TY  - JOUR
AU  - Đuriš, Jelena
AU  - Cirin-Varađan, Slobodanka
AU  - Aleksić, Ivana
AU  - Đuriš, Mihal
AU  - Cvijić, Sandra
AU  - Ibrić, Svetlana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4693
AB  - Co-processing (CP) provides superior properties to excipients and has become a reliable option to facilitated formulation and manufacturing of variety of solid dosage forms. Development of directly compressible formulations with high doses of poorly flowing/compressible active pharmaceutical ingredients, such as paracetamol, remains a great challenge for the pharmaceutical industry due to the lack of understanding of the interplay between the formulation properties, process of compaction, and stages of tablets’ detachment and ejection. The aim of this study was to analyze the influence of the compression load, excipients’ co-processing and the addition of paracetamol on the obtained tablets’ tensile strength and the specific parameters of the tableting process, such as (net) compression work, elastic recovery, detachment, and ejection work, as well as the ejection force. Two types of neural networks were used to analyze the data: classification (Kohonen network) and regression networks (multilayer perceptron and radial basis function), to build prediction models and identify the variables that are predominantly affecting the tableting process and the obtained tablets’ tensile strength. It has been demonstrated that sophisticated data-mining methods are necessary to interpret complex phenomena regarding the effect of co-processing on tableting properties of directly compressible excipients.
PB  - MDPI
T2  - Pharmaceutics
T1  - Application of machine-learning algorithms for better understanding of tableting properties of lactose co-processed with lipid excipients
VL  - 13
IS  - 5
SP  - 663
DO  - 10.3390/pharmaceutics13050663
ER  - 

@article{
author = "Đuriš, Jelena and Cirin-Varađan, Slobodanka and Aleksić, Ivana and Đuriš, Mihal and Cvijić, Sandra and Ibrić, Svetlana",
year = "2021",
abstract = "Co-processing (CP) provides superior properties to excipients and has become a reliable option to facilitated formulation and manufacturing of variety of solid dosage forms. Development of directly compressible formulations with high doses of poorly flowing/compressible active pharmaceutical ingredients, such as paracetamol, remains a great challenge for the pharmaceutical industry due to the lack of understanding of the interplay between the formulation properties, process of compaction, and stages of tablets’ detachment and ejection. The aim of this study was to analyze the influence of the compression load, excipients’ co-processing and the addition of paracetamol on the obtained tablets’ tensile strength and the specific parameters of the tableting process, such as (net) compression work, elastic recovery, detachment, and ejection work, as well as the ejection force. Two types of neural networks were used to analyze the data: classification (Kohonen network) and regression networks (multilayer perceptron and radial basis function), to build prediction models and identify the variables that are predominantly affecting the tableting process and the obtained tablets’ tensile strength. It has been demonstrated that sophisticated data-mining methods are necessary to interpret complex phenomena regarding the effect of co-processing on tableting properties of directly compressible excipients.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Application of machine-learning algorithms for better understanding of tableting properties of lactose co-processed with lipid excipients",
volume = "13",
number = "5",
pages = "663",
doi = "10.3390/pharmaceutics13050663"
}

Đuriš, J., Cirin-Varađan, S., Aleksić, I., Đuriš, M., Cvijić, S.,& Ibrić, S.. (2021). Application of machine-learning algorithms for better understanding of tableting properties of lactose co-processed with lipid excipients. in Pharmaceutics
MDPI., 13(5), 663.
https://doi.org/10.3390/pharmaceutics13050663

Đuriš J, Cirin-Varađan S, Aleksić I, Đuriš M, Cvijić S, Ibrić S. Application of machine-learning algorithms for better understanding of tableting properties of lactose co-processed with lipid excipients. in Pharmaceutics. 2021;13(5):663.
doi:10.3390/pharmaceutics13050663 .

Đuriš, Jelena, Cirin-Varađan, Slobodanka, Aleksić, Ivana, Đuriš, Mihal, Cvijić, Sandra, Ibrić, Svetlana, "Application of machine-learning algorithms for better understanding of tableting properties of lactose co-processed with lipid excipients" in Pharmaceutics, 13, no. 5 (2021):663,
https://doi.org/10.3390/pharmaceutics13050663 . .

TY  - JOUR
AU  - Madžarević, Marijana
AU  - Medarević, Đorđe
AU  - Pavlović, Stefan
AU  - Ivković, Branka
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4852
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 mon-ohydrate 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 mon-ohydrate 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  - JOUR
AU  - Mudrić, Jelena
AU  - Šavikin, Katarina
AU  - Đekić, Ljiljana
AU  - Pavlović, Stefan
AU  - Kurćubić, Ivana
AU  - Ibrić, Svetlana
AU  - Đuriš, Jelena
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4891
AB  - Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion–melt dispersion technique, with GRE as the inner water phase, Gelucire® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determination of yield, encapsulation efficiency, and flow properties. Furthermore, in vitro dissolution of gentiopicroside, the size of the dispersed systems, mechanical properties, and mucoadhesion of tablets obtained by direct compression were investigated. The results have revealed that SLM with the macroporous structure were formulated, and, consequently, the powders floated immediately in the acidic medium. Formulation with porous silica (Sylysia® 350) and Gelucire® 43/01 as a solid lipid was characterized with the high yield end encapsulation efficiency. Furthermore, the mucoadhesive properties of tablets obtained by direct compression of that formulation, as well as the biphasic release of gentiopicroside, presence of nanoassociates in dissolution medium, and optimal mechanical properties indicated that a promising lipid-based gastroretentive system for GRE was developed.
PB  - MDPI
T2  - Pharmaceutics
T1  - Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion-Melt Dispersion Technique
VL  - 13
IS  - 12
SP  - 2095
DO  - 10.3390/pharmaceutics13122095
ER  - 

@article{
author = "Mudrić, Jelena and Šavikin, Katarina and Đekić, Ljiljana and Pavlović, Stefan and Kurćubić, Ivana and Ibrić, Svetlana and Đuriš, Jelena",
year = "2021",
abstract = "Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion–melt dispersion technique, with GRE as the inner water phase, Gelucire® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determination of yield, encapsulation efficiency, and flow properties. Furthermore, in vitro dissolution of gentiopicroside, the size of the dispersed systems, mechanical properties, and mucoadhesion of tablets obtained by direct compression were investigated. The results have revealed that SLM with the macroporous structure were formulated, and, consequently, the powders floated immediately in the acidic medium. Formulation with porous silica (Sylysia® 350) and Gelucire® 43/01 as a solid lipid was characterized with the high yield end encapsulation efficiency. Furthermore, the mucoadhesive properties of tablets obtained by direct compression of that formulation, as well as the biphasic release of gentiopicroside, presence of nanoassociates in dissolution medium, and optimal mechanical properties indicated that a promising lipid-based gastroretentive system for GRE was developed.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion-Melt Dispersion Technique",
volume = "13",
number = "12",
pages = "2095",
doi = "10.3390/pharmaceutics13122095"
}

Mudrić, J., Šavikin, K., Đekić, L., Pavlović, S., Kurćubić, I., Ibrić, S.,& Đuriš, J.. (2021). Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion-Melt Dispersion Technique. in Pharmaceutics
MDPI., 13(12), 2095.
https://doi.org/10.3390/pharmaceutics13122095

Mudrić J, Šavikin K, Đekić L, Pavlović S, Kurćubić I, Ibrić S, Đuriš J. Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion-Melt Dispersion Technique. in Pharmaceutics. 2021;13(12):2095.
doi:10.3390/pharmaceutics13122095 .

Mudrić, Jelena, Šavikin, Katarina, Đekić, Ljiljana, Pavlović, Stefan, Kurćubić, Ivana, Ibrić, Svetlana, Đuriš, Jelena, "Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion-Melt Dispersion Technique" in Pharmaceutics, 13, no. 12 (2021):2095,
https://doi.org/10.3390/pharmaceutics13122095 . .

TY  - JOUR
AU  - Milovanović, Stoja
AU  - Đuriš, Jelena
AU  - Dapčević, Aleksandra
AU  - Lučić-Škorić, Marija
AU  - Medarević, Đorđe
AU  - Pavlović, Stefan
AU  - Ibrić, Svetlana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4198
AB  - This study investigates pharmaceutical polymers (Soluplus®, HPMCAS, and Eudragit® E100) and supercritical CO2-assisted process for preparation of floating valsartan delivery systems. Tested process (at pressure of 30 MPa and temperature of 100 °C during 2 h) enabled preparation of stable porous valsartan formulations which was confirmed with FESEM and mercury intrusion porosimetry analysis. The bulk density of obtained formulations was lower than 550 kg/m3. FTIR, DSC, and PXRD analysis indicated that there was no chemical interaction between the drug and polymers and that amorphous solid dispersions were obtained. Formulations with Soluplus® and HPMCAS retained its buoyancy in 0.1 M HCl for longer than 24 h, while formulation with Eudragit® E100 retained its buoyancy up to 2 h. Controlled valsartan release was influenced by solubility of polymers in the tested release medium, which was confirmed by UV/VIS spectroscopy. The obtained results provided framework for further development of floating drug delivery system using an environmental friendly process.
PB  - Springer
T2  - Journal of Polymer Research
T1  - Preparation of floating polymer-valsartan delivery systems using supercritical CO2
VL  - 28
SP  - 74
DO  - 10.1007/s10965-021-02440-1
ER  - 

@article{
author = "Milovanović, Stoja and Đuriš, Jelena and Dapčević, Aleksandra and Lučić-Škorić, Marija and Medarević, Đorđe and Pavlović, Stefan and Ibrić, Svetlana",
year = "2021",
abstract = "This study investigates pharmaceutical polymers (Soluplus®, HPMCAS, and Eudragit® E100) and supercritical CO2-assisted process for preparation of floating valsartan delivery systems. Tested process (at pressure of 30 MPa and temperature of 100 °C during 2 h) enabled preparation of stable porous valsartan formulations which was confirmed with FESEM and mercury intrusion porosimetry analysis. The bulk density of obtained formulations was lower than 550 kg/m3. FTIR, DSC, and PXRD analysis indicated that there was no chemical interaction between the drug and polymers and that amorphous solid dispersions were obtained. Formulations with Soluplus® and HPMCAS retained its buoyancy in 0.1 M HCl for longer than 24 h, while formulation with Eudragit® E100 retained its buoyancy up to 2 h. Controlled valsartan release was influenced by solubility of polymers in the tested release medium, which was confirmed by UV/VIS spectroscopy. The obtained results provided framework for further development of floating drug delivery system using an environmental friendly process.",
publisher = "Springer",
journal = "Journal of Polymer Research",
title = "Preparation of floating polymer-valsartan delivery systems using supercritical CO2",
volume = "28",
pages = "74",
doi = "10.1007/s10965-021-02440-1"
}

Milovanović, S., Đuriš, J., Dapčević, A., Lučić-Škorić, M., Medarević, Đ., Pavlović, S.,& Ibrić, S.. (2021). Preparation of floating polymer-valsartan delivery systems using supercritical CO2. in Journal of Polymer Research
Springer., 28, 74.
https://doi.org/10.1007/s10965-021-02440-1

Milovanović S, Đuriš J, Dapčević A, Lučić-Škorić M, Medarević Đ, Pavlović S, Ibrić S. Preparation of floating polymer-valsartan delivery systems using supercritical CO2. in Journal of Polymer Research. 2021;28:74.
doi:10.1007/s10965-021-02440-1 .

Milovanović, Stoja, Đuriš, Jelena, Dapčević, Aleksandra, Lučić-Škorić, Marija, Medarević, Đorđe, Pavlović, Stefan, Ibrić, Svetlana, "Preparation of floating polymer-valsartan delivery systems using supercritical CO2" in Journal of Polymer Research, 28 (2021):74,
https://doi.org/10.1007/s10965-021-02440-1 . .

TY  - JOUR
AU  - Solomun, L
AU  - Ibrić, Svetlana
AU  - Vajs, Vlatka
AU  - Vuković, Ivan
AU  - Vujić, Z
PY  - 2010
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2778
AB  - In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form, i.e., freeze-dried powder for injections, was examined. The goal was to evaluate the chemical stabilities of methylprednisolone sodium succinate packaged in a dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. The method proposed by United States Pharmacopeia was used to determine concentrations of methylprednisolone, as the sum of the concentration of methylprednisolone esters (17-hydrogen succinate and 21-hydrogen succinate) and free methylprednisolone. The HPLC method was used for stability evaluation of the active substance and determination of related substances. Four main degradation products were registered. Temperature has a major impact on the degradation process with the appearance of 3 degradation products (impurities B, C and D), while the presence of light caused an increasing content of impurity A. Identification of impurity B, C and D has been realized using mass and NMR spectroscopy. All three substances are substances related to methylprednisolone. © 2010 (CC) SCS.
AB  - У овом раду испитиване су особине фармаколошки активне супстанце метилпреднизолона (у облику метилпреднизолон-натријум-сукцината) у готовом производу – лиофилизату за раствор за инјекције. Циљ рада је испитивање хемијске стабилности метилпреднизолон-натријум-сукцината у двокоморној бочици, као специфичном систему контактног паковања. Испитан је ефекат различитих параметара: температуре, влаге и светлости. За одређивање концентрације метилпреднизолона, као збирне концентрације метилпреднизолон естара (17-хидроген-сукцината и 21-хидроген-сукцината) и слободног метилпреднизолона, коришћена је метода описана у Америчкој фармакопеји. За испитивање сродних супстанци примењена је HPLC метода. Уочена су 4 деградациона производа. Доказано је да повећање температуре има највећи значај на процес деградације и утиче на повећање садржаја нечистоћа B, C и D, док присуство светлости доводи до повећања садржаја нечистоће А. Нечистоће B, C и D су идентификоване применом масене и NMR спектроскопије. Све три нечистоће су идентификоване као сродне супстанце метилпреднизолона.
T2  - Journal of the Serbian Chemical Society
T1  - Methylprednisolone and its related substances in freeze-dried powders for injections
T1  - Метилпреднизолон и његове сродне супстанце у лиофилизату за раствор за инјекције
VL  - 75
IS  - 10
SP  - 1441
EP  - 1452
DO  - 10.2298/JSC100115087S
ER  - 

@article{
author = "Solomun, L and Ibrić, Svetlana and Vajs, Vlatka and Vuković, Ivan and Vujić, Z",
year = "2010",
abstract = "In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form, i.e., freeze-dried powder for injections, was examined. The goal was to evaluate the chemical stabilities of methylprednisolone sodium succinate packaged in a dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. The method proposed by United States Pharmacopeia was used to determine concentrations of methylprednisolone, as the sum of the concentration of methylprednisolone esters (17-hydrogen succinate and 21-hydrogen succinate) and free methylprednisolone. The HPLC method was used for stability evaluation of the active substance and determination of related substances. Four main degradation products were registered. Temperature has a major impact on the degradation process with the appearance of 3 degradation products (impurities B, C and D), while the presence of light caused an increasing content of impurity A. Identification of impurity B, C and D has been realized using mass and NMR spectroscopy. All three substances are substances related to methylprednisolone. © 2010 (CC) SCS., У овом раду испитиване су особине фармаколошки активне супстанце метилпреднизолона (у облику метилпреднизолон-натријум-сукцината) у готовом производу – лиофилизату за раствор за инјекције. Циљ рада је испитивање хемијске стабилности метилпреднизолон-натријум-сукцината у двокоморној бочици, као специфичном систему контактног паковања. Испитан је ефекат различитих параметара: температуре, влаге и светлости. За одређивање концентрације метилпреднизолона, као збирне концентрације метилпреднизолон естара (17-хидроген-сукцината и 21-хидроген-сукцината) и слободног метилпреднизолона, коришћена је метода описана у Америчкој фармакопеји. За испитивање сродних супстанци примењена је HPLC метода. Уочена су 4 деградациона производа. Доказано је да повећање температуре има највећи значај на процес деградације и утиче на повећање садржаја нечистоћа B, C и D, док присуство светлости доводи до повећања садржаја нечистоће А. Нечистоће B, C и D су идентификоване применом масене и NMR спектроскопије. Све три нечистоће су идентификоване као сродне супстанце метилпреднизолона.",
journal = "Journal of the Serbian Chemical Society",
title = "Methylprednisolone and its related substances in freeze-dried powders for injections, Метилпреднизолон и његове сродне супстанце у лиофилизату за раствор за инјекције",
volume = "75",
number = "10",
pages = "1441-1452",
doi = "10.2298/JSC100115087S"
}

Solomun, L., Ibrić, S., Vajs, V., Vuković, I.,& Vujić, Z.. (2010). Methylprednisolone and its related substances in freeze-dried powders for injections. in Journal of the Serbian Chemical Society, 75(10), 1441-1452.
https://doi.org/10.2298/JSC100115087S

Solomun L, Ibrić S, Vajs V, Vuković I, Vujić Z. Methylprednisolone and its related substances in freeze-dried powders for injections. in Journal of the Serbian Chemical Society. 2010;75(10):1441-1452.
doi:10.2298/JSC100115087S .

Solomun, L, Ibrić, Svetlana, Vajs, Vlatka, Vuković, Ivan, Vujić, Z, "Methylprednisolone and its related substances in freeze-dried powders for injections" in Journal of the Serbian Chemical Society, 75, no. 10 (2010):1441-1452,
https://doi.org/10.2298/JSC100115087S . .