrt više nego akonitin. Sve životinje
lečene sa 5OCl-PF razvile su ventrikularne prevremene otkucaje (VPBS i VPBB) i
paroksizmalnu ventrikularnu tahikardiju (PVT). 5OF-PF je imao negativan hronotropni efekat i
potencirao atrijalnu ekscitabilnost (više SVPB). Pozitivno je uticao na pojavu i vreme početka
supraventrikularne tahikardije, VPBS i PVT. Na osnovu dobijenih rezultata se može zaključiti
da novosintetisani derivati propafenona nemaju bolji antiaritmijski efekat od polaznog
jedinjenja. U budućnosti, istraživanje će biti usmereno ka sintezi hemijski drugačijih derivata i
ispitivanju njihovog antiaritmijskog efekta.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Antiarrhythmic effects of newly developed propafenone derivatives
T1  - Antiaritmički efekti novosintetisanih derivata
propafenona
VL  - 72
IS  - 4
SP  - 392
EP  - 412
DO  - 10.5937/arhfarm72-37114
ER  - 

@article{
author = "Ivković, Branka and Opačić, Dragan and Džudović, Boris and Crevar, Milkica and Gojković-Bukarica, Ljiljana",
year = "2022",
abstract = "It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with-Cl or –F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PVT. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects., Dobro je poznato da prisustvo različitih hemijskih grupa u molekulima leka utiče na
njegova farmakološka svojstva. Cilj našeg istraživanja je ispitati da li novosintetisani derivati
propafenona, s promenama u benzilnoj grupi, imaju drugačiji efekat na aritmiju u odnosu na
propafenon. 5OCl-PF i 5OF-PF su derivati propafenona sa -Cl ili –F supstituentom na orto
položaju benzilnog dela. Za proveru njihovog antiaritmičnog efekta koristili smo in vivo model
na pacovima sa aritmijom izazvanom akonitinom. 5OCl-PF je ubrzao pojavu
supraventrikularnih prevremenih otkucaja (SVPB) i smrt više nego akonitin. Sve životinje
lečene sa 5OCl-PF razvile su ventrikularne prevremene otkucaje (VPBS i VPBB) i
paroksizmalnu ventrikularnu tahikardiju (PVT). 5OF-PF je imao negativan hronotropni efekat i
potencirao atrijalnu ekscitabilnost (više SVPB). Pozitivno je uticao na pojavu i vreme početka
supraventrikularne tahikardije, VPBS i PVT. Na osnovu dobijenih rezultata se može zaključiti
da novosintetisani derivati propafenona nemaju bolji antiaritmijski efekat od polaznog
jedinjenja. U budućnosti, istraživanje će biti usmereno ka sintezi hemijski drugačijih derivata i
ispitivanju njihovog antiaritmijskog efekta.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Antiarrhythmic effects of newly developed propafenone derivatives, Antiaritmički efekti novosintetisanih derivata
propafenona",
volume = "72",
number = "4",
pages = "392-412",
doi = "10.5937/arhfarm72-37114"
}

Ivković, B., Opačić, D., Džudović, B., Crevar, M.,& Gojković-Bukarica, L.. (2022). Antiarrhythmic effects of newly developed propafenone derivatives. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(4), 392-412.
https://doi.org/10.5937/arhfarm72-37114

Ivković B, Opačić D, Džudović B, Crevar M, Gojković-Bukarica L. Antiarrhythmic effects of newly developed propafenone derivatives. in Arhiv za farmaciju. 2022;72(4):392-412.
doi:10.5937/arhfarm72-37114 .

Ivković, Branka, Opačić, Dragan, Džudović, Boris, Crevar, Milkica, Gojković-Bukarica, Ljiljana, "Antiarrhythmic effects of newly developed propafenone derivatives" in Arhiv za farmaciju, 72, no. 4 (2022):392-412,
https://doi.org/10.5937/arhfarm72-37114 . .

TY  - CONF
AU  - Miličević, Maja
AU  - Crevar, Milkica
AU  - Ivković, Branka
AU  - Džudović, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4599
AB  - Rivaroxaban belongs to the group of direct oral anticoagulants (DOAC), drugs used to
prevent and treat venous thrombosis and venous thromboembolism. Drugs from this group
are considered safer than vitamin K antagonists. In case of overdose, their most significant
side effect is bleeding. Given the great toxicological significance, it is very important to
develop an analytical method for quantification of this drug in biological samples. The liquid
chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of
rivaroxaban content in plasma samples was optimized and validated. Plasma samples were
prepared by protein precipitation with cold acetonitrile. Carbamazepine was used as an
internal standard. The analysis was performed on an Infinity Lab Poroshell 120 EC-C18, 4.6
×100 mm, 2.7 μm chromatographic column. The mobile phase consisted of acetonitrile and
0.1% formic acid (50:50, v/v), at a flow rate of 400 μL/min and a column temperature set at
30°C. The autosampler temperature was 4C. The injection volume was 10 μL. Detection of
analytes and internal standard was performed in multireaction monitoring mode (MRM), at
the following ion transitions: 437>145 (m/z) for rivaroxaban, and 237>194 (m/z) for the
internal standard. The optimized method was validated and the obtained parameters
indicate that the method is sensitive, specific, selective, precise and accurate. The samples
were stable under the tested conditions. A validated method has been used to determine the
concentration of rivaroxaban in plasma samples of patients with atrial fibrillation who were
hospitalized under strict medical supervision. Obtained concentrations were in the expected
range.
AB  - Rivaroksaban pripada grupi direktnih oralnih antikoagulanasa (DOAK), lekova koji se
koriste za prevenciju i lečenje venske tromboze i venske tromboembolije. Lekovi iz ove
grupe se smatraju bezbednijim od antagonista vitamina K. U slučaju predoziranja, njihov
najznačajniji neželjeni efekat je krvarenje. S obzirom na veliki toksikološki značaj, veoma je
važno postojanje analitičke metode za određivanje sadržaja ovog leka u uzorcima biološkog
materijala. Optimizovana je i validirana metoda tečne hromatografije spregnute sa masenom
spektrometrijom (LC-MS/MS) za određivanje sadržaja rivaroksabana u uzorcima plazme.
Uzorci plazme su pripremani metodom precipitacije proteina koja je vršena hladnim
acetonitrilom. Kao interni standard korišćen je karbamazepin. Analiza je izvršena na Infinity
Lab Poroshell 120 EC-C18, 4,6×100 mm, 2,7 μm hromatografskoj koloni. Mobilna faza se
sastojala od acetonitrila i 0,1% mravlje kiseline (50:50, v/v), pri protoku od 400 μL/min i
temperaturi kolone podešenoj na 30°C. Temperatura autosemplera je bila 4C. Injekciona
zapremina je bila 10 μL. Detekcija analita i internog standarda je izvršena u multireakcionom
monitoring modu (MRM), pri sledećim jonskim prelazima: 437>145 (m/z) za rivaroksaban,
odnosno 237>194 (m/z) za interni standard. Optimizovana metoda je validirana i dobijeni
parametri ukazuju da je metoda osetljiva, specifična, selektivna, precizna i tačna. Uzorci su
stabilni pri ispitivanim uslovima. Validirana metoda je primenjena za određivanje
koncentracije rivaroksabana u uzorcima plazme pacijenata sa atrijalnom fibrilacijom, koji su
bili hospitalizovani, pod strogim medicinskim nadzorom. Određene koncentracije su bile u
očekivanom opsegu.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples
T1  - Razvoj i validacija metode tečne hromatografije spregnute sa masenom spektrometrijom za određivanje sadržaja rivaroksabana u uzorcima plazme
VL  - 72
IS  - 4 suplement
SP  - S534
EP  - S535
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4599
ER  - 

@conference{
author = "Miličević, Maja and Crevar, Milkica and Ivković, Branka and Džudović, Jelena",
year = "2022",
abstract = "Rivaroxaban belongs to the group of direct oral anticoagulants (DOAC), drugs used to
prevent and treat venous thrombosis and venous thromboembolism. Drugs from this group
are considered safer than vitamin K antagonists. In case of overdose, their most significant
side effect is bleeding. Given the great toxicological significance, it is very important to
develop an analytical method for quantification of this drug in biological samples. The liquid
chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of
rivaroxaban content in plasma samples was optimized and validated. Plasma samples were
prepared by protein precipitation with cold acetonitrile. Carbamazepine was used as an
internal standard. The analysis was performed on an Infinity Lab Poroshell 120 EC-C18, 4.6
×100 mm, 2.7 μm chromatographic column. The mobile phase consisted of acetonitrile and
0.1% formic acid (50:50, v/v), at a flow rate of 400 μL/min and a column temperature set at
30°C. The autosampler temperature was 4C. The injection volume was 10 μL. Detection of
analytes and internal standard was performed in multireaction monitoring mode (MRM), at
the following ion transitions: 437>145 (m/z) for rivaroxaban, and 237>194 (m/z) for the
internal standard. The optimized method was validated and the obtained parameters
indicate that the method is sensitive, specific, selective, precise and accurate. The samples
were stable under the tested conditions. A validated method has been used to determine the
concentration of rivaroxaban in plasma samples of patients with atrial fibrillation who were
hospitalized under strict medical supervision. Obtained concentrations were in the expected
range., Rivaroksaban pripada grupi direktnih oralnih antikoagulanasa (DOAK), lekova koji se
koriste za prevenciju i lečenje venske tromboze i venske tromboembolije. Lekovi iz ove
grupe se smatraju bezbednijim od antagonista vitamina K. U slučaju predoziranja, njihov
najznačajniji neželjeni efekat je krvarenje. S obzirom na veliki toksikološki značaj, veoma je
važno postojanje analitičke metode za određivanje sadržaja ovog leka u uzorcima biološkog
materijala. Optimizovana je i validirana metoda tečne hromatografije spregnute sa masenom
spektrometrijom (LC-MS/MS) za određivanje sadržaja rivaroksabana u uzorcima plazme.
Uzorci plazme su pripremani metodom precipitacije proteina koja je vršena hladnim
acetonitrilom. Kao interni standard korišćen je karbamazepin. Analiza je izvršena na Infinity
Lab Poroshell 120 EC-C18, 4,6×100 mm, 2,7 μm hromatografskoj koloni. Mobilna faza se
sastojala od acetonitrila i 0,1% mravlje kiseline (50:50, v/v), pri protoku od 400 μL/min i
temperaturi kolone podešenoj na 30°C. Temperatura autosemplera je bila 4C. Injekciona
zapremina je bila 10 μL. Detekcija analita i internog standarda je izvršena u multireakcionom
monitoring modu (MRM), pri sledećim jonskim prelazima: 437>145 (m/z) za rivaroksaban,
odnosno 237>194 (m/z) za interni standard. Optimizovana metoda je validirana i dobijeni
parametri ukazuju da je metoda osetljiva, specifična, selektivna, precizna i tačna. Uzorci su
stabilni pri ispitivanim uslovima. Validirana metoda je primenjena za određivanje
koncentracije rivaroksabana u uzorcima plazme pacijenata sa atrijalnom fibrilacijom, koji su
bili hospitalizovani, pod strogim medicinskim nadzorom. Određene koncentracije su bile u
očekivanom opsegu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples, Razvoj i validacija metode tečne hromatografije spregnute sa masenom spektrometrijom za određivanje sadržaja rivaroksabana u uzorcima plazme",
volume = "72",
number = "4 suplement",
pages = "S534-S535",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4599"
}

Miličević, M., Crevar, M., Ivković, B.,& Džudović, J.. (2022). Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S534-S535.
https://hdl.handle.net/21.15107/rcub_farfar_4599

Miličević M, Crevar M, Ivković B, Džudović J. Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples. in Arhiv za farmaciju. 2022;72(4 suplement):S534-S535.
https://hdl.handle.net/21.15107/rcub_farfar_4599 .

Miličević, Maja, Crevar, Milkica, Ivković, Branka, Džudović, Jelena, "Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S534-S535,
https://hdl.handle.net/21.15107/rcub_farfar_4599 .

TY  - JOUR
AU  - Madžarević, Marijana
AU  - Medarević, Đorđe
AU  - Pavlović, Stefan
AU  - Ivković, Branka
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5544
AB  - Selective laser sintering (SLS) is a rapid prototyping technique for the production of
three-dimensional objects through selectively sintering powder-based layer materials. The aim
of the study was to investigate the effect of energy density (ED) and formulation factors on the
printability and characteristics of SLS irbesartan tablets. The correlation between formulation factors,
ED, and printability was obtained using a decision tree model with an accuracy of 80%. FT-IR
results revealed that there was no interaction between irbesartan and the applied excipients. DSC
results indicated that irbesartan was present in an amorphous form in printed tablets. ED had a
significant influence on tablets’ physical, mechanical, and morphological characteristics. Adding
lactose monohydrate enabled faster drug release while reducing the possibility for printing with
different laser speeds. However, formulations with crospovidone were printable with a wider range
of laser speeds. The adjustment of formulation and process parameters enabled the production of SLS
tablets with hydroxypropyl methylcellulose with complete release in less than 30 min. The results
suggest that a decision tree could be a useful tool for predicting the printability of pharmaceutical
formulations. Tailoring the characteristics of SLS irbesartan tablets by ED is possible; however,
it needs to be governed by the composition of the whole formulation.
PB  - MDPI
T2  - Pharmaceutics
T1  - Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model
VL  - 13
IS  - 11
SP  - 1969
DO  - 10.3390/pharmaceutics13111969
ER  - 

@article{
author = "Madžarević, Marijana and Medarević, Đorđe and Pavlović, Stefan and Ivković, Branka and Đuriš, Jelena and Ibrić, Svetlana",
year = "2021",
abstract = "Selective laser sintering (SLS) is a rapid prototyping technique for the production of
three-dimensional objects through selectively sintering powder-based layer materials. The aim
of the study was to investigate the effect of energy density (ED) and formulation factors on the
printability and characteristics of SLS irbesartan tablets. The correlation between formulation factors,
ED, and printability was obtained using a decision tree model with an accuracy of 80%. FT-IR
results revealed that there was no interaction between irbesartan and the applied excipients. DSC
results indicated that irbesartan was present in an amorphous form in printed tablets. ED had a
significant influence on tablets’ physical, mechanical, and morphological characteristics. Adding
lactose monohydrate enabled faster drug release while reducing the possibility for printing with
different laser speeds. However, formulations with crospovidone were printable with a wider range
of laser speeds. The adjustment of formulation and process parameters enabled the production of SLS
tablets with hydroxypropyl methylcellulose with complete release in less than 30 min. The results
suggest that a decision tree could be a useful tool for predicting the printability of pharmaceutical
formulations. Tailoring the characteristics of SLS irbesartan tablets by ED is possible; however,
it needs to be governed by the composition of the whole formulation.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model",
volume = "13",
number = "11",
pages = "1969",
doi = "10.3390/pharmaceutics13111969"
}

Madžarević, M., Medarević, Đ., Pavlović, S., Ivković, B., Đuriš, J.,& Ibrić, S.. (2021). Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model. in Pharmaceutics
MDPI., 13(11), 1969.
https://doi.org/10.3390/pharmaceutics13111969

Madžarević M, Medarević Đ, Pavlović S, Ivković B, Đuriš J, Ibrić S. Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model. in Pharmaceutics. 2021;13(11):1969.
doi:10.3390/pharmaceutics13111969 .

Madžarević, Marijana, Medarević, Đorđe, Pavlović, Stefan, Ivković, Branka, Đuriš, Jelena, Ibrić, Svetlana, "Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model" in Pharmaceutics, 13, no. 11 (2021):1969,
https://doi.org/10.3390/pharmaceutics13111969 . .

TY  - CONF
AU  - Pešić, Nikola
AU  - Dapčević, Aleksandra
AU  - Ivković, Branka
AU  - Barudžija, Tanja
AU  - Krkobabić, Mirjana
AU  - Ibrić, Svetlana
AU  - Medarević, Đorđe
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5327
AB  - INTRODUCTION
The development of formulations with amorphous form of drug is one of the most commonly used approaches for improving solubility and bioavailability of poorly soluble drugs. Solid dispersions with different hydrophilic polymers have been widely investigated during the last decades as an approach for development of stable formulations with amorphous drug. However, high weight percentage of polymer is usually required to ensure molecular mixing with drug and stability against drug recrystallization, making difficult formulation of final dosage form [1]. In the last years, formulations of co-amorphous systems, where amorphous drug is stabilized with low molecular weight components (drug or excipient) have been successfully used for improving solubility and bioavailability of poorly soluble drugs, with overcoming limitations of solid dispersions [2]. This study investigated effect of three amino acids (AAs) on amorphization of carvedilol (CRV) by dry milling process, with the overall aim to improve CRV dissolution.
EXPERIMENTAL METHODS
Materials
CRV (Hemofarm a.d., Serbia) was used as a model poorly soluble drug. L-tryptophan (TRY, Carl Roth, Germany), L-phenylalanine (PHE, Carl Roth, Germany) and L-lysine (LYS, Acros Organics, Belgium) were used as AAs.
Samples preparation and physicochemical characterization
Mixture of CRV and each of AAs in CRV:AAs molar ratios 1:0.5, 1:1 and 1:2 were placed in 125 ml stainless steel milling jar and subject to milling in high-energy planetary ball mill (PM 100, Retch, Germany) during 4 h, with 30 min break after 2 h. Milling was performed using 10 milling balls of 10 mm diameter with rotation speed of mill of 400 rpm.
Changes of CRV and AAs physical state due to milling were assessed by Powder X-ray Diffraction (PXRD, Philips PW1050, The Netherlands) and Differential Scanning Calorimetry (DSC, DSC 1, Mettler Toledo, Germany). In vitro dissolution testing was performed under non-sink conditions using rotating paddle apparatus (Erweka DT70, Erweka, Germany). Samples containing 100 mg of CRV were tested in 250 ml of phosphate buffer (pH=6.8) during
8 h, with paddle rotation speed of 50 rpm. Concentration of dissolved CRV was determined by HPLC (Dionex Ultimate 3000, Thermo scientific, USA). Area under dissolution curve (AUC) was calculated for each formulation and compared with AUC of CRV dissolution profile.
RESULTS AND DISCUSSION
Presence of diffraction peaks at 6.0, 15.0, 17.65, 18.55 and 24.5° 2θ and sharp melting endotherm at 116.6 °C confirmed that raw CRV was present in crystalline polymorph form II [3]. Significant reduction in crystallinity was observed for all samples prepared with TRY and PHE, while there were no peaks of CRV and AA on the PXRD pattern of CRV:TRY 1:2 sample. This was confirmed by the DSC analysis, where melting peaks of CRV and AAs were present on the thermograms of all samples except CRV:TRY 1:2 sample. This sample showed only exotherm at 102 °C due to recrystallization of TRY, followed by its melting at 266 °C, confirming CRV amorphization induced by milling. High crystallinity on PXRD patterns of all samples milled with LYS, together with the presence of melting peaks of both CRV and AA on the DSC thermograms, showed that LYS was the least suitable AA for amorphization of CRV. Despite that TRY and PHE induced partial or complete amorphization of CRV, these AAs were less efficient in improving dissolution of CRV compared to LYS. The highest supersaturation of CRV was achieved from CRV:LYS 1:1 sample with almost 3 times higher AUC compared to pure CRV. It is evident that maximum CRV concentration from this sample was reached in the first 90 min and is maintained during the entire test. Although similar CRV concentration was achieved after 60 min for CRV:LYS 1:2 sample, it is evident that CRV concentration started to decrease after this time point.
CONCLUSION
Complete amorphization was achieved by milling of only CRV:TRY 1:2 mixture, while significant decrease in crystallinity was observed for other samples milled with TRY and PHE. Although milling of CRV with LYS resulted in samples with the highest crystallinity, samples prepared with this AA in 1:1 and 1:2 molar ratios were the most efficient in providing CRV supersaturation. CRV:LYS 1:1 molar ratio can be considered as optimal, as achieved supersaturation was maintained during 8 h.
PB  - International Association for Pharmaceutical Technology, Mainz, Germany
C3  - 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting
T1  - Evaluation of potential of amino acids for amorphization and dissolution improvement of carvedilol
SP  - 1
EP  - 2
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5327
ER  - 

@conference{
author = "Pešić, Nikola and Dapčević, Aleksandra and Ivković, Branka and Barudžija, Tanja and Krkobabić, Mirjana and Ibrić, Svetlana and Medarević, Đorđe",
year = "2021",
abstract = "INTRODUCTION
The development of formulations with amorphous form of drug is one of the most commonly used approaches for improving solubility and bioavailability of poorly soluble drugs. Solid dispersions with different hydrophilic polymers have been widely investigated during the last decades as an approach for development of stable formulations with amorphous drug. However, high weight percentage of polymer is usually required to ensure molecular mixing with drug and stability against drug recrystallization, making difficult formulation of final dosage form [1]. In the last years, formulations of co-amorphous systems, where amorphous drug is stabilized with low molecular weight components (drug or excipient) have been successfully used for improving solubility and bioavailability of poorly soluble drugs, with overcoming limitations of solid dispersions [2]. This study investigated effect of three amino acids (AAs) on amorphization of carvedilol (CRV) by dry milling process, with the overall aim to improve CRV dissolution.
EXPERIMENTAL METHODS
Materials
CRV (Hemofarm a.d., Serbia) was used as a model poorly soluble drug. L-tryptophan (TRY, Carl Roth, Germany), L-phenylalanine (PHE, Carl Roth, Germany) and L-lysine (LYS, Acros Organics, Belgium) were used as AAs.
Samples preparation and physicochemical characterization
Mixture of CRV and each of AAs in CRV:AAs molar ratios 1:0.5, 1:1 and 1:2 were placed in 125 ml stainless steel milling jar and subject to milling in high-energy planetary ball mill (PM 100, Retch, Germany) during 4 h, with 30 min break after 2 h. Milling was performed using 10 milling balls of 10 mm diameter with rotation speed of mill of 400 rpm.
Changes of CRV and AAs physical state due to milling were assessed by Powder X-ray Diffraction (PXRD, Philips PW1050, The Netherlands) and Differential Scanning Calorimetry (DSC, DSC 1, Mettler Toledo, Germany). In vitro dissolution testing was performed under non-sink conditions using rotating paddle apparatus (Erweka DT70, Erweka, Germany). Samples containing 100 mg of CRV were tested in 250 ml of phosphate buffer (pH=6.8) during
8 h, with paddle rotation speed of 50 rpm. Concentration of dissolved CRV was determined by HPLC (Dionex Ultimate 3000, Thermo scientific, USA). Area under dissolution curve (AUC) was calculated for each formulation and compared with AUC of CRV dissolution profile.
RESULTS AND DISCUSSION
Presence of diffraction peaks at 6.0, 15.0, 17.65, 18.55 and 24.5° 2θ and sharp melting endotherm at 116.6 °C confirmed that raw CRV was present in crystalline polymorph form II [3]. Significant reduction in crystallinity was observed for all samples prepared with TRY and PHE, while there were no peaks of CRV and AA on the PXRD pattern of CRV:TRY 1:2 sample. This was confirmed by the DSC analysis, where melting peaks of CRV and AAs were present on the thermograms of all samples except CRV:TRY 1:2 sample. This sample showed only exotherm at 102 °C due to recrystallization of TRY, followed by its melting at 266 °C, confirming CRV amorphization induced by milling. High crystallinity on PXRD patterns of all samples milled with LYS, together with the presence of melting peaks of both CRV and AA on the DSC thermograms, showed that LYS was the least suitable AA for amorphization of CRV. Despite that TRY and PHE induced partial or complete amorphization of CRV, these AAs were less efficient in improving dissolution of CRV compared to LYS. The highest supersaturation of CRV was achieved from CRV:LYS 1:1 sample with almost 3 times higher AUC compared to pure CRV. It is evident that maximum CRV concentration from this sample was reached in the first 90 min and is maintained during the entire test. Although similar CRV concentration was achieved after 60 min for CRV:LYS 1:2 sample, it is evident that CRV concentration started to decrease after this time point.
CONCLUSION
Complete amorphization was achieved by milling of only CRV:TRY 1:2 mixture, while significant decrease in crystallinity was observed for other samples milled with TRY and PHE. Although milling of CRV with LYS resulted in samples with the highest crystallinity, samples prepared with this AA in 1:1 and 1:2 molar ratios were the most efficient in providing CRV supersaturation. CRV:LYS 1:1 molar ratio can be considered as optimal, as achieved supersaturation was maintained during 8 h.",
publisher = "International Association for Pharmaceutical Technology, Mainz, Germany",
journal = "12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting",
title = "Evaluation of potential of amino acids for amorphization and dissolution improvement of carvedilol",
pages = "1-2",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5327"
}

Pešić, N., Dapčević, A., Ivković, B., Barudžija, T., Krkobabić, M., Ibrić, S.,& Medarević, Đ.. (2021). Evaluation of potential of amino acids for amorphization and dissolution improvement of carvedilol. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting
International Association for Pharmaceutical Technology, Mainz, Germany., 1-2.
https://hdl.handle.net/21.15107/rcub_farfar_5327

Pešić N, Dapčević A, Ivković B, Barudžija T, Krkobabić M, Ibrić S, Medarević Đ. Evaluation of potential of amino acids for amorphization and dissolution improvement of carvedilol. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting. 2021;:1-2.
https://hdl.handle.net/21.15107/rcub_farfar_5327 .

Pešić, Nikola, Dapčević, Aleksandra, Ivković, Branka, Barudžija, Tanja, Krkobabić, Mirjana, Ibrić, Svetlana, Medarević, Đorđe, "Evaluation of potential of amino acids for amorphization and dissolution improvement of carvedilol" in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting (2021):1-2,
https://hdl.handle.net/21.15107/rcub_farfar_5327 .

TY  - JOUR
AU  - Pešić, Nikola
AU  - Dapčević, Aleksandra
AU  - Ivković, Branka
AU  - Kachrimanis, Kyriakos
AU  - Mitrić, Miodrag
AU  - Ibrić, Svetlana
AU  - Medarević, Đorđe
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3964
AB  - In this study, four low molecular weight (LMW) excipients, tryptophan (TRY), phenylalanine (PHE), lysine (LYS) and saccharin (SAC) were evaluated as co-formers to generate co-amorphous systems (CAMS) by ball milling with carvedilol (CRV). Mixtures of CRV and LMW excipient in 1:0.5, 1:1 and 1:2 drug:excipient molar ratios were ball milled and analysed by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform (FT-IR) infrared spectroscopy and dissolution testing. CAMS were formed by milling of a mixture of CRV with TRY in 1:2 M ratio and SAC in 1:1 M ratio, while amorphization of only CRV was achieved in other mixtures with SAC. In other samples containing TRY and PHE, milling resulted in partial amorphization, while LYS was the least suitable excipient for the amorphization of CRV. Unexpectedly, the highest supersaturation of CRV was achieved from samples containing CRV and LYS in 1:1 and 1:2 M ratios, despite the absence of a significant reduction in CRV crystallinity upon milling of these samples. Increase of hydrophobic surface area caused by milling of samples with TRY and PHE and agglomeration during dissolution testing of samples containing SAC are likely causes of poor dissolution performance of mixtures containing fully or partially amorphous CRV.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol
VL  - 608
DO  - 10.1016/j.ijpharm.2021.121033
ER  - 

@article{
author = "Pešić, Nikola and Dapčević, Aleksandra and Ivković, Branka and Kachrimanis, Kyriakos and Mitrić, Miodrag and Ibrić, Svetlana and Medarević, Đorđe",
year = "2021",
abstract = "In this study, four low molecular weight (LMW) excipients, tryptophan (TRY), phenylalanine (PHE), lysine (LYS) and saccharin (SAC) were evaluated as co-formers to generate co-amorphous systems (CAMS) by ball milling with carvedilol (CRV). Mixtures of CRV and LMW excipient in 1:0.5, 1:1 and 1:2 drug:excipient molar ratios were ball milled and analysed by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform (FT-IR) infrared spectroscopy and dissolution testing. CAMS were formed by milling of a mixture of CRV with TRY in 1:2 M ratio and SAC in 1:1 M ratio, while amorphization of only CRV was achieved in other mixtures with SAC. In other samples containing TRY and PHE, milling resulted in partial amorphization, while LYS was the least suitable excipient for the amorphization of CRV. Unexpectedly, the highest supersaturation of CRV was achieved from samples containing CRV and LYS in 1:1 and 1:2 M ratios, despite the absence of a significant reduction in CRV crystallinity upon milling of these samples. Increase of hydrophobic surface area caused by milling of samples with TRY and PHE and agglomeration during dissolution testing of samples containing SAC are likely causes of poor dissolution performance of mixtures containing fully or partially amorphous CRV.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol",
volume = "608",
doi = "10.1016/j.ijpharm.2021.121033"
}

Pešić, N., Dapčević, A., Ivković, B., Kachrimanis, K., Mitrić, M., Ibrić, S.,& Medarević, Đ.. (2021). Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol. in International Journal of Pharmaceutics
Elsevier B.V.., 608.
https://doi.org/10.1016/j.ijpharm.2021.121033

Pešić N, Dapčević A, Ivković B, Kachrimanis K, Mitrić M, Ibrić S, Medarević Đ. Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol. in International Journal of Pharmaceutics. 2021;608.
doi:10.1016/j.ijpharm.2021.121033 .

Pešić, Nikola, Dapčević, Aleksandra, Ivković, Branka, Kachrimanis, Kyriakos, Mitrić, Miodrag, Ibrić, Svetlana, Medarević, Đorđe, "Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol" in International Journal of Pharmaceutics, 608 (2021),
https://doi.org/10.1016/j.ijpharm.2021.121033 . .

TY  - JOUR
AU  - Đuranović, Marija
AU  - Madžarević, Marijana
AU  - Ivković, Branka
AU  - Ibrić, Svetlana
AU  - Cvijić, Sandra
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4088
AB  - Paracetamol-loaded tablets were printed by fused deposition modelling technique, using polyvinyl alcohol as a backbone polymer and Affinisol™ HPMC as a plasticizer in all formulations. Four different strategies were applied in order to accelerate the drug release from the tablets. First, different release enhancers were added: sodium starch glycolate, croscarmellose sodium, Kollidon CL and mannitol. Kollidon CL and mannitol showed the greatest influence on the drug dissolution rate. The second strategy included lowering the infill density, which did not make any significant changes in dissolution profiles, according to the calculated similarity factor. Then the best two release enhancers from the first strategy were combined (Kollidon CL and mannitol) and this proved to be the most effective in the drug release acceleration. The fourth strategy, increasing the percentage of the release enhancers in formulation, revealed the importance of their concentration limits. In summary, the drug release accelerated from 58% released after 5 h to reaching the plateau within 2 h. In silico physiologically-based biopharmaceutics modelling showed that formulations with mannitol and Kollidon CL, especially the formulation containing a combination of these release enhancers, can provide relatively fast drug release and extent of drug absorption that complies with an immediate release tablet.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment
VL  - 610
DO  - 10.1016/j.ijpharm.2021.121194
ER  - 

@article{
author = "Đuranović, Marija and Madžarević, Marijana and Ivković, Branka and Ibrić, Svetlana and Cvijić, Sandra",
year = "2021",
abstract = "Paracetamol-loaded tablets were printed by fused deposition modelling technique, using polyvinyl alcohol as a backbone polymer and Affinisol™ HPMC as a plasticizer in all formulations. Four different strategies were applied in order to accelerate the drug release from the tablets. First, different release enhancers were added: sodium starch glycolate, croscarmellose sodium, Kollidon CL and mannitol. Kollidon CL and mannitol showed the greatest influence on the drug dissolution rate. The second strategy included lowering the infill density, which did not make any significant changes in dissolution profiles, according to the calculated similarity factor. Then the best two release enhancers from the first strategy were combined (Kollidon CL and mannitol) and this proved to be the most effective in the drug release acceleration. The fourth strategy, increasing the percentage of the release enhancers in formulation, revealed the importance of their concentration limits. In summary, the drug release accelerated from 58% released after 5 h to reaching the plateau within 2 h. In silico physiologically-based biopharmaceutics modelling showed that formulations with mannitol and Kollidon CL, especially the formulation containing a combination of these release enhancers, can provide relatively fast drug release and extent of drug absorption that complies with an immediate release tablet.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment",
volume = "610",
doi = "10.1016/j.ijpharm.2021.121194"
}

Đuranović, M., Madžarević, M., Ivković, B., Ibrić, S.,& Cvijić, S.. (2021). The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment. in International Journal of Pharmaceutics
Elsevier B.V.., 610.
https://doi.org/10.1016/j.ijpharm.2021.121194

Đuranović M, Madžarević M, Ivković B, Ibrić S, Cvijić S. The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment. in International Journal of Pharmaceutics. 2021;610.
doi:10.1016/j.ijpharm.2021.121194 .

Đuranović, Marija, Madžarević, Marijana, Ivković, Branka, Ibrić, Svetlana, Cvijić, Sandra, "The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment" in International Journal of Pharmaceutics, 610 (2021),
https://doi.org/10.1016/j.ijpharm.2021.121194 . .