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  - JOUR
AU  - Salatić, Petra
AU  - Gudelj, Martina
AU  - Krstić, Marko
AU  - Jurko, Lucija
AU  - Bošković, Perica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4254
AB  - Microemulsions are optically isotropic and thermodynamically stable systems of water, oil and surfactant, often in
combination with a cosurfactant which is required for optimal formation of microemulsion with a smaller
aggregate radius and greater curvature of the interfacial layer. The full potential of microemulsion systems has yet
to be realized and a lot of innovation in the field of microemulsion technology is expected. They have numerous
advantages due to spontaneous formation, ease of manufacturing and scale-up, thermodynamic stability, ability to
improve drug solubilization, and bioavailability. This work describes microemulsion systems which contain
nonionic surfactants Tween 80 and Span 80, isopropyl myristate as the oil phase and purified water. From the most
suitable microemulsion region, samples were selected and analyzed, blank and with encapsulated ascorbic acid, by
measuring the size distribution of microemulsion aggregates, refractive index, electrical conductivity, and surface
tension.
AB  - Мікроемульсії є оптично ізотропними і термодинамічно стабільними системами, що складаються з води, олії
і поверхнево-активної речовини, часто у поєднанні з ко-сурфактантом, який потрібний для оптимального
формування мікроемульсії з меншим агрегатним радіусом і більшою кривизною міжфазного шару.
Потенціал мікроемульсій ще не повністю реалізований, і тому очікується багато інновацій в області
технології мікроемульсій. Вони мають численні переваги завдяки спонтанному утворенню, простоті
виробництва і масштабування, термодинамічній стабільності, здатності покращувати солюбілізацію ліків і
біодоступність. У цій роботі описані мікроемульсивні системи, що містять неіонні поверхнево-активні
речовини Tween 80 і Span 80, ізопропілмирістат в якості масляної фази і очищену воду. За допомогою
вимірювань розподілу розмірів мікроемульсивних агрегатів, показника заломлення, електропровідності і
поверхневого натягу з найбільш відповідної області мікроемульсії були відібрані і проаналізовані зразки, як
порожні, так і з інкапсульованою аскорбіновою кислотою.
PB  - Oles Honchar Dnipro National University
T2  - Journal of Chemistry and Technologies
T1  - MICROEMULSION „WATER IN OIL“ AS A POTENTIAL SYSTEM FOR ASCORBIC ACID ENCAPSULATION
T1  - МІКРОЕМУЛЬСІЯ «ВОДА В ОЛІЇ» ЯК ПОТЕНЦІЙНА СИСТЕМА ДЛЯ ІНКАПСУЛЯЦІЇ АСКОРБІНОВОЇ КИСЛОТИ
VL  - 30
IS  - 2
SP  - 192
EP  - 197
DO  - 10.15421/jchemtech.v30i2.254368
ER  - 

@article{
author = "Salatić, Petra and Gudelj, Martina and Krstić, Marko and Jurko, Lucija and Bošković, Perica",
year = "2022",
abstract = "Microemulsions are optically isotropic and thermodynamically stable systems of water, oil and surfactant, often in
combination with a cosurfactant which is required for optimal formation of microemulsion with a smaller
aggregate radius and greater curvature of the interfacial layer. The full potential of microemulsion systems has yet
to be realized and a lot of innovation in the field of microemulsion technology is expected. They have numerous
advantages due to spontaneous formation, ease of manufacturing and scale-up, thermodynamic stability, ability to
improve drug solubilization, and bioavailability. This work describes microemulsion systems which contain
nonionic surfactants Tween 80 and Span 80, isopropyl myristate as the oil phase and purified water. From the most
suitable microemulsion region, samples were selected and analyzed, blank and with encapsulated ascorbic acid, by
measuring the size distribution of microemulsion aggregates, refractive index, electrical conductivity, and surface
tension., Мікроемульсії є оптично ізотропними і термодинамічно стабільними системами, що складаються з води, олії
і поверхнево-активної речовини, часто у поєднанні з ко-сурфактантом, який потрібний для оптимального
формування мікроемульсії з меншим агрегатним радіусом і більшою кривизною міжфазного шару.
Потенціал мікроемульсій ще не повністю реалізований, і тому очікується багато інновацій в області
технології мікроемульсій. Вони мають численні переваги завдяки спонтанному утворенню, простоті
виробництва і масштабування, термодинамічній стабільності, здатності покращувати солюбілізацію ліків і
біодоступність. У цій роботі описані мікроемульсивні системи, що містять неіонні поверхнево-активні
речовини Tween 80 і Span 80, ізопропілмирістат в якості масляної фази і очищену воду. За допомогою
вимірювань розподілу розмірів мікроемульсивних агрегатів, показника заломлення, електропровідності і
поверхневого натягу з найбільш відповідної області мікроемульсії були відібрані і проаналізовані зразки, як
порожні, так і з інкапсульованою аскорбіновою кислотою.",
publisher = "Oles Honchar Dnipro National University",
journal = "Journal of Chemistry and Technologies",
title = "MICROEMULSION „WATER IN OIL“ AS A POTENTIAL SYSTEM FOR ASCORBIC ACID ENCAPSULATION, МІКРОЕМУЛЬСІЯ «ВОДА В ОЛІЇ» ЯК ПОТЕНЦІЙНА СИСТЕМА ДЛЯ ІНКАПСУЛЯЦІЇ АСКОРБІНОВОЇ КИСЛОТИ",
volume = "30",
number = "2",
pages = "192-197",
doi = "10.15421/jchemtech.v30i2.254368"
}

Salatić, P., Gudelj, M., Krstić, M., Jurko, L.,& Bošković, P.. (2022). MICROEMULSION „WATER IN OIL“ AS A POTENTIAL SYSTEM FOR ASCORBIC ACID ENCAPSULATION. in Journal of Chemistry and Technologies
Oles Honchar Dnipro National University., 30(2), 192-197.
https://doi.org/10.15421/jchemtech.v30i2.254368

Salatić P, Gudelj M, Krstić M, Jurko L, Bošković P. MICROEMULSION „WATER IN OIL“ AS A POTENTIAL SYSTEM FOR ASCORBIC ACID ENCAPSULATION. in Journal of Chemistry and Technologies. 2022;30(2):192-197.
doi:10.15421/jchemtech.v30i2.254368 .

Salatić, Petra, Gudelj, Martina, Krstić, Marko, Jurko, Lucija, Bošković, Perica, "MICROEMULSION „WATER IN OIL“ AS A POTENTIAL SYSTEM FOR ASCORBIC ACID ENCAPSULATION" in Journal of Chemistry and Technologies, 30, no. 2 (2022):192-197,
https://doi.org/10.15421/jchemtech.v30i2.254368 . .

TY  - JOUR
AU  - Krstić, Marko
AU  - Stupar, Miloš
AU  - Đukić-Ćosić, Danijela
AU  - Baralić, Katarina
AU  - Đogo-Mračević, Svetlana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3963
AB  - This study aimed to: (i) determine the content of toxic metals and toxigenic fungi in 14 commercial herbal tea samples from the market of Belgrade, Serbia; and (ii) assess their risk to human health. After the microwave digestion (HNO3/H2O2, 7:1,v/v), toxic metal content was determined by graphite furnace atomic absorption spectroscopy (GF-AAS). The health risk as a result of Cd, Pb, As, Mn, Ni, and Cr exposure via herbal tea intake was assessed through estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI). Fungi isolated from the tested herbal tea samples were identified on the basis of colony morphology and microscopic characteristics of reproductive structures. Toxic metals concentration in herbal tea samples for Cd, Pb, As, Mn, Ni and Cr ranged 0.04-0.93, 0.09-2.54, 0.03-0.77, 1.82-651.04, 0.97-9.01, 0.49-3.47 mg/kg of dried plant material, respectively. Values of THQ for investigated toxic metals and HI were below 1, indicating the absence of human health risk. All 14 samples of the tested herbal teas were contaminated with fungi, while total count of cultivable fungi in each sample did not exceed national standards (105 CFU/g). Presence of 23 morphologically different isolates suggested moderate fungal diversity of the samples, while the highest isolation frequency (IF) of 100% was documented for Penicillium spp. and Aspergillus spp. The obtained risk assessment results suggest that all the tested samples are safe for human health regarding the toxic metal and fungal content and provide an important basis for understanding the potential risks of toxic metals and toxigenic fungi intake via commercially available herbal teas.
PB  - Academic Press Inc.
T2  - Journal of Food Composition and Analysis
T1  - Health risk assessment of toxic metals and toxigenic fungi in commercial herbal tea samples from Belgrade, Serbia
VL  - 104
DO  - 10.1016/j.jfca.2021.104159
ER  - 

@article{
author = "Krstić, Marko and Stupar, Miloš and Đukić-Ćosić, Danijela and Baralić, Katarina and Đogo-Mračević, Svetlana",
year = "2021",
abstract = "This study aimed to: (i) determine the content of toxic metals and toxigenic fungi in 14 commercial herbal tea samples from the market of Belgrade, Serbia; and (ii) assess their risk to human health. After the microwave digestion (HNO3/H2O2, 7:1,v/v), toxic metal content was determined by graphite furnace atomic absorption spectroscopy (GF-AAS). The health risk as a result of Cd, Pb, As, Mn, Ni, and Cr exposure via herbal tea intake was assessed through estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI). Fungi isolated from the tested herbal tea samples were identified on the basis of colony morphology and microscopic characteristics of reproductive structures. Toxic metals concentration in herbal tea samples for Cd, Pb, As, Mn, Ni and Cr ranged 0.04-0.93, 0.09-2.54, 0.03-0.77, 1.82-651.04, 0.97-9.01, 0.49-3.47 mg/kg of dried plant material, respectively. Values of THQ for investigated toxic metals and HI were below 1, indicating the absence of human health risk. All 14 samples of the tested herbal teas were contaminated with fungi, while total count of cultivable fungi in each sample did not exceed national standards (105 CFU/g). Presence of 23 morphologically different isolates suggested moderate fungal diversity of the samples, while the highest isolation frequency (IF) of 100% was documented for Penicillium spp. and Aspergillus spp. The obtained risk assessment results suggest that all the tested samples are safe for human health regarding the toxic metal and fungal content and provide an important basis for understanding the potential risks of toxic metals and toxigenic fungi intake via commercially available herbal teas.",
publisher = "Academic Press Inc.",
journal = "Journal of Food Composition and Analysis",
title = "Health risk assessment of toxic metals and toxigenic fungi in commercial herbal tea samples from Belgrade, Serbia",
volume = "104",
doi = "10.1016/j.jfca.2021.104159"
}

Krstić, M., Stupar, M., Đukić-Ćosić, D., Baralić, K.,& Đogo-Mračević, S.. (2021). Health risk assessment of toxic metals and toxigenic fungi in commercial herbal tea samples from Belgrade, Serbia. in Journal of Food Composition and Analysis
Academic Press Inc.., 104.
https://doi.org/10.1016/j.jfca.2021.104159

Krstić M, Stupar M, Đukić-Ćosić D, Baralić K, Đogo-Mračević S. Health risk assessment of toxic metals and toxigenic fungi in commercial herbal tea samples from Belgrade, Serbia. in Journal of Food Composition and Analysis. 2021;104.
doi:10.1016/j.jfca.2021.104159 .

Krstić, Marko, Stupar, Miloš, Đukić-Ćosić, Danijela, Baralić, Katarina, Đogo-Mračević, Svetlana, "Health risk assessment of toxic metals and toxigenic fungi in commercial herbal tea samples from Belgrade, Serbia" in Journal of Food Composition and Analysis, 104 (2021),
https://doi.org/10.1016/j.jfca.2021.104159 . .

TY  - JOUR
AU  - Đogo-Mračević, Svetlana
AU  - Krstić, Marko
AU  - Lolić, Aleksandar
AU  - Ražić, Slavica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3471
AB  - A chemical characterization and biological activity of 7 honey types (multifloral, linden, rapeseed, sunflower,
phacelia, acacia and honeydew honey) from different regions of Serbia were presented. The physicochemical
characteristics, mineral content, antioxidant and antimicrobial activity were estimated and discussed. All honeys
showed good nutritional characteristics, according to the adopted criteria of the standard codex for honey. The
concentrations of 15 elements in honey samples were determined using inductively coupled plasma optical
emission spectroscopy (ICP-OES). Limits of quantification were in the range from 0.003 mg/kg (Cd, Cr, Cu, Mn,
and Pb) to 1.50 mg/kg for sodium. Precision was expressed as relative standard deviation and its values were
lower than 1.50%. Accuracy was evaluated with certified reference material (fish protein, DORM 4, NRC and
cooking chocolate, SRM 2384, NIST) and obtained recovery percentages were 71-127%. The content of the most
abundant elements (K, Mg, and Na) and microelements (Al, Cu, Fe, Mn, Ni, Se, Si, and Zn) showed a significant
variability in accordance of their botanical and geographical origin, but also the influence of harvest conditions.
The levels of toxic metals (As, Cd, Cr, and Pb) are much lower than the maximal allowed for these metals
according to European Commission Regulation. The antioxidant activity was evaluated by DPPH
(Diphenylpicrylhydrazyl) assay while antimicrobial activity against Gram positive and Gram negative bacteria
(E. coli and S. aureus) and fungi Candidi albicans was estimated by microdilution assay. The free radical
scavenging assay (%RSA) varies significantly among the honey samples. The highest antioxidant activity was
observed with honeydew honeys (over 75% RSA) and the lowest was observed in the acacia, ranging from 22.96
to 24.57% RSA. All honeys tested in this study exhibited antibacterial activity, with inhibition of bacterial
growth, generally the higher against E. coli (80% for linden honeys) than against S. aureus (mostly much lower
than 50%). Activity against Candidi albicans was almost negligible. The dataset composed of all experimental
results was subjected to a chemometric evaluation and cluster analysis as hierarchical nonsupervised method
was applied. According to the obtained outcome of applied algorithms, both botanical and geographical origin
have important role in the elemental composition, antioxidant and antimicrobial activities.
PB  - Elsevier
T2  - Microchemical Journal
T1  - Comparative study of the chemical composition and biological potential of honey from different regions of Serbia
VL  - 152
IS  - 104420
SP  - 1
EP  - 9
DO  - 10.1016/j.microc.2019.104420
ER  - 

@article{
author = "Đogo-Mračević, Svetlana and Krstić, Marko and Lolić, Aleksandar and Ražić, Slavica",
year = "2020",
abstract = "A chemical characterization and biological activity of 7 honey types (multifloral, linden, rapeseed, sunflower,
phacelia, acacia and honeydew honey) from different regions of Serbia were presented. The physicochemical
characteristics, mineral content, antioxidant and antimicrobial activity were estimated and discussed. All honeys
showed good nutritional characteristics, according to the adopted criteria of the standard codex for honey. The
concentrations of 15 elements in honey samples were determined using inductively coupled plasma optical
emission spectroscopy (ICP-OES). Limits of quantification were in the range from 0.003 mg/kg (Cd, Cr, Cu, Mn,
and Pb) to 1.50 mg/kg for sodium. Precision was expressed as relative standard deviation and its values were
lower than 1.50%. Accuracy was evaluated with certified reference material (fish protein, DORM 4, NRC and
cooking chocolate, SRM 2384, NIST) and obtained recovery percentages were 71-127%. The content of the most
abundant elements (K, Mg, and Na) and microelements (Al, Cu, Fe, Mn, Ni, Se, Si, and Zn) showed a significant
variability in accordance of their botanical and geographical origin, but also the influence of harvest conditions.
The levels of toxic metals (As, Cd, Cr, and Pb) are much lower than the maximal allowed for these metals
according to European Commission Regulation. The antioxidant activity was evaluated by DPPH
(Diphenylpicrylhydrazyl) assay while antimicrobial activity against Gram positive and Gram negative bacteria
(E. coli and S. aureus) and fungi Candidi albicans was estimated by microdilution assay. The free radical
scavenging assay (%RSA) varies significantly among the honey samples. The highest antioxidant activity was
observed with honeydew honeys (over 75% RSA) and the lowest was observed in the acacia, ranging from 22.96
to 24.57% RSA. All honeys tested in this study exhibited antibacterial activity, with inhibition of bacterial
growth, generally the higher against E. coli (80% for linden honeys) than against S. aureus (mostly much lower
than 50%). Activity against Candidi albicans was almost negligible. The dataset composed of all experimental
results was subjected to a chemometric evaluation and cluster analysis as hierarchical nonsupervised method
was applied. According to the obtained outcome of applied algorithms, both botanical and geographical origin
have important role in the elemental composition, antioxidant and antimicrobial activities.",
publisher = "Elsevier",
journal = "Microchemical Journal",
title = "Comparative study of the chemical composition and biological potential of honey from different regions of Serbia",
volume = "152",
number = "104420",
pages = "1-9",
doi = "10.1016/j.microc.2019.104420"
}

Đogo-Mračević, S., Krstić, M., Lolić, A.,& Ražić, S.. (2020). Comparative study of the chemical composition and biological potential of honey from different regions of Serbia. in Microchemical Journal
Elsevier., 152(104420), 1-9.
https://doi.org/10.1016/j.microc.2019.104420

Đogo-Mračević S, Krstić M, Lolić A, Ražić S. Comparative study of the chemical composition and biological potential of honey from different regions of Serbia. in Microchemical Journal. 2020;152(104420):1-9.
doi:10.1016/j.microc.2019.104420 .

Đogo-Mračević, Svetlana, Krstić, Marko, Lolić, Aleksandar, Ražić, Slavica, "Comparative study of the chemical composition and biological potential of honey from different regions of Serbia" in Microchemical Journal, 152, no. 104420 (2020):1-9,
https://doi.org/10.1016/j.microc.2019.104420 . .

TY  - JOUR
AU  - Osmanović Omerdić, Ehlimana
AU  - Alagić-Džambić, Larisa
AU  - Krstić, Marko
AU  - Pašić-Kulenović, Maja
AU  - Odović, Jadranka
AU  - Vasiljević, Dragana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3637
AB  - Solid dispersions were prepared via a solvent evaporation method, employing ethanol (96%, v/v) as solvent, with three different polymers as carrier: povidone, copovidone, and poloxamer 407. Previously developed reversed-phase HPLC (RP-HPLC) methods were modified and used for the simultaneous determination of acetylsalicylic acid and clopidogrel bisulfate and after release from solid dispersions. Chromatography was carried out on a C-18 column, with a mobile phase of acetonitrile-methanol-phosphate buffer pH 3.0, UV detection at 240 nm, and a run time of 6 min. The method was validated according to International Conference of Harmonisation guidelines and validation included specificity, accuracy, precision, linearity, robustness, limit of detection (LOD), and limit of quantification (LOQ). The method is specific for determination of acetylsalicylic acid and clopidogrel bisulfate. The linearity was provided in the concentration range 0.0275-0.1375 mg/mL for acetylsalicylic acid and 0.0200-0.1000 mg/mL for clopidogrel bisulfate, with a correlation coefficient (R2 value) of 0.9999 for both active pharmaceutical ingredients (APIs). Accuracy was confirmed by calculated recoveries for acetylsalicylic acid (98.6-101.0%) and clopidogrel bisulfate (100.0-101.6%). The intra-day and the inter-day precision-calculated relative standard deviations are less than 1%, which indicates high precision of the method. The limits of detection and quantification for acetylsalicylic acid were 0.0004 and 0.0012 mg/mL, and for clopidogrel bisulfate 0.0002 mg/mL and 0.0007 mg/mL, respectively. Small variations in chromatographic conditions did not significantly affect qualitative and quantitative system responses, which proved robustness of method. The proposed RP-HPLC method was applied for simultaneous determination of clopidogrel bisulfate and acetylsalicylic acid from solid dispersions.
PB  - MDPI AG
T2  - Applied Sciences (Switzerland)
T1  - In vitro dissolution study of acetylsalicylic acid and clopidogrel bisulfate solid dispersions: Validation of the RP-HPLC method for simultaneous analysis
VL  - 10
IS  - 14
DO  - 10.3390/app10144792
ER  - 

@article{
author = "Osmanović Omerdić, Ehlimana and Alagić-Džambić, Larisa and Krstić, Marko and Pašić-Kulenović, Maja and Odović, Jadranka and Vasiljević, Dragana",
year = "2020",
abstract = "Solid dispersions were prepared via a solvent evaporation method, employing ethanol (96%, v/v) as solvent, with three different polymers as carrier: povidone, copovidone, and poloxamer 407. Previously developed reversed-phase HPLC (RP-HPLC) methods were modified and used for the simultaneous determination of acetylsalicylic acid and clopidogrel bisulfate and after release from solid dispersions. Chromatography was carried out on a C-18 column, with a mobile phase of acetonitrile-methanol-phosphate buffer pH 3.0, UV detection at 240 nm, and a run time of 6 min. The method was validated according to International Conference of Harmonisation guidelines and validation included specificity, accuracy, precision, linearity, robustness, limit of detection (LOD), and limit of quantification (LOQ). The method is specific for determination of acetylsalicylic acid and clopidogrel bisulfate. The linearity was provided in the concentration range 0.0275-0.1375 mg/mL for acetylsalicylic acid and 0.0200-0.1000 mg/mL for clopidogrel bisulfate, with a correlation coefficient (R2 value) of 0.9999 for both active pharmaceutical ingredients (APIs). Accuracy was confirmed by calculated recoveries for acetylsalicylic acid (98.6-101.0%) and clopidogrel bisulfate (100.0-101.6%). The intra-day and the inter-day precision-calculated relative standard deviations are less than 1%, which indicates high precision of the method. The limits of detection and quantification for acetylsalicylic acid were 0.0004 and 0.0012 mg/mL, and for clopidogrel bisulfate 0.0002 mg/mL and 0.0007 mg/mL, respectively. Small variations in chromatographic conditions did not significantly affect qualitative and quantitative system responses, which proved robustness of method. The proposed RP-HPLC method was applied for simultaneous determination of clopidogrel bisulfate and acetylsalicylic acid from solid dispersions.",
publisher = "MDPI AG",
journal = "Applied Sciences (Switzerland)",
title = "In vitro dissolution study of acetylsalicylic acid and clopidogrel bisulfate solid dispersions: Validation of the RP-HPLC method for simultaneous analysis",
volume = "10",
number = "14",
doi = "10.3390/app10144792"
}

Osmanović Omerdić, E., Alagić-Džambić, L., Krstić, M., Pašić-Kulenović, M., Odović, J.,& Vasiljević, D.. (2020). In vitro dissolution study of acetylsalicylic acid and clopidogrel bisulfate solid dispersions: Validation of the RP-HPLC method for simultaneous analysis. in Applied Sciences (Switzerland)
MDPI AG., 10(14).
https://doi.org/10.3390/app10144792

Osmanović Omerdić E, Alagić-Džambić L, Krstić M, Pašić-Kulenović M, Odović J, Vasiljević D. In vitro dissolution study of acetylsalicylic acid and clopidogrel bisulfate solid dispersions: Validation of the RP-HPLC method for simultaneous analysis. in Applied Sciences (Switzerland). 2020;10(14).
doi:10.3390/app10144792 .

Osmanović Omerdić, Ehlimana, Alagić-Džambić, Larisa, Krstić, Marko, Pašić-Kulenović, Maja, Odović, Jadranka, Vasiljević, Dragana, "In vitro dissolution study of acetylsalicylic acid and clopidogrel bisulfate solid dispersions: Validation of the RP-HPLC method for simultaneous analysis" in Applied Sciences (Switzerland), 10, no. 14 (2020),
https://doi.org/10.3390/app10144792 . .

TY  - JOUR
AU  - Krstić, Marko
AU  - Maksimović, Zoran
AU  - Ibrić, Svetlana
AU  - Bakić, Tamara
AU  - Prodanović, Jovana
AU  - Ražić, Slavica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3137
AB  - In this paper, agricultural waste (corn stover and wheat straw) was used for isolation of microcrystalline cellulose (MCC). Lignocellulosic biomass is widely available and applying smart technologies to valorise it will have a double benefit through environmental protection and achieving high-performance materials for targeted applications. The obtained MCC showed excellent features in terms of purity, physical-chemical properties and safety, as well. The methods applied for characterizing the materials were as follows: FT-IR, SEM, ICP-AAE and IC. Then, tablets were made by the compression method, using the isolated and purified MCC, as well as its commercially available counterpart. Excellent technological characteristics were confirmed by testing material compaction, compactibility, compressibility and drug release. This was one of the first tests in which Gamlen Tableting D was applied, especially in the case of using biomass, in the first phase, with prospects of application at a large scale, particularly, in the pharmaceutical industry.
PB  - Editura Acad Romane, Bucuresti
T2  - Cellulose Chemistry and Technology
T1  - Lignocellulosic biomass as a source of microcrystalline cellulose - chemical and technological characterization and future perspectives
VL  - 52
IS  - 7-8
SP  - 577
EP  - 588
UR  - https://hdl.handle.net/21.15107/rcub_farfar_3137
ER  - 

@article{
author = "Krstić, Marko and Maksimović, Zoran and Ibrić, Svetlana and Bakić, Tamara and Prodanović, Jovana and Ražić, Slavica",
year = "2018",
abstract = "In this paper, agricultural waste (corn stover and wheat straw) was used for isolation of microcrystalline cellulose (MCC). Lignocellulosic biomass is widely available and applying smart technologies to valorise it will have a double benefit through environmental protection and achieving high-performance materials for targeted applications. The obtained MCC showed excellent features in terms of purity, physical-chemical properties and safety, as well. The methods applied for characterizing the materials were as follows: FT-IR, SEM, ICP-AAE and IC. Then, tablets were made by the compression method, using the isolated and purified MCC, as well as its commercially available counterpart. Excellent technological characteristics were confirmed by testing material compaction, compactibility, compressibility and drug release. This was one of the first tests in which Gamlen Tableting D was applied, especially in the case of using biomass, in the first phase, with prospects of application at a large scale, particularly, in the pharmaceutical industry.",
publisher = "Editura Acad Romane, Bucuresti",
journal = "Cellulose Chemistry and Technology",
title = "Lignocellulosic biomass as a source of microcrystalline cellulose - chemical and technological characterization and future perspectives",
volume = "52",
number = "7-8",
pages = "577-588",
url = "https://hdl.handle.net/21.15107/rcub_farfar_3137"
}

Krstić, M., Maksimović, Z., Ibrić, S., Bakić, T., Prodanović, J.,& Ražić, S.. (2018). Lignocellulosic biomass as a source of microcrystalline cellulose - chemical and technological characterization and future perspectives. in Cellulose Chemistry and Technology
Editura Acad Romane, Bucuresti., 52(7-8), 577-588.
https://hdl.handle.net/21.15107/rcub_farfar_3137

Krstić M, Maksimović Z, Ibrić S, Bakić T, Prodanović J, Ražić S. Lignocellulosic biomass as a source of microcrystalline cellulose - chemical and technological characterization and future perspectives. in Cellulose Chemistry and Technology. 2018;52(7-8):577-588.
https://hdl.handle.net/21.15107/rcub_farfar_3137 .

Krstić, Marko, Maksimović, Zoran, Ibrić, Svetlana, Bakić, Tamara, Prodanović, Jovana, Ražić, Slavica, "Lignocellulosic biomass as a source of microcrystalline cellulose - chemical and technological characterization and future perspectives" in Cellulose Chemistry and Technology, 52, no. 7-8 (2018):577-588,
https://hdl.handle.net/21.15107/rcub_farfar_3137 .

TY  - JOUR
AU  - Krstić, Marko
AU  - Ražić, Slavica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3046
AB  - A large variety of analytical techniques are available to meet the needs of characterization of solid samples. But, when solid drug delivery systems are concerned we are faced with demanding methodologies which have to compile capabilities of analytical techniques in regard to large diversity of structures and surface functionality of analyzed adsorbent carriers. In this review, the most commonly used analytical techniques are presented with their basic principles, advantages and disadvantages in applications of interest. Adsorbent carriers are widely used today as ingredients in the formulation of pharmaceutical forms, for increasing the dissolution rate of the drug and hence the bioavailability. They are also used in the formulation of substances with modified or target drug release into a specific tissue. Methods of thermal analysis (Thermogravimetry - TGA, Differential Scanning Calorimetry - DSC and Thermal microscopy - TM), spectroscopic methods (Infrared Spectroscopy - IR, especially Fourier Transform Infrared Spectroscopy - FTIR and Raman spectroscopy), crystallographic methods (Powder X-Ray Diffraction - PXRD) and finally Scanning Electron Microscopy (SEM) are the most powerful in the characterization of modern therapeutic systems with porous adsorbents. The problem-solving power of each particular analytical method is often enhanced by using simultaneous methods rather than a single technique.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Medicinal Chemistry
T1  - Analytical Approaches to the Characterization of Solid Drug Delivery Systems with Porous Adsorbent Carriers
VL  - 25
IS  - 33
SP  - 3956
EP  - 3972
DO  - 10.2174/0929867325666180212120908
ER  - 

@article{
author = "Krstić, Marko and Ražić, Slavica",
year = "2018",
abstract = "A large variety of analytical techniques are available to meet the needs of characterization of solid samples. But, when solid drug delivery systems are concerned we are faced with demanding methodologies which have to compile capabilities of analytical techniques in regard to large diversity of structures and surface functionality of analyzed adsorbent carriers. In this review, the most commonly used analytical techniques are presented with their basic principles, advantages and disadvantages in applications of interest. Adsorbent carriers are widely used today as ingredients in the formulation of pharmaceutical forms, for increasing the dissolution rate of the drug and hence the bioavailability. They are also used in the formulation of substances with modified or target drug release into a specific tissue. Methods of thermal analysis (Thermogravimetry - TGA, Differential Scanning Calorimetry - DSC and Thermal microscopy - TM), spectroscopic methods (Infrared Spectroscopy - IR, especially Fourier Transform Infrared Spectroscopy - FTIR and Raman spectroscopy), crystallographic methods (Powder X-Ray Diffraction - PXRD) and finally Scanning Electron Microscopy (SEM) are the most powerful in the characterization of modern therapeutic systems with porous adsorbents. The problem-solving power of each particular analytical method is often enhanced by using simultaneous methods rather than a single technique.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Medicinal Chemistry",
title = "Analytical Approaches to the Characterization of Solid Drug Delivery Systems with Porous Adsorbent Carriers",
volume = "25",
number = "33",
pages = "3956-3972",
doi = "10.2174/0929867325666180212120908"
}

Krstić, M.,& Ražić, S.. (2018). Analytical Approaches to the Characterization of Solid Drug Delivery Systems with Porous Adsorbent Carriers. in Current Medicinal Chemistry
Bentham Science Publ Ltd, Sharjah., 25(33), 3956-3972.
https://doi.org/10.2174/0929867325666180212120908

Krstić M, Ražić S. Analytical Approaches to the Characterization of Solid Drug Delivery Systems with Porous Adsorbent Carriers. in Current Medicinal Chemistry. 2018;25(33):3956-3972.
doi:10.2174/0929867325666180212120908 .

Krstić, Marko, Ražić, Slavica, "Analytical Approaches to the Characterization of Solid Drug Delivery Systems with Porous Adsorbent Carriers" in Current Medicinal Chemistry, 25, no. 33 (2018):3956-3972,
https://doi.org/10.2174/0929867325666180212120908 . .

TY  - JOUR
AU  - Vojinović, Tanja
AU  - Medarević, Đorđe
AU  - Vranić, Edina
AU  - Potpara, Zorica
AU  - Krstić, Marko
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3243
AB  - In this study solid dispersions of carbamazepine in the hydrophilic Kollidon (R) VA64 polymer, adsorbed onto Neusilin (R) UFL2 adsorption carrier have been employed to improve carbamazepine dissolution rate. In order to evaluate effects of changing in the proportions of all solid dispersion components on carbamazepine dissolution rate, D-optimal mixture experimental design was used in the formulation development. From all prepared solid dispersion formulations, significantly faster carbamazepine dissolution was observed compared to pure drug. Ternary solid dispersions containing carbamazepine, Kollidon (R) VA64 and Neusilin (R) UFL2 showed superior dissolution performances over binary ones, containing only carbamazepine and Neusilin (R) UFL2. Proportion of Kollidon (R) VA64 showed the most profound effect on the amount of carbamazepine dissolved after 10 and 30 min, whereby these parameters increase upon increasing in Kollidon (R) VA64 concentrations up to the middle values in the studied range of Kollidon (R) VA64 concentrations. Physicochemical characterization of the selected samples using differential scanning calorimetry, FT-IR spectroscopy, powder X-ray diffraction and polarizing light microscopy showed polymorphic transition of carbamazepine from more thermodynamically stable monoclinic form (form III) to less thermodynamically stable triclinic form (form I) in the case of ternary, but not of binary solid dispersion formulations. This polymorphic transition can be one of the factors responsible for improving of carbamazepine dissolution rate from studied solid dispersions. Ternary solid dispersions prepared with Kollidon (R) VA64 hydrophilic polymer and Neusilin (R) UFL2 adsorption carrier resulted in significantly improvement of carbamazepine dissolution rate, but formation of metastable polymorphic form of carbamazepine requires particular care to be taken in ensuring product long term stability.
PB  - Elsevier Science BV, Amsterdam
T2  - Science of the Total Environment
T1  - Development of ternary solid dispersions with hydrophilic polymer and surface adsorbent for improving dissolution rate of carbamazepine
VL  - 26
IS  - 5
SP  - 725
EP  - 732
DO  - 10.1016/j.jsps.2018.02.017
ER  - 

@article{
author = "Vojinović, Tanja and Medarević, Đorđe and Vranić, Edina and Potpara, Zorica and Krstić, Marko and Đuriš, Jelena and Ibrić, Svetlana",
year = "2018",
abstract = "In this study solid dispersions of carbamazepine in the hydrophilic Kollidon (R) VA64 polymer, adsorbed onto Neusilin (R) UFL2 adsorption carrier have been employed to improve carbamazepine dissolution rate. In order to evaluate effects of changing in the proportions of all solid dispersion components on carbamazepine dissolution rate, D-optimal mixture experimental design was used in the formulation development. From all prepared solid dispersion formulations, significantly faster carbamazepine dissolution was observed compared to pure drug. Ternary solid dispersions containing carbamazepine, Kollidon (R) VA64 and Neusilin (R) UFL2 showed superior dissolution performances over binary ones, containing only carbamazepine and Neusilin (R) UFL2. Proportion of Kollidon (R) VA64 showed the most profound effect on the amount of carbamazepine dissolved after 10 and 30 min, whereby these parameters increase upon increasing in Kollidon (R) VA64 concentrations up to the middle values in the studied range of Kollidon (R) VA64 concentrations. Physicochemical characterization of the selected samples using differential scanning calorimetry, FT-IR spectroscopy, powder X-ray diffraction and polarizing light microscopy showed polymorphic transition of carbamazepine from more thermodynamically stable monoclinic form (form III) to less thermodynamically stable triclinic form (form I) in the case of ternary, but not of binary solid dispersion formulations. This polymorphic transition can be one of the factors responsible for improving of carbamazepine dissolution rate from studied solid dispersions. Ternary solid dispersions prepared with Kollidon (R) VA64 hydrophilic polymer and Neusilin (R) UFL2 adsorption carrier resulted in significantly improvement of carbamazepine dissolution rate, but formation of metastable polymorphic form of carbamazepine requires particular care to be taken in ensuring product long term stability.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Science of the Total Environment",
title = "Development of ternary solid dispersions with hydrophilic polymer and surface adsorbent for improving dissolution rate of carbamazepine",
volume = "26",
number = "5",
pages = "725-732",
doi = "10.1016/j.jsps.2018.02.017"
}

Vojinović, T., Medarević, Đ., Vranić, E., Potpara, Z., Krstić, M., Đuriš, J.,& Ibrić, S.. (2018). Development of ternary solid dispersions with hydrophilic polymer and surface adsorbent for improving dissolution rate of carbamazepine. in Science of the Total Environment
Elsevier Science BV, Amsterdam., 26(5), 725-732.
https://doi.org/10.1016/j.jsps.2018.02.017

Vojinović T, Medarević Đ, Vranić E, Potpara Z, Krstić M, Đuriš J, Ibrić S. Development of ternary solid dispersions with hydrophilic polymer and surface adsorbent for improving dissolution rate of carbamazepine. in Science of the Total Environment. 2018;26(5):725-732.
doi:10.1016/j.jsps.2018.02.017 .

Vojinović, Tanja, Medarević, Đorđe, Vranić, Edina, Potpara, Zorica, Krstić, Marko, Đuriš, Jelena, Ibrić, Svetlana, "Development of ternary solid dispersions with hydrophilic polymer and surface adsorbent for improving dissolution rate of carbamazepine" in Science of the Total Environment, 26, no. 5 (2018):725-732,
https://doi.org/10.1016/j.jsps.2018.02.017 . .

TY  - JOUR
AU  - Krstić, Marko
AU  - Lukić, I
AU  - Bušatlić, A
AU  - Lazarević, N
AU  - Vasiljević, Dragana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3130
AB  - Solid dispersions are defined as dispersions of one or more active pharmaceutical ingredients in inert solid-state carriers. They are made with the aim to increase solubility and the dissolution rate of low solubility active pharmaceutical ingredients, with the subsequent increase in their bioavailability. The aim of this study was the development and optimization of solid dispersion formulations with carbamazepine, using D-optimal experimental design, in order to increase the dissolution rate of the selected model drug. By using the method of experimental mixture design, solid dispersions were formulated by varying the ratio of carbamazepine (30-50 %), Gelucire® 44/14 (20-40 %) and Soluplus® polymer (30-50 %) (input parameters). Sixteen formulations were made and used for in vitro testing of the carbamazepine dissolution rate. The observed output parameters were the percentages of carbamazepine released after 10, 20, 30, 45, and 60 minutes. After the data analysis, three test formulations were chosen from different parts of the optimization area. They were prepared and the carbamazepine dissolution rate was determined, followed by stability assessment for 24 months under ambient conditions (25 °C, 40 % RH). The highest dissolution rate of carbamazepine from solid dispersions (more than 80 % in 30 minutes) was achieved at the carbamazepine mass fraction of about 40 %, Soluplus® of about 45 % and Gelucire® 44/14 of about 25 %. Comparing the predicted and the experimental obtained release rate profiles of carbamazepine from the three prepared optimized formulations, a significant compliance of the results was observed (f1<15; f2 >50). The application of the PAMPA (Parallel Artificial-Membrane Permeability Assay) test has shown that carbamazepine premeability was maintained and mildly increased in two out of the three tested optimzed solid state formulations. Raman spectroscopy, FT-IR and DSC analyes showed that in the three optimized solid dispersions, after preparation and 24 months of storage, interactions between carbamazepine and the excipients were not present and that carbamazepine remained in the single pharmacologically active crystal polymorph form III. Proper selection of solid dispersion proportions of carbamazepine, Gelucire® 44/14 and Soluplus® may significantly increase the dissolution rate of the active substance, and the method of experimental mixture design can be successfully used for optimization of these formulations.
PB  - Savez hemijskih inženjera, Beograd
T2  - Hemijska industrija
T1  - Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability
T1  - Čvrste disperzije sa karbamazepinom: Optimizacija formulacija, karakterizacija i ispitivanje dugoročne stabilnosti
VL  - 72
IS  - 4
SP  - 191
EP  - 204
DO  - 10.2298/HEMIND171025013K
ER  - 

@article{
author = "Krstić, Marko and Lukić, I and Bušatlić, A and Lazarević, N and Vasiljević, Dragana",
year = "2018",
abstract = "Solid dispersions are defined as dispersions of one or more active pharmaceutical ingredients in inert solid-state carriers. They are made with the aim to increase solubility and the dissolution rate of low solubility active pharmaceutical ingredients, with the subsequent increase in their bioavailability. The aim of this study was the development and optimization of solid dispersion formulations with carbamazepine, using D-optimal experimental design, in order to increase the dissolution rate of the selected model drug. By using the method of experimental mixture design, solid dispersions were formulated by varying the ratio of carbamazepine (30-50 %), Gelucire® 44/14 (20-40 %) and Soluplus® polymer (30-50 %) (input parameters). Sixteen formulations were made and used for in vitro testing of the carbamazepine dissolution rate. The observed output parameters were the percentages of carbamazepine released after 10, 20, 30, 45, and 60 minutes. After the data analysis, three test formulations were chosen from different parts of the optimization area. They were prepared and the carbamazepine dissolution rate was determined, followed by stability assessment for 24 months under ambient conditions (25 °C, 40 % RH). The highest dissolution rate of carbamazepine from solid dispersions (more than 80 % in 30 minutes) was achieved at the carbamazepine mass fraction of about 40 %, Soluplus® of about 45 % and Gelucire® 44/14 of about 25 %. Comparing the predicted and the experimental obtained release rate profiles of carbamazepine from the three prepared optimized formulations, a significant compliance of the results was observed (f1<15; f2 >50). The application of the PAMPA (Parallel Artificial-Membrane Permeability Assay) test has shown that carbamazepine premeability was maintained and mildly increased in two out of the three tested optimzed solid state formulations. Raman spectroscopy, FT-IR and DSC analyes showed that in the three optimized solid dispersions, after preparation and 24 months of storage, interactions between carbamazepine and the excipients were not present and that carbamazepine remained in the single pharmacologically active crystal polymorph form III. Proper selection of solid dispersion proportions of carbamazepine, Gelucire® 44/14 and Soluplus® may significantly increase the dissolution rate of the active substance, and the method of experimental mixture design can be successfully used for optimization of these formulations.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "Hemijska industrija",
title = "Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability, Čvrste disperzije sa karbamazepinom: Optimizacija formulacija, karakterizacija i ispitivanje dugoročne stabilnosti",
volume = "72",
number = "4",
pages = "191-204",
doi = "10.2298/HEMIND171025013K"
}

Krstić, M., Lukić, I., Bušatlić, A., Lazarević, N.,& Vasiljević, D.. (2018). Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability. in Hemijska industrija
Savez hemijskih inženjera, Beograd., 72(4), 191-204.
https://doi.org/10.2298/HEMIND171025013K

Krstić M, Lukić I, Bušatlić A, Lazarević N, Vasiljević D. Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability. in Hemijska industrija. 2018;72(4):191-204.
doi:10.2298/HEMIND171025013K .

Krstić, Marko, Lukić, I, Bušatlić, A, Lazarević, N, Vasiljević, Dragana, "Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability" in Hemijska industrija, 72, no. 4 (2018):191-204,
https://doi.org/10.2298/HEMIND171025013K . .

TY  - JOUR
AU  - Krstić, Marko
AU  - Đuriš, Jelena
AU  - Petrović, Ognjen
AU  - Lazarević, Nenad
AU  - Cvijić, Sandra
AU  - Ibrić, Svetlana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2995
AB  - The aim was to develop immediate-release carbamazepine lipid matrix tablets by using the melt granulation technique, application of Quality by design. The first set of screening experiments investigated the influence of six parameters (meltable binder type; amounts of meltable binder, carbamazepine and crospovidone; carrier type, and compression force) on carbamazepine release rate from tablets, using fractional factorial experimental design. In the second set of experiments, amounts of meltable binder and Cremophor (R) RH40 were varied according to the central composite design. The optimal formulation which showed the fastest release rate (more than 80% in first 30 min) was identified (compression force of 8 kN, 20% of Labrafil (R) 2130CS, 10% of Cremophor (R) RH40, 30% of carbamazepine, 5% of crospovidone NP and Neusilin (R) UFL2 used as the carrier). Different analytical techniques (DSC, PXRD, FT-IR, Raman spectroscopy) confirmed the maintenance of carbamazepine in its therapeutically active polymorph form III in the optimal formulation. Raman spectroscopy was used to demonstrate the stability of the optimal formulation during the two months stability study (25 degrees C, RH 40%). It can be concluded that melt granulation technique can be used in development of lipid matrix tablets with immediate-release of the drug.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Drug Delivery Science and Technology
T1  - Application of the melt granulation technique in development of lipid matrix tablets with immediate release of carbamazepine
VL  - 39
SP  - 467
EP  - 474
DO  - 10.1016/j.jddst.2017.04.024
ER  - 

@article{
author = "Krstić, Marko and Đuriš, Jelena and Petrović, Ognjen and Lazarević, Nenad and Cvijić, Sandra and Ibrić, Svetlana",
year = "2017",
abstract = "The aim was to develop immediate-release carbamazepine lipid matrix tablets by using the melt granulation technique, application of Quality by design. The first set of screening experiments investigated the influence of six parameters (meltable binder type; amounts of meltable binder, carbamazepine and crospovidone; carrier type, and compression force) on carbamazepine release rate from tablets, using fractional factorial experimental design. In the second set of experiments, amounts of meltable binder and Cremophor (R) RH40 were varied according to the central composite design. The optimal formulation which showed the fastest release rate (more than 80% in first 30 min) was identified (compression force of 8 kN, 20% of Labrafil (R) 2130CS, 10% of Cremophor (R) RH40, 30% of carbamazepine, 5% of crospovidone NP and Neusilin (R) UFL2 used as the carrier). Different analytical techniques (DSC, PXRD, FT-IR, Raman spectroscopy) confirmed the maintenance of carbamazepine in its therapeutically active polymorph form III in the optimal formulation. Raman spectroscopy was used to demonstrate the stability of the optimal formulation during the two months stability study (25 degrees C, RH 40%). It can be concluded that melt granulation technique can be used in development of lipid matrix tablets with immediate-release of the drug.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Drug Delivery Science and Technology",
title = "Application of the melt granulation technique in development of lipid matrix tablets with immediate release of carbamazepine",
volume = "39",
pages = "467-474",
doi = "10.1016/j.jddst.2017.04.024"
}

Krstić, M., Đuriš, J., Petrović, O., Lazarević, N., Cvijić, S.,& Ibrić, S.. (2017). Application of the melt granulation technique in development of lipid matrix tablets with immediate release of carbamazepine. in Journal of Drug Delivery Science and Technology
Elsevier Science BV, Amsterdam., 39, 467-474.
https://doi.org/10.1016/j.jddst.2017.04.024

Krstić M, Đuriš J, Petrović O, Lazarević N, Cvijić S, Ibrić S. Application of the melt granulation technique in development of lipid matrix tablets with immediate release of carbamazepine. in Journal of Drug Delivery Science and Technology. 2017;39:467-474.
doi:10.1016/j.jddst.2017.04.024 .

Krstić, Marko, Đuriš, Jelena, Petrović, Ognjen, Lazarević, Nenad, Cvijić, Sandra, Ibrić, Svetlana, "Application of the melt granulation technique in development of lipid matrix tablets with immediate release of carbamazepine" in Journal of Drug Delivery Science and Technology, 39 (2017):467-474,
https://doi.org/10.1016/j.jddst.2017.04.024 . .

TY  - JOUR
AU  - Krstić, Marko
AU  - Radojević, Marija
AU  - Stojanović, Dušica
AU  - Radojević, Vesna
AU  - Uskoković, Petar
AU  - Ibrić, Svetlana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3749
AB  - The preparation and characterization of films and nanofibers with carvedilol as a poorly water-soluble drug in poly (ethylene oxide) (PEO) polymer were investigated. Films are prepared by solution casting method, and nanofibers by electrospinning from a polymer solution. Water and mixture of ethanol and water were used as solvents. FT-IR analysis of the samples showed that there was no interaction between the polymer and the drug substance. DSC analysis revealed that carvedilol was dissolved in the polymer and influenced the degree of crystallinity of PEO. Carvedilol release rate for all of the formulations was increased in comparison with pure carvedilol. Significant differences in the rate of release of carvedilol from the films and nanofibers were observed. Field Emission Scanning Electron Microscope (FESEM) images of the obtained fiber was revealed the dependence of the fiber diameter of formulation and electrospinning process parameters, and consequently influence the amount and distribution of carvedilol in the encapsulated fibers.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method
VL  - 101
SP  - 160
EP  - 166
DO  - 10.1016/j.ejps.2017.02.006
ER  - 

@article{
author = "Krstić, Marko and Radojević, Marija and Stojanović, Dušica and Radojević, Vesna and Uskoković, Petar and Ibrić, Svetlana",
year = "2017",
abstract = "The preparation and characterization of films and nanofibers with carvedilol as a poorly water-soluble drug in poly (ethylene oxide) (PEO) polymer were investigated. Films are prepared by solution casting method, and nanofibers by electrospinning from a polymer solution. Water and mixture of ethanol and water were used as solvents. FT-IR analysis of the samples showed that there was no interaction between the polymer and the drug substance. DSC analysis revealed that carvedilol was dissolved in the polymer and influenced the degree of crystallinity of PEO. Carvedilol release rate for all of the formulations was increased in comparison with pure carvedilol. Significant differences in the rate of release of carvedilol from the films and nanofibers were observed. Field Emission Scanning Electron Microscope (FESEM) images of the obtained fiber was revealed the dependence of the fiber diameter of formulation and electrospinning process parameters, and consequently influence the amount and distribution of carvedilol in the encapsulated fibers.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method",
volume = "101",
pages = "160-166",
doi = "10.1016/j.ejps.2017.02.006"
}

Krstić, M., Radojević, M., Stojanović, D., Radojević, V., Uskoković, P.,& Ibrić, S.. (2017). Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 101, 160-166.
https://doi.org/10.1016/j.ejps.2017.02.006

Krstić M, Radojević M, Stojanović D, Radojević V, Uskoković P, Ibrić S. Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method. in European Journal of Pharmaceutical Sciences. 2017;101:160-166.
doi:10.1016/j.ejps.2017.02.006 .

Krstić, Marko, Radojević, Marija, Stojanović, Dušica, Radojević, Vesna, Uskoković, Petar, Ibrić, Svetlana, "Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method" in European Journal of Pharmaceutical Sciences, 101 (2017):160-166,
https://doi.org/10.1016/j.ejps.2017.02.006 . .

TY  - JOUR
AU  - Krstić, Marko
AU  - Radojević, Marija
AU  - Stojanović, Dušica
AU  - Radojević, Vesna
AU  - Uskoković, Petar
AU  - Ibrić, Svetlana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2930
AB  - The preparation and characterization of films and nanofibers with carvedilol as a poorly water-soluble drug in poly (ethylene oxide) (PEO) polymer were investigated. Films are prepared by solution casting method, and nanofibers by electrospinning from a polymer solution. Water and mixture of ethanol and water were used as solvents. FT-IR analysis of the samples showed that there was no interaction between the polymer and the drug substance. DSC analysis revealed that carvedilol was dissolved in the polymer and influenced the degree of crystallinity of PEO. Carvedilol release rate for all of the formulations was increased in comparison with pure carvedilol. Significant differences in the rate of release of carvedilol from the films and nanofibers were observed. Field Emission Scanning Electron Microscope (FESEM) images of the obtained fiber was revealed the dependence of the fiber diameter of formulation and electrospinning process parameters, and consequently influence the amount and distribution of carvedilol in the encapsulated fibers.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method
VL  - 101
SP  - 160
EP  - 166
DO  - 10.1016/j.ejps.2017.02.006
ER  - 

@article{
author = "Krstić, Marko and Radojević, Marija and Stojanović, Dušica and Radojević, Vesna and Uskoković, Petar and Ibrić, Svetlana",
year = "2017",
abstract = "The preparation and characterization of films and nanofibers with carvedilol as a poorly water-soluble drug in poly (ethylene oxide) (PEO) polymer were investigated. Films are prepared by solution casting method, and nanofibers by electrospinning from a polymer solution. Water and mixture of ethanol and water were used as solvents. FT-IR analysis of the samples showed that there was no interaction between the polymer and the drug substance. DSC analysis revealed that carvedilol was dissolved in the polymer and influenced the degree of crystallinity of PEO. Carvedilol release rate for all of the formulations was increased in comparison with pure carvedilol. Significant differences in the rate of release of carvedilol from the films and nanofibers were observed. Field Emission Scanning Electron Microscope (FESEM) images of the obtained fiber was revealed the dependence of the fiber diameter of formulation and electrospinning process parameters, and consequently influence the amount and distribution of carvedilol in the encapsulated fibers.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method",
volume = "101",
pages = "160-166",
doi = "10.1016/j.ejps.2017.02.006"
}

Krstić, M., Radojević, M., Stojanović, D., Radojević, V., Uskoković, P.,& Ibrić, S.. (2017). Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 101, 160-166.
https://doi.org/10.1016/j.ejps.2017.02.006

Krstić M, Radojević M, Stojanović D, Radojević V, Uskoković P, Ibrić S. Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method. in European Journal of Pharmaceutical Sciences. 2017;101:160-166.
doi:10.1016/j.ejps.2017.02.006 .

Krstić, Marko, Radojević, Marija, Stojanović, Dušica, Radojević, Vesna, Uskoković, Petar, Ibrić, Svetlana, "Formulation and characterization of nanofibers and films with carvedilol prepared by electrospinning and solution casting method" in European Journal of Pharmaceutical Sciences, 101 (2017):160-166,
https://doi.org/10.1016/j.ejps.2017.02.006 . .

TY  - JOUR
AU  - Trajković, Filip
AU  - Stošić, Igor
AU  - Krstić, Marko
AU  - Đogo-Mračević, Svetlana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2739
AB  - Water quality is defined by numerous physical, chemical and biological parameters, the content of organic and inorganic substances, and its monitoring has become a global health, economic and legal interest in recent decades. In this paper, some of the most important indicators of chemical surface water quality were determined in samples from the river Sava (Ada i Ušće), Danube (Pristanište i Kej) and Topčiderka (Rakovica). Water samples from selected locations were collected in November 2014 and chemical parameters were determined using standard analytical procedures. The results were obtained in the following range: pH (5.71-6.40), content of dissolved oxygen (11.04-11.99 mg/dm3), chloride (20.89-32.82 mg/dm3), alkalinity (207.9-300.9 mg CaCO3/dm3), acidity (31.79-54.90 mg CaCO3/dm3), calcium (37.23-54.90 mg/dm3), magnesium (6.90-23.65 mg/dm3), total water hardness (137.6-235.8 mg CaCO3/dm3), chemical oxygen demand - COD (4.08-9.12 mg O2 /dm3). Tested parameters indicate no significant pollution of the surface water, but in order to perform the correct categorization of water in these rivers, it would be necessary to do further testing of physical, chemical and biological indicators of the water quality.
AB  - Kvalitet vode je definisan velikim brojem fizičkih, hemijskih i bioloških parametara, kao i sadržajem organskih i neorganskih materija, a njegovo ispitivanje poslednjih decenija ima globalni zdravstveni, ekonomski i pravni interes. U ovom radu su određivani neki od najvažnijih pokazatelja hemijskog kvaliteta površinskih voda u uzorcima iz reke Save (Ada i Ušće), Dunava (Pristanište i Kej) i Topčiderke (Rakovica). Uzorci vode su skupljani u novembru 2014. god. i svi hemijski parametri su određivani standardnim analitičkim metodama. Dobijeni su sledeći rezultati: pH (5,71-6,40), sadržaj rastvorenog kiseonika (11,04-11,99 mg/dm3), hloridi (20,89-32,82 mg/dm3), alkalitet (207,9-300,9 mg CaCO3/ dm3), aciditet (31,79-54,90 mg CaCO3/dm3), kalcijum (37,23-54,90 mg/dm3), magnezijum (6,90-23,65 mg/dm3), ukupna tvrdoća vode (137,6-235,8 mg CaCO3/dm3), hemijska potrošnja kiseonika - HPK (4,08-9,12 mg O2/dm3). Ispitivani parametri ne ukazuju na značajno zagađenje površinskih voda. Da bi se izvršila ispravna kategorizacija vode u ovim rekama, potrebno bi bilo uraditi dodatna ispitivanja pokazatelja vezanih za fizički, hemijski i biološki kvalitet.
PB  - Univerzitet u Beogradu - Medicinski fakultet, Beograd
T2  - Medicinski podmladak
T1  - Determination of chemical quality parameters in surface water samples from rivers Sava, Danube, and Topčiderka
T1  - Određivanje hemijskih pokazatelja kvaliteta površinskih voda u uzorcima Save, Dunava i Topčiderske reke
VL  - 67
IS  - 3
SP  - 81
EP  - 87
DO  - 10.5937/mp67-12781
ER  - 

@article{
author = "Trajković, Filip and Stošić, Igor and Krstić, Marko and Đogo-Mračević, Svetlana",
year = "2016",
abstract = "Water quality is defined by numerous physical, chemical and biological parameters, the content of organic and inorganic substances, and its monitoring has become a global health, economic and legal interest in recent decades. In this paper, some of the most important indicators of chemical surface water quality were determined in samples from the river Sava (Ada i Ušće), Danube (Pristanište i Kej) and Topčiderka (Rakovica). Water samples from selected locations were collected in November 2014 and chemical parameters were determined using standard analytical procedures. The results were obtained in the following range: pH (5.71-6.40), content of dissolved oxygen (11.04-11.99 mg/dm3), chloride (20.89-32.82 mg/dm3), alkalinity (207.9-300.9 mg CaCO3/dm3), acidity (31.79-54.90 mg CaCO3/dm3), calcium (37.23-54.90 mg/dm3), magnesium (6.90-23.65 mg/dm3), total water hardness (137.6-235.8 mg CaCO3/dm3), chemical oxygen demand - COD (4.08-9.12 mg O2 /dm3). Tested parameters indicate no significant pollution of the surface water, but in order to perform the correct categorization of water in these rivers, it would be necessary to do further testing of physical, chemical and biological indicators of the water quality., Kvalitet vode je definisan velikim brojem fizičkih, hemijskih i bioloških parametara, kao i sadržajem organskih i neorganskih materija, a njegovo ispitivanje poslednjih decenija ima globalni zdravstveni, ekonomski i pravni interes. U ovom radu su određivani neki od najvažnijih pokazatelja hemijskog kvaliteta površinskih voda u uzorcima iz reke Save (Ada i Ušće), Dunava (Pristanište i Kej) i Topčiderke (Rakovica). Uzorci vode su skupljani u novembru 2014. god. i svi hemijski parametri su određivani standardnim analitičkim metodama. Dobijeni su sledeći rezultati: pH (5,71-6,40), sadržaj rastvorenog kiseonika (11,04-11,99 mg/dm3), hloridi (20,89-32,82 mg/dm3), alkalitet (207,9-300,9 mg CaCO3/ dm3), aciditet (31,79-54,90 mg CaCO3/dm3), kalcijum (37,23-54,90 mg/dm3), magnezijum (6,90-23,65 mg/dm3), ukupna tvrdoća vode (137,6-235,8 mg CaCO3/dm3), hemijska potrošnja kiseonika - HPK (4,08-9,12 mg O2/dm3). Ispitivani parametri ne ukazuju na značajno zagađenje površinskih voda. Da bi se izvršila ispravna kategorizacija vode u ovim rekama, potrebno bi bilo uraditi dodatna ispitivanja pokazatelja vezanih za fizički, hemijski i biološki kvalitet.",
publisher = "Univerzitet u Beogradu - Medicinski fakultet, Beograd",
journal = "Medicinski podmladak",
title = "Determination of chemical quality parameters in surface water samples from rivers Sava, Danube, and Topčiderka, Određivanje hemijskih pokazatelja kvaliteta površinskih voda u uzorcima Save, Dunava i Topčiderske reke",
volume = "67",
number = "3",
pages = "81-87",
doi = "10.5937/mp67-12781"
}

Trajković, F., Stošić, I., Krstić, M.,& Đogo-Mračević, S.. (2016). Determination of chemical quality parameters in surface water samples from rivers Sava, Danube, and Topčiderka. in Medicinski podmladak
Univerzitet u Beogradu - Medicinski fakultet, Beograd., 67(3), 81-87.
https://doi.org/10.5937/mp67-12781

Trajković F, Stošić I, Krstić M, Đogo-Mračević S. Determination of chemical quality parameters in surface water samples from rivers Sava, Danube, and Topčiderka. in Medicinski podmladak. 2016;67(3):81-87.
doi:10.5937/mp67-12781 .

Trajković, Filip, Stošić, Igor, Krstić, Marko, Đogo-Mračević, Svetlana, "Determination of chemical quality parameters in surface water samples from rivers Sava, Danube, and Topčiderka" in Medicinski podmladak, 67, no. 3 (2016):81-87,
https://doi.org/10.5937/mp67-12781 . .

TY  - JOUR
AU  - Krstić, Marko
AU  - Ibrić, Svetlana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2618
AB  - One of the problems with orally used drugs is their poor solubility, which can be overcome by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). The aim is to choose the appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol (R) (1: 1)) and cosurfactant (Transcutol (R) HP) are formed by applying mixture design. 16 formulations were formulated, where the proportion of lipids, surfactant and cosurfactant were varied (input parameters) in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water), the droplet size and polydispersity index (PdI) of the obtained emulsions (output parameters) were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that describe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin (R) UFl2, Neusilin (R) FL2, Sylysia (R) 320 and diatomite were used as the carriers. The ratio of SNEDDS: carrier was 1: 1 or 2: 1. Dissolution testing was carried out in the rotation paddles apparatus. Characterization of solid SNEDDS was performed using the hot stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectrophotometry with Fourier transformation (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (PXRD). Selected SNEDDS consisting of lipids (21.12%), surfactant (42.24%) and cosurfactant (36.64%) had a droplet size 157.02 +/- 34.09 nm and PdI 0.184 +/- 0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia (R) 320). It can be concluded that in all formulations carbamazepine is present in the thermodynamically most stable polymorphic form III. Formulation of solid SNEDDS can significantly increase dissolution rate of carbamazepine, with conservation of the polymorphic form III CBZ and potentially increased bioavailability.
PB  - Savez hemijskih inženjera, Beograd
T2  - Hemijska industrija
T1  - Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist
VL  - 70
IS  - 5
SP  - 525
EP  - 537
DO  - 10.2298/HEMIND150623059K
ER  - 

@article{
author = "Krstić, Marko and Ibrić, Svetlana",
year = "2016",
abstract = "One of the problems with orally used drugs is their poor solubility, which can be overcome by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). The aim is to choose the appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol (R) (1: 1)) and cosurfactant (Transcutol (R) HP) are formed by applying mixture design. 16 formulations were formulated, where the proportion of lipids, surfactant and cosurfactant were varied (input parameters) in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water), the droplet size and polydispersity index (PdI) of the obtained emulsions (output parameters) were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that describe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin (R) UFl2, Neusilin (R) FL2, Sylysia (R) 320 and diatomite were used as the carriers. The ratio of SNEDDS: carrier was 1: 1 or 2: 1. Dissolution testing was carried out in the rotation paddles apparatus. Characterization of solid SNEDDS was performed using the hot stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectrophotometry with Fourier transformation (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (PXRD). Selected SNEDDS consisting of lipids (21.12%), surfactant (42.24%) and cosurfactant (36.64%) had a droplet size 157.02 +/- 34.09 nm and PdI 0.184 +/- 0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia (R) 320). It can be concluded that in all formulations carbamazepine is present in the thermodynamically most stable polymorphic form III. Formulation of solid SNEDDS can significantly increase dissolution rate of carbamazepine, with conservation of the polymorphic form III CBZ and potentially increased bioavailability.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "Hemijska industrija",
title = "Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist",
volume = "70",
number = "5",
pages = "525-537",
doi = "10.2298/HEMIND150623059K"
}

Krstić, M.,& Ibrić, S.. (2016). Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist. in Hemijska industrija
Savez hemijskih inženjera, Beograd., 70(5), 525-537.
https://doi.org/10.2298/HEMIND150623059K

Krstić M, Ibrić S. Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist. in Hemijska industrija. 2016;70(5):525-537.
doi:10.2298/HEMIND150623059K .

Krstić, Marko, Ibrić, Svetlana, "Application of mixture experimental design in formulation and characterization of solid selfnanoemulsifying drug delivery systems containing carbamazepine [Primena dizajna smeše u formulaciji i karakterizaciji čvrstih samo-nanoemulgujućih terapijskih sist" in Hemijska industrija, 70, no. 5 (2016):525-537,
https://doi.org/10.2298/HEMIND150623059K . .

TY  - JOUR
AU  - Krstić, Marko
AU  - Milović, Mladen
AU  - Ibrić, Svetlana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2701
AB  - In latest years, many natural and synthetic solid carriers attract increasing attention, due to theirs biocompatibility, acceptable ecological and toxicological properties, possible modification of physico-chemical properties, simple production, high stability and relatively low price. These carriers have similar chemical structure, mostly based on silicon-dioxide, magnesium aluminometasilicate and calcium phosphate, and differ from each other in structure porosity, specific surface area, size, volume and shape of pores, and possibility of surface functionalization. Ordered mesoporous materials like MCM - 41 and SBA - 15, as well as porous materials from Neusilin® and Sylysia® groups, represent the most common adsorbents evaluated in order to increase drug dissolution rate, and its bioavailability, and also in modifiedand targeted drug release formulations. Also, natural silica material, isolated from diatomites, diatom microshells, with its unique characteristics, represents relatively cheap solid carrier used in formulation of oral dosage forms and implants. Modern adsorbents are mostly used in formulations of solid dispersions with low water-soluble drugs, or as solid carriers for lipid formulations. In latest years, modern porous carriers are evaluated for possible surface functionalization in order to achieve prolonged or signal-initiated drug release.
AB  - Poslednjih godina veliki broj adsorpcionih nosača prirodnog i sintetskog porekla privlači sve više pažnje zbog svoje biokompatibilnosti, prihvatljivih ekoloških i toksikoloških osobina, velike mogućnosti za modifikaciju fizičkohemijskih osobina, jednostavnog dobijanja, visoke stabilnosti i relativno niske cene. Ovi nosači su slične hemijske strukture, najčešće na bazi silicijum-dioksida, magnezijum-aluminometasilikata i kalcijum-fosfata, a međusobno se razlikuju po poroznosti struktura, specifičnoj površini, veličini, zapremini i obliku pora kao i mogućnosti funkcionalizacije površine. Uređeni mezoporozni materijali kao što su MCM - 41 i SBA - 15, kao i porozni materijali iz grupe Neusilin®-a i Sylysia®-a predstavljaju najčešće ispitivane adsorbente sa ciljem da povećaju brzinu rastvaranja lekovite supstance, a samim tim i biološku raspoloživost, ali se koriste i u formulaciji preparata sa modifikovanim ili ciljanim oslobađanjem lekovite supstance u određeno tkivo. Takođe prirodni silika materijal jedinstvenih karakteristika, izolovan iz dijatomita, dijatomitne mikrokapsule, predstavlja relativno jeftin adsorbent za formulaciju nosača za peroralnu primenu lekovite supstance kao i primenu u obliku implanta. Savremeni adsorbenti najčešće se koriste u izradi čvrstih disperzija sa nisko rastvorljivom lekovitom supstancom, ili kao adsorbenti za različite lipidne formulacije. Jedna od mogućnosti primene savremenih nosača koja se poslednjih godina ispituje jeste i funkcionalizacija površine poroznih materijala u cilju postizanja usporenog ili signalinicirajućeg oslobađanja lekovite supstance.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Properties and potential application of modern adsorbents in formulation of solid drug delivery systems
T1  - Karakteristike i potencijalna primena savremenih adsorbenata u formulaciji nosača lekovitih supstanci
VL  - 66
IS  - 1
SP  - 1
EP  - 23
DO  - 10.5937/arhfarm1601001K
ER  - 

@article{
author = "Krstić, Marko and Milović, Mladen and Ibrić, Svetlana",
year = "2016",
abstract = "In latest years, many natural and synthetic solid carriers attract increasing attention, due to theirs biocompatibility, acceptable ecological and toxicological properties, possible modification of physico-chemical properties, simple production, high stability and relatively low price. These carriers have similar chemical structure, mostly based on silicon-dioxide, magnesium aluminometasilicate and calcium phosphate, and differ from each other in structure porosity, specific surface area, size, volume and shape of pores, and possibility of surface functionalization. Ordered mesoporous materials like MCM - 41 and SBA - 15, as well as porous materials from Neusilin® and Sylysia® groups, represent the most common adsorbents evaluated in order to increase drug dissolution rate, and its bioavailability, and also in modifiedand targeted drug release formulations. Also, natural silica material, isolated from diatomites, diatom microshells, with its unique characteristics, represents relatively cheap solid carrier used in formulation of oral dosage forms and implants. Modern adsorbents are mostly used in formulations of solid dispersions with low water-soluble drugs, or as solid carriers for lipid formulations. In latest years, modern porous carriers are evaluated for possible surface functionalization in order to achieve prolonged or signal-initiated drug release., Poslednjih godina veliki broj adsorpcionih nosača prirodnog i sintetskog porekla privlači sve više pažnje zbog svoje biokompatibilnosti, prihvatljivih ekoloških i toksikoloških osobina, velike mogućnosti za modifikaciju fizičkohemijskih osobina, jednostavnog dobijanja, visoke stabilnosti i relativno niske cene. Ovi nosači su slične hemijske strukture, najčešće na bazi silicijum-dioksida, magnezijum-aluminometasilikata i kalcijum-fosfata, a međusobno se razlikuju po poroznosti struktura, specifičnoj površini, veličini, zapremini i obliku pora kao i mogućnosti funkcionalizacije površine. Uređeni mezoporozni materijali kao što su MCM - 41 i SBA - 15, kao i porozni materijali iz grupe Neusilin®-a i Sylysia®-a predstavljaju najčešće ispitivane adsorbente sa ciljem da povećaju brzinu rastvaranja lekovite supstance, a samim tim i biološku raspoloživost, ali se koriste i u formulaciji preparata sa modifikovanim ili ciljanim oslobađanjem lekovite supstance u određeno tkivo. Takođe prirodni silika materijal jedinstvenih karakteristika, izolovan iz dijatomita, dijatomitne mikrokapsule, predstavlja relativno jeftin adsorbent za formulaciju nosača za peroralnu primenu lekovite supstance kao i primenu u obliku implanta. Savremeni adsorbenti najčešće se koriste u izradi čvrstih disperzija sa nisko rastvorljivom lekovitom supstancom, ili kao adsorbenti za različite lipidne formulacije. Jedna od mogućnosti primene savremenih nosača koja se poslednjih godina ispituje jeste i funkcionalizacija površine poroznih materijala u cilju postizanja usporenog ili signalinicirajućeg oslobađanja lekovite supstance.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Properties and potential application of modern adsorbents in formulation of solid drug delivery systems, Karakteristike i potencijalna primena savremenih adsorbenata u formulaciji nosača lekovitih supstanci",
volume = "66",
number = "1",
pages = "1-23",
doi = "10.5937/arhfarm1601001K"
}

Krstić, M., Milović, M.,& Ibrić, S.. (2016). Properties and potential application of modern adsorbents in formulation of solid drug delivery systems. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 66(1), 1-23.
https://doi.org/10.5937/arhfarm1601001K

Krstić M, Milović M, Ibrić S. Properties and potential application of modern adsorbents in formulation of solid drug delivery systems. in Arhiv za farmaciju. 2016;66(1):1-23.
doi:10.5937/arhfarm1601001K .

Krstić, Marko, Milović, Mladen, Ibrić, Svetlana, "Properties and potential application of modern adsorbents in formulation of solid drug delivery systems" in Arhiv za farmaciju, 66, no. 1 (2016):1-23,
https://doi.org/10.5937/arhfarm1601001K . .

TY  - THES
AU  - Krstić, Marko
PY  - 2015
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=2311
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:10217/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=47495695
UR  - http://nardus.mpn.gov.rs/123456789/4239
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3393
AB  - Poslednjih godina sve veći broj novosintetisanih lekovitih supstanci su nisko rastvorljive u vodi. Jedan od načina za povećanje brzine rastvaranja/rastvorljivosti lekovitih supstanci jeste formulacija čvrstih samo-dispergujućih sistema.Sveobuhvatni cilj ove doktorske disertacije jeste formulacija, izrada i karakterizacija čvrstih samo-dispergujućih sistema sa karbamazepinom, uz korišćenje prirodnih i sintetskih adsorpcionih nosača, radi povećanja brzine rastvaranja i permeabilnosti karbamazepina.U prvoj fazi istraživanja izvršen je odabir tečnih samo-dispergujućih sistema, različitog stepena disperziteta, za različite kombinacije ulja/surfaktanta/kosurfaktanta (korastvarača). U prvom delu su, nakon metode titracije vodom, za sisteme trigliceridi srednje dužine lanaca/Polisorbat 80/Makrogol 400/voda i trigliceridi srednje dužine lanaca/Cremophor® EL/Makrogol 400/voda, konstruisani pseudo-ternerni fazni dijagrami. Odabran je tečni samo-mikroemulgujući nosač (SMEDDS) trigliceridi srednje dužine lanaca/Cremophor® EL/Makrogol 400 (10:66,75:22,25). U nastavku ove faze je na isti način odabran tečni samo-emulgujući nosač (SEDDS) trigliceridi srednje dužine lanaca/Polisorbat 80/Transcutol® HP (20:60:20). Primenom eksperimentalnog dizajna, dizajna smeše, odabran je tečni samo-nanoemulgujući nosač (SNEDDS) za kombinaciju trigliceridi srednje dužine lanaca/Polisorbat 80/Labrasol®/Transcutol® HP (21,21:21,12:21,12:36,64). U ovoj fazi je pokazano veliko slaganje između predviđenih i eksperimentalno dobijenih vrednosti za veličinu kapi i PdI.U drugoj fazi istraživanja izvršena je formulacija, izrada i karakterizacija čvrstih samo- dispergujućih nosača. U prvom delu, izrađene su binarne čvrste disperzije karbamazepina i adsorpcionih nosača (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320, dijatomiti), uz variranje odnosa karbamazepin/nosač 1:1, 1:2 i 1:6 i dve metode izrade, uparavanja etanola na sobnoj temperaturi i na 70 °C. Uočeno je da se formulacijom čvrstih disperzija sa Neusilin®-om UFL2, Neusilin®-om FL2 i Sylysia®-om 320, pri odnosima karbamazepin/nosač 1:2 i 1:6 postiže značajno povećanje brzine rastvaranja karbamazepina, dok je iz čvrstih disperzija sa karbamazepinom, pri odnosu 1:1 i u svim formulacijama sa dijatomitima brzina oslobađanja slična prašku karbamazepina. U svim formulacijama je došlo do prelaska karbamazepina u amorfni oblik ili u polimorfni oblik II. U nastavku ove faze pristupilo se formulaciji, izradi i karakterizaciji čvrstih samo-mikroemulgujućih sistema sa karbamazepinom (SSMEDDS), pri čemu je udeo karbamazepina bio stalan (20%), dok je odnos SMEDDS/nosač (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320 i dijatomiti) variran i iznosio je 1:1 ili 3:1. Formulacije su izrađene korišćenjem dve metode (metoda direktne аdsorpcije i metoda uparavanja). Uočeno je da metoda uparavanja, uz korišćenje etanola, nije pogodna zbog prelaska karbamazepina u polimorfni oblik II. Iz SSMEDDS postiže se značajno povećanje brzine rastvaranja (preko 90% za 30 minuta). Rezultati ispitivanja brzine rastvaranja karbamzapina iz izrađenih SSMEDDS pokazuju da se redosled brzine oslobađanja karbamazepina smanjuje redom korišćenjem sledećih nosača Neusilin® UFL2 > Sylysia® 320 > Neusilin® FL2 > dijаtomiti. Značajna razlika u brzini oslobađanja karbamazepina iz formulacija izrađenih sa različitim odnosima adsorpcioni nosač/SMEDDS nije uočena. Čvrsti samo-nanoemulgujući sistemi sa karbamazepinom (SSNEDDS) izrađen su metodom direktne adsorpcije, uz variranje odnosa SNEDDS/nosač (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320 i dijatomiti) 1:1 ili 2:1, pri čemu je udeo karbamazepina bio stalan (20%). Formulacija SSNEDDS iz koje je postignuto najbrže oslobađanjekarbamazepina sadrži jednak udeo SNEDDS-a i adsorpcionog nosača (Sylysia® 320), iz ove formulacije je za 30 minuta oslobođeno oko 90% karbamazepina...
AB  - In latest years, an increasing number of newly synthetized drugs have low solubility in water. Formulation of solid self-dispersing drug delivery systems is one of many approaches to increase the dissolution rate/solubility of these drugs.The overall aim of this doctoral dissertation is formulation, making and characterization of solid self-dispersing drug delivery systems with carbamazepine, using natural and synthetic solid carriers, in order to increase the dissolution rate and permeability of carbamazepine.In phase I of this research, proper selection of solid self-dispersing drug delivery systems, with different dispersity degree, for different oil/surfactant/cosurfactant (cosolvent) ratio was done. In the first part, after titration with water, pseudo-ternary phase diagrams were constructed for systems medium chain triglycerides/Polysorbate 80/Macrogol 400/water, and medium chain triglycerides/Cremophor® EL/Macrogol 400/water. Liquid self-emulsifying system (SEDDS) composed of medium chain triglycerides/Cremophor® EL/Macrogol 400, in a 10:66,75:22,25 ratio was selected. Furthermore, liquid self-nanoemulsifying system (SNEDDS) composed of medium chain triglycerides/Polysorbate 80/Transcutol® HP, in 20:60:20 ratio was also selected. Using mixture experimental design, liquid self-nanoemulsifying system (SNEDDS) composed of medium chain triglycerides/Polysorbate 80/Labrasol®/ Transcutol® HP, in 21,21:21,12:21,12:36,64 was selected. In this phase, a high matching between the predicted and the experimentally obtained values for droplet size and PdI was demonstrated.In phase II of the research, formulation, preparation and characterization of solid dispersing drug delivery systems were conducted. In its first stage, binary solid dispersions of carbamazepine and solid carriers (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320, diatomites) were prepared, varying the carbamazepine/carrier ratio (1:1, 1:2 and 1:6) and two formulation methods - evaporation of ethanol at room temperature, and at 70 °C. It was observed that solid dispersions made of Neusilin® UFL2, Neusilin® FL2 and Sylysia® 320, with carbamazepine/carrier ratios 1:2 and 1:6 leads to a significant increase in the dissolution rate of carbamazepine, whereas in formulations with a 1:1 carbamazepine/carrier ratio, and also in all formulations with diatomites, the dissolution rate of carbamazepine was similar to carbamazepine powder. In all formulations, carbamazepine was converted to the amorphous form or to polymorph form II. In the next stage of this phase, formulation, preparation and characterization of solid self-microemulsifying drug delivery systems with carbamazepine (SSMEDS) were done. The carbamazepine ratio was constant (20%), while the SMEDDS/carrier (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320, diatomites) ratio was varied (1:1 and 3:1). Formulations were made using two methods (direct adsorption and evaporation with ethanol (99,5% v/v)). It was noted that the ethanol formulation method is not adequate, because of the conversion of carbamazepine into polymorph form II. A significant increase in the dissolution rate of carbamazepine from SSMEDS occurred (more than 90% in 30 minutes). The results of the dissolution test show that the dissolution rate of carbamazepine from SSMEDS formulations decreases with use of Neusilin® UFL2, Sylysia® 320, Neusilin® FL2 and diatomites, respectively. A significant difference in dissolution rate of carbamazepine from formulations with different carbamazepine/carrier ratio was not observed. Solid self-nanoemulsifying drug delivery system with carbamazepine (SSNEDS) was made by direct adsorption method, whereby carbamazepine ratio was constant (20%), and the SNEDDS/carrier (Neusilin® UFL2,Neusilin® FL2, Sylysia® 320, diatomites) ratio was varied (1:1 and 2:1)...
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Formulacija i karakterizacija čvrstih samo-dispergujućih nosača karbamazepina izrađenih sa poroznim adsorbensima
T1  - Formulation and characterization of solid self-dispersing carriers of carbamazepine prepared with porous adsorbents
UR  - https://hdl.handle.net/21.15107/rcub_nardus_4239
ER  - 

@phdthesis{
author = "Krstić, Marko",
year = "2015",
abstract = "Poslednjih godina sve veći broj novosintetisanih lekovitih supstanci su nisko rastvorljive u vodi. Jedan od načina za povećanje brzine rastvaranja/rastvorljivosti lekovitih supstanci jeste formulacija čvrstih samo-dispergujućih sistema.Sveobuhvatni cilj ove doktorske disertacije jeste formulacija, izrada i karakterizacija čvrstih samo-dispergujućih sistema sa karbamazepinom, uz korišćenje prirodnih i sintetskih adsorpcionih nosača, radi povećanja brzine rastvaranja i permeabilnosti karbamazepina.U prvoj fazi istraživanja izvršen je odabir tečnih samo-dispergujućih sistema, različitog stepena disperziteta, za različite kombinacije ulja/surfaktanta/kosurfaktanta (korastvarača). U prvom delu su, nakon metode titracije vodom, za sisteme trigliceridi srednje dužine lanaca/Polisorbat 80/Makrogol 400/voda i trigliceridi srednje dužine lanaca/Cremophor® EL/Makrogol 400/voda, konstruisani pseudo-ternerni fazni dijagrami. Odabran je tečni samo-mikroemulgujući nosač (SMEDDS) trigliceridi srednje dužine lanaca/Cremophor® EL/Makrogol 400 (10:66,75:22,25). U nastavku ove faze je na isti način odabran tečni samo-emulgujući nosač (SEDDS) trigliceridi srednje dužine lanaca/Polisorbat 80/Transcutol® HP (20:60:20). Primenom eksperimentalnog dizajna, dizajna smeše, odabran je tečni samo-nanoemulgujući nosač (SNEDDS) za kombinaciju trigliceridi srednje dužine lanaca/Polisorbat 80/Labrasol®/Transcutol® HP (21,21:21,12:21,12:36,64). U ovoj fazi je pokazano veliko slaganje između predviđenih i eksperimentalno dobijenih vrednosti za veličinu kapi i PdI.U drugoj fazi istraživanja izvršena je formulacija, izrada i karakterizacija čvrstih samo- dispergujućih nosača. U prvom delu, izrađene su binarne čvrste disperzije karbamazepina i adsorpcionih nosača (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320, dijatomiti), uz variranje odnosa karbamazepin/nosač 1:1, 1:2 i 1:6 i dve metode izrade, uparavanja etanola na sobnoj temperaturi i na 70 °C. Uočeno je da se formulacijom čvrstih disperzija sa Neusilin®-om UFL2, Neusilin®-om FL2 i Sylysia®-om 320, pri odnosima karbamazepin/nosač 1:2 i 1:6 postiže značajno povećanje brzine rastvaranja karbamazepina, dok je iz čvrstih disperzija sa karbamazepinom, pri odnosu 1:1 i u svim formulacijama sa dijatomitima brzina oslobađanja slična prašku karbamazepina. U svim formulacijama je došlo do prelaska karbamazepina u amorfni oblik ili u polimorfni oblik II. U nastavku ove faze pristupilo se formulaciji, izradi i karakterizaciji čvrstih samo-mikroemulgujućih sistema sa karbamazepinom (SSMEDDS), pri čemu je udeo karbamazepina bio stalan (20%), dok je odnos SMEDDS/nosač (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320 i dijatomiti) variran i iznosio je 1:1 ili 3:1. Formulacije su izrađene korišćenjem dve metode (metoda direktne аdsorpcije i metoda uparavanja). Uočeno je da metoda uparavanja, uz korišćenje etanola, nije pogodna zbog prelaska karbamazepina u polimorfni oblik II. Iz SSMEDDS postiže se značajno povećanje brzine rastvaranja (preko 90% za 30 minuta). Rezultati ispitivanja brzine rastvaranja karbamzapina iz izrađenih SSMEDDS pokazuju da se redosled brzine oslobađanja karbamazepina smanjuje redom korišćenjem sledećih nosača Neusilin® UFL2 > Sylysia® 320 > Neusilin® FL2 > dijаtomiti. Značajna razlika u brzini oslobađanja karbamazepina iz formulacija izrađenih sa različitim odnosima adsorpcioni nosač/SMEDDS nije uočena. Čvrsti samo-nanoemulgujući sistemi sa karbamazepinom (SSNEDDS) izrađen su metodom direktne adsorpcije, uz variranje odnosa SNEDDS/nosač (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320 i dijatomiti) 1:1 ili 2:1, pri čemu je udeo karbamazepina bio stalan (20%). Formulacija SSNEDDS iz koje je postignuto najbrže oslobađanjekarbamazepina sadrži jednak udeo SNEDDS-a i adsorpcionog nosača (Sylysia® 320), iz ove formulacije je za 30 minuta oslobođeno oko 90% karbamazepina..., In latest years, an increasing number of newly synthetized drugs have low solubility in water. Formulation of solid self-dispersing drug delivery systems is one of many approaches to increase the dissolution rate/solubility of these drugs.The overall aim of this doctoral dissertation is formulation, making and characterization of solid self-dispersing drug delivery systems with carbamazepine, using natural and synthetic solid carriers, in order to increase the dissolution rate and permeability of carbamazepine.In phase I of this research, proper selection of solid self-dispersing drug delivery systems, with different dispersity degree, for different oil/surfactant/cosurfactant (cosolvent) ratio was done. In the first part, after titration with water, pseudo-ternary phase diagrams were constructed for systems medium chain triglycerides/Polysorbate 80/Macrogol 400/water, and medium chain triglycerides/Cremophor® EL/Macrogol 400/water. Liquid self-emulsifying system (SEDDS) composed of medium chain triglycerides/Cremophor® EL/Macrogol 400, in a 10:66,75:22,25 ratio was selected. Furthermore, liquid self-nanoemulsifying system (SNEDDS) composed of medium chain triglycerides/Polysorbate 80/Transcutol® HP, in 20:60:20 ratio was also selected. Using mixture experimental design, liquid self-nanoemulsifying system (SNEDDS) composed of medium chain triglycerides/Polysorbate 80/Labrasol®/ Transcutol® HP, in 21,21:21,12:21,12:36,64 was selected. In this phase, a high matching between the predicted and the experimentally obtained values for droplet size and PdI was demonstrated.In phase II of the research, formulation, preparation and characterization of solid dispersing drug delivery systems were conducted. In its first stage, binary solid dispersions of carbamazepine and solid carriers (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320, diatomites) were prepared, varying the carbamazepine/carrier ratio (1:1, 1:2 and 1:6) and two formulation methods - evaporation of ethanol at room temperature, and at 70 °C. It was observed that solid dispersions made of Neusilin® UFL2, Neusilin® FL2 and Sylysia® 320, with carbamazepine/carrier ratios 1:2 and 1:6 leads to a significant increase in the dissolution rate of carbamazepine, whereas in formulations with a 1:1 carbamazepine/carrier ratio, and also in all formulations with diatomites, the dissolution rate of carbamazepine was similar to carbamazepine powder. In all formulations, carbamazepine was converted to the amorphous form or to polymorph form II. In the next stage of this phase, formulation, preparation and characterization of solid self-microemulsifying drug delivery systems with carbamazepine (SSMEDS) were done. The carbamazepine ratio was constant (20%), while the SMEDDS/carrier (Neusilin® UFL2, Neusilin® FL2, Sylysia® 320, diatomites) ratio was varied (1:1 and 3:1). Formulations were made using two methods (direct adsorption and evaporation with ethanol (99,5% v/v)). It was noted that the ethanol formulation method is not adequate, because of the conversion of carbamazepine into polymorph form II. A significant increase in the dissolution rate of carbamazepine from SSMEDS occurred (more than 90% in 30 minutes). The results of the dissolution test show that the dissolution rate of carbamazepine from SSMEDS formulations decreases with use of Neusilin® UFL2, Sylysia® 320, Neusilin® FL2 and diatomites, respectively. A significant difference in dissolution rate of carbamazepine from formulations with different carbamazepine/carrier ratio was not observed. Solid self-nanoemulsifying drug delivery system with carbamazepine (SSNEDS) was made by direct adsorption method, whereby carbamazepine ratio was constant (20%), and the SNEDDS/carrier (Neusilin® UFL2,Neusilin® FL2, Sylysia® 320, diatomites) ratio was varied (1:1 and 2:1)...",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Formulacija i karakterizacija čvrstih samo-dispergujućih nosača karbamazepina izrađenih sa poroznim adsorbensima, Formulation and characterization of solid self-dispersing carriers of carbamazepine prepared with porous adsorbents",
url = "https://hdl.handle.net/21.15107/rcub_nardus_4239"
}

Krstić, M.. (2015). Formulacija i karakterizacija čvrstih samo-dispergujućih nosača karbamazepina izrađenih sa poroznim adsorbensima. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_4239

Krstić M. Formulacija i karakterizacija čvrstih samo-dispergujućih nosača karbamazepina izrađenih sa poroznim adsorbensima. in Универзитет у Београду. 2015;.
https://hdl.handle.net/21.15107/rcub_nardus_4239 .

Krstić, Marko, "Formulacija i karakterizacija čvrstih samo-dispergujućih nosača karbamazepina izrađenih sa poroznim adsorbensima" in Универзитет у Београду (2015),
https://hdl.handle.net/21.15107/rcub_nardus_4239 .

TY  - JOUR
AU  - Bušatlić, Alma
AU  - Đogo-Mračević, Svetlana
AU  - Krstić, Marko
AU  - Bašić, Zorica
AU  - Ražić, Slavica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2509
AB  - Determination of sugars, especially in fruit juices, is very significant bearing in mind their nutritive importance and the increased demands in food control, especially for fractions of carbohydrates in fresh products. Home-made juices as 'functional food' are in the focus of scientific attention because of the expansion of industrial manufacturing of fruit juices and importance of monoand disaccharides stability for the products quality. In this work determination of content of basic sugars in fruit juices, by applying a high performance liquid chromatography (HPLC), was performed. Content of glucose, fructose and saccharose was analysed in currant, cherry, peach, apricot and strawberry juices as well as in home-made cherry and apricot syrups. Quantification was based on comparison of chromatograms of standard solutions of saccharose, glucose and fructose with our samples. With isocratic elution applied temperature was 90˚C, water as a mobile phase and column Nucleogel Sugar Ca, refractometric detection was applied. The obtained results showed that concentrations of gucose, fructose and saccharose vary in the range 3,149-38,405 g/100 mL, 1,931-30,851 g/100 mL and 0,670-6,072 g/100 mL, respectively. Concerntrations of glucose and fructose do not exhibit significant variations in juices however, they are ten times higher in syrups. In all samples, juices and syrups, concentrations of saccharose do not differ significantly, except for one syrup sample where much lower content could be explained with possible enzymatic decomposition.
AB  - Određivanje šećera u voćnim sokovima je veoma važno, imajući u vidu njihov nutritivni značaj, ali i povećane zahteve u kontroli hrane kada su u pitanju pojedine frakcije ugljenih hidrata u sveže pripremljenim proizvodima. S obzirom na to da postoji porast industrijske proizvodnje voćnih sokova i značaj stabilnosti monoi disaharida za kvalitet proizvoda, domaći sokovi, kao funkcionalna hrana, postaju sve značajniji. U ovom radu je analiziran sadržaj osnovnih šećera u voćnim sokovima i sirupima kućne izrade primenom visokoefikasne tečne hromatografije (HPLC). Analiziran je sadržaj glukoze, fruktoze i saharoze u sokovima od ribizle, višnje, breskve, kajsije i jagode, kao i u sirupima od višnje i kajsije. Određivanje se zasnivalo na poređenju hromatograma rastvora standarda šećera i naših uzoraka. Uz izokratsko eluiranje analiza je izvođena pri temperaturi od 90 ˚C. Sa vodom kao mobilnom fazom i kolonom Nucleogel Sugar Ca, primenjena je refraktometrijska detekcija. Analizom je pokazano da sadržaj glukoze, fruktoze i saharoze varira u rasponu 3,149-38,405 g/100 ml, 1,931-30,851 g/100 ml i 0,670-6,072 g/100 ml, respektivno. Sadržaj glukoze i fruktoze se ne razlikuje značajno između sokova, a u sirupima je za deset puta veći. Sadržaj saharoze takođe se ne razlikuje značajno među ispitivanim uzorcima, osim u jednom sirupu zbog najverovatnije enzimske razgradnje ovog šećera.
PB  - Društvo za ishranu Srbije, Beograd
T2  - Hrana i ishrana
T1  - Analysis of sugars in fruit juices using high performance liquid chromatography
T1  - Analiza šećera u voćnim sokovima primenom visokoefikasne tečne hromatografije
VL  - 56
IS  - 1
SP  - 16
EP  - 19
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2509
ER  - 

@article{
author = "Bušatlić, Alma and Đogo-Mračević, Svetlana and Krstić, Marko and Bašić, Zorica and Ražić, Slavica",
year = "2015",
abstract = "Determination of sugars, especially in fruit juices, is very significant bearing in mind their nutritive importance and the increased demands in food control, especially for fractions of carbohydrates in fresh products. Home-made juices as 'functional food' are in the focus of scientific attention because of the expansion of industrial manufacturing of fruit juices and importance of monoand disaccharides stability for the products quality. In this work determination of content of basic sugars in fruit juices, by applying a high performance liquid chromatography (HPLC), was performed. Content of glucose, fructose and saccharose was analysed in currant, cherry, peach, apricot and strawberry juices as well as in home-made cherry and apricot syrups. Quantification was based on comparison of chromatograms of standard solutions of saccharose, glucose and fructose with our samples. With isocratic elution applied temperature was 90˚C, water as a mobile phase and column Nucleogel Sugar Ca, refractometric detection was applied. The obtained results showed that concentrations of gucose, fructose and saccharose vary in the range 3,149-38,405 g/100 mL, 1,931-30,851 g/100 mL and 0,670-6,072 g/100 mL, respectively. Concerntrations of glucose and fructose do not exhibit significant variations in juices however, they are ten times higher in syrups. In all samples, juices and syrups, concentrations of saccharose do not differ significantly, except for one syrup sample where much lower content could be explained with possible enzymatic decomposition., Određivanje šećera u voćnim sokovima je veoma važno, imajući u vidu njihov nutritivni značaj, ali i povećane zahteve u kontroli hrane kada su u pitanju pojedine frakcije ugljenih hidrata u sveže pripremljenim proizvodima. S obzirom na to da postoji porast industrijske proizvodnje voćnih sokova i značaj stabilnosti monoi disaharida za kvalitet proizvoda, domaći sokovi, kao funkcionalna hrana, postaju sve značajniji. U ovom radu je analiziran sadržaj osnovnih šećera u voćnim sokovima i sirupima kućne izrade primenom visokoefikasne tečne hromatografije (HPLC). Analiziran je sadržaj glukoze, fruktoze i saharoze u sokovima od ribizle, višnje, breskve, kajsije i jagode, kao i u sirupima od višnje i kajsije. Određivanje se zasnivalo na poređenju hromatograma rastvora standarda šećera i naših uzoraka. Uz izokratsko eluiranje analiza je izvođena pri temperaturi od 90 ˚C. Sa vodom kao mobilnom fazom i kolonom Nucleogel Sugar Ca, primenjena je refraktometrijska detekcija. Analizom je pokazano da sadržaj glukoze, fruktoze i saharoze varira u rasponu 3,149-38,405 g/100 ml, 1,931-30,851 g/100 ml i 0,670-6,072 g/100 ml, respektivno. Sadržaj glukoze i fruktoze se ne razlikuje značajno između sokova, a u sirupima je za deset puta veći. Sadržaj saharoze takođe se ne razlikuje značajno među ispitivanim uzorcima, osim u jednom sirupu zbog najverovatnije enzimske razgradnje ovog šećera.",
publisher = "Društvo za ishranu Srbije, Beograd",
journal = "Hrana i ishrana",
title = "Analysis of sugars in fruit juices using high performance liquid chromatography, Analiza šećera u voćnim sokovima primenom visokoefikasne tečne hromatografije",
volume = "56",
number = "1",
pages = "16-19",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2509"
}

Bušatlić, A., Đogo-Mračević, S., Krstić, M., Bašić, Z.,& Ražić, S.. (2015). Analysis of sugars in fruit juices using high performance liquid chromatography. in Hrana i ishrana
Društvo za ishranu Srbije, Beograd., 56(1), 16-19.
https://hdl.handle.net/21.15107/rcub_farfar_2509

Bušatlić A, Đogo-Mračević S, Krstić M, Bašić Z, Ražić S. Analysis of sugars in fruit juices using high performance liquid chromatography. in Hrana i ishrana. 2015;56(1):16-19.
https://hdl.handle.net/21.15107/rcub_farfar_2509 .

Bušatlić, Alma, Đogo-Mračević, Svetlana, Krstić, Marko, Bašić, Zorica, Ražić, Slavica, "Analysis of sugars in fruit juices using high performance liquid chromatography" in Hrana i ishrana, 56, no. 1 (2015):16-19,
https://hdl.handle.net/21.15107/rcub_farfar_2509 .

TY  - JOUR
AU  - Krstić, Marko
AU  - Ražić, Slavica
AU  - Đekić, Ljiljana
AU  - Dobričić, Vladimir
AU  - Momcilović, Milica A.
AU  - Vasiljević, Dragana
AU  - Ibrić, Svetlana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2433
AB  - The purpose of this study was to investigate the solid self-emulsifying drug delivery system (SSEDDS), as a potential delivery system for poorly water soluble carbamazepine by application of mixture design. The self-emulsifying drug delivery system (SEDDS) was formulated using Polysorbate 80, Transcutol (R) HP and Mygliol (R) 812. The input parameters for mixture design (components of SSEDDS) were: appropriate SEDDS, carbamazepine and adsorbent, Neusilin (R) UFL2, with appropriate ranges 10-30%, 30-50% and 40-60%, respectively. The output parameters were the percentages of carbamazepine released after 10 and 30 min. The aim was to formulate SSEDDS with very fast drug release, i.e. more than 80% of carbamazepine has to be released in 30 min. Optimal formulations were examined through the dissolution test, parallel artificial membrane permeability assay (PAMPA), differential scanning calorimetry and thermal gravimetric analysis. With the obtained mixture design models, for any combination of factors ratios, it is possible to predict the profile of carbamazepine release. Optimal formulations exhibited significantly improved drug release and permeability.
PB  - Colegio Farmaceuticos Provincia De Buenos Aires, La Plata
T2  - Latin American Journal of Pharmacy
T1  - Application of a Mixture Experimental Design in the Optimization of the Formulation of Solid Self-Emulsifying Drug Delivery Systems Containing Carbamazepine
VL  - 34
IS  - 5
SP  - 885
EP  - 894
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2433
ER  - 

@article{
author = "Krstić, Marko and Ražić, Slavica and Đekić, Ljiljana and Dobričić, Vladimir and Momcilović, Milica A. and Vasiljević, Dragana and Ibrić, Svetlana",
year = "2015",
abstract = "The purpose of this study was to investigate the solid self-emulsifying drug delivery system (SSEDDS), as a potential delivery system for poorly water soluble carbamazepine by application of mixture design. The self-emulsifying drug delivery system (SEDDS) was formulated using Polysorbate 80, Transcutol (R) HP and Mygliol (R) 812. The input parameters for mixture design (components of SSEDDS) were: appropriate SEDDS, carbamazepine and adsorbent, Neusilin (R) UFL2, with appropriate ranges 10-30%, 30-50% and 40-60%, respectively. The output parameters were the percentages of carbamazepine released after 10 and 30 min. The aim was to formulate SSEDDS with very fast drug release, i.e. more than 80% of carbamazepine has to be released in 30 min. Optimal formulations were examined through the dissolution test, parallel artificial membrane permeability assay (PAMPA), differential scanning calorimetry and thermal gravimetric analysis. With the obtained mixture design models, for any combination of factors ratios, it is possible to predict the profile of carbamazepine release. Optimal formulations exhibited significantly improved drug release and permeability.",
publisher = "Colegio Farmaceuticos Provincia De Buenos Aires, La Plata",
journal = "Latin American Journal of Pharmacy",
title = "Application of a Mixture Experimental Design in the Optimization of the Formulation of Solid Self-Emulsifying Drug Delivery Systems Containing Carbamazepine",
volume = "34",
number = "5",
pages = "885-894",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2433"
}

Krstić, M., Ražić, S., Đekić, L., Dobričić, V., Momcilović, M. A., Vasiljević, D.,& Ibrić, S.. (2015). Application of a Mixture Experimental Design in the Optimization of the Formulation of Solid Self-Emulsifying Drug Delivery Systems Containing Carbamazepine. in Latin American Journal of Pharmacy
Colegio Farmaceuticos Provincia De Buenos Aires, La Plata., 34(5), 885-894.
https://hdl.handle.net/21.15107/rcub_farfar_2433

Krstić M, Ražić S, Đekić L, Dobričić V, Momcilović MA, Vasiljević D, Ibrić S. Application of a Mixture Experimental Design in the Optimization of the Formulation of Solid Self-Emulsifying Drug Delivery Systems Containing Carbamazepine. in Latin American Journal of Pharmacy. 2015;34(5):885-894.
https://hdl.handle.net/21.15107/rcub_farfar_2433 .

Krstić, Marko, Ražić, Slavica, Đekić, Ljiljana, Dobričić, Vladimir, Momcilović, Milica A., Vasiljević, Dragana, Ibrić, Svetlana, "Application of a Mixture Experimental Design in the Optimization of the Formulation of Solid Self-Emulsifying Drug Delivery Systems Containing Carbamazepine" in Latin American Journal of Pharmacy, 34, no. 5 (2015):885-894,
https://hdl.handle.net/21.15107/rcub_farfar_2433 .

TY  - JOUR
AU  - Krstić, Marko
AU  - Ražić, Slavica
AU  - Vasiljević, Dragana
AU  - Spasojević, Durdija
AU  - Ibrić, Svetlana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2406
AB  - Poor solubility is one of the key reasons for the poor bioavailability of carbamazepine drugs. This study considers formulation of solid surfactant systems with carbamazepine, in order to increase its dissolution rate. Solid-state surfactant systems were formed by application of fractional experimental design. Poloxamer 237 and Poloxamer 338 were used as the surfactants and Brij (R) 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied and their effects on the dissolution rate of carbamazepine were examined. Moreover, the effects of the addition of natural (diatomite) and a synthetic adsorbent carrier (Neusilin (R) UFL2) on the dissolution rate of carbamazepine were also tested. The prepared surfactant systems were characterized and the influences of the excipients on possible changes of the polymorphous form of carbamazepine examined by application of analytical techniques (DSC, TGA, FT-IR and PXRD). It was determined that an appropriate selection of the excipient type and ratio could provide a significant increase in the carbamazepine dissolution rate. By application of analytical techniques, it was found that the employed excipients induce a transition of carbamazepine into the amorphous form and that the selected sample was stable for three months, when kept under ambient conditions.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Application of experimental design in the examination of the dissolution rate of carbamazepine from formulations. Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis
VL  - 80
IS  - 2
SP  - 209
EP  - 222
DO  - 10.2298/JSC030814114K
ER  - 

@article{
author = "Krstić, Marko and Ražić, Slavica and Vasiljević, Dragana and Spasojević, Durdija and Ibrić, Svetlana",
year = "2015",
abstract = "Poor solubility is one of the key reasons for the poor bioavailability of carbamazepine drugs. This study considers formulation of solid surfactant systems with carbamazepine, in order to increase its dissolution rate. Solid-state surfactant systems were formed by application of fractional experimental design. Poloxamer 237 and Poloxamer 338 were used as the surfactants and Brij (R) 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied and their effects on the dissolution rate of carbamazepine were examined. Moreover, the effects of the addition of natural (diatomite) and a synthetic adsorbent carrier (Neusilin (R) UFL2) on the dissolution rate of carbamazepine were also tested. The prepared surfactant systems were characterized and the influences of the excipients on possible changes of the polymorphous form of carbamazepine examined by application of analytical techniques (DSC, TGA, FT-IR and PXRD). It was determined that an appropriate selection of the excipient type and ratio could provide a significant increase in the carbamazepine dissolution rate. By application of analytical techniques, it was found that the employed excipients induce a transition of carbamazepine into the amorphous form and that the selected sample was stable for three months, when kept under ambient conditions.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Application of experimental design in the examination of the dissolution rate of carbamazepine from formulations. Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis",
volume = "80",
number = "2",
pages = "209-222",
doi = "10.2298/JSC030814114K"
}

Krstić, M., Ražić, S., Vasiljević, D., Spasojević, D.,& Ibrić, S.. (2015). Application of experimental design in the examination of the dissolution rate of carbamazepine from formulations. Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 80(2), 209-222.
https://doi.org/10.2298/JSC030814114K

Krstić M, Ražić S, Vasiljević D, Spasojević D, Ibrić S. Application of experimental design in the examination of the dissolution rate of carbamazepine from formulations. Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis. in Journal of the Serbian Chemical Society. 2015;80(2):209-222.
doi:10.2298/JSC030814114K .

Krstić, Marko, Ražić, Slavica, Vasiljević, Dragana, Spasojević, Durdija, Ibrić, Svetlana, "Application of experimental design in the examination of the dissolution rate of carbamazepine from formulations. Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis" in Journal of the Serbian Chemical Society, 80, no. 2 (2015):209-222,
https://doi.org/10.2298/JSC030814114K . .

TY  - JOUR
AU  - Krstić, Marko
AU  - Popović, Miljana
AU  - Dobričić, Vladimir
AU  - Ibrić, Svetlana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2405
AB  - The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self-microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin((R)) UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin((R)) UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6) were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine.
PB  - MDPI, Basel
T2  - Molecules
T1  - Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability
VL  - 20
IS  - 8
SP  - 14684
EP  - 14698
DO  - 10.3390/molecules200814684
ER  - 

@article{
author = "Krstić, Marko and Popović, Miljana and Dobričić, Vladimir and Ibrić, Svetlana",
year = "2015",
abstract = "The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self-microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin((R)) UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin((R)) UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6) were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability",
volume = "20",
number = "8",
pages = "14684-14698",
doi = "10.3390/molecules200814684"
}

Krstić, M., Popović, M., Dobričić, V.,& Ibrić, S.. (2015). Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability. in Molecules
MDPI, Basel., 20(8), 14684-14698.
https://doi.org/10.3390/molecules200814684

Krstić M, Popović M, Dobričić V, Ibrić S. Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability. in Molecules. 2015;20(8):14684-14698.
doi:10.3390/molecules200814684 .

Krstić, Marko, Popović, Miljana, Dobričić, Vladimir, Ibrić, Svetlana, "Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability" in Molecules, 20, no. 8 (2015):14684-14698,
https://doi.org/10.3390/molecules200814684 . .

TY  - JOUR
AU  - Đuriš, Jelena
AU  - Medarević, Đorđe
AU  - Krstić, Marko
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1996
AB  - This study illustrates the application of experimental design and multivariate data analysis in defining design space for granulation and tableting processes. According to the quality by design concepts, critical quality attributes (CQAs) of granules and tablets, as well as critical parameters of granulation and tableting processes, were identified and evaluated. Acetaminophen was used as the model drug, and one of the study aims was to investigate the possibility of the development of immediate- or extended-release acetaminophen tablets. Granulation experiments were performed in the fluid bed processor using polyethylene oxide polymer as a binder in the direct granulation method. Tablets were compressed in the laboratory excenter tablet press. The first set of experiments was organized according to PlackettBurman design, followed by the full factorial experimental design. Principal component analysis and partial least squares regression were applied as the multivariate analysis techniques. By using these different methods, CQAs and process parameters were identified and quantified. Furthermore, an in-line method was developed to monitor the temperature during the fluidized bed granulation process, to foresee possible defects in granules CQAs. Various control strategies that are based on the process understanding and assure desired quality attributes of the product are proposed.
PB  - Elsevier Science Inc, New York
T2  - Journal of Pharmaceutical Sciences
T1  - Application of quality by design concepts in the development of fluidized bed granulation and tableting processes
VL  - 102
IS  - 6
SP  - 1869
EP  - 1882
DO  - 10.1002/jps.23530
ER  - 

@article{
author = "Đuriš, Jelena and Medarević, Đorđe and Krstić, Marko and Đurić, Zorica and Ibrić, Svetlana",
year = "2013",
abstract = "This study illustrates the application of experimental design and multivariate data analysis in defining design space for granulation and tableting processes. According to the quality by design concepts, critical quality attributes (CQAs) of granules and tablets, as well as critical parameters of granulation and tableting processes, were identified and evaluated. Acetaminophen was used as the model drug, and one of the study aims was to investigate the possibility of the development of immediate- or extended-release acetaminophen tablets. Granulation experiments were performed in the fluid bed processor using polyethylene oxide polymer as a binder in the direct granulation method. Tablets were compressed in the laboratory excenter tablet press. The first set of experiments was organized according to PlackettBurman design, followed by the full factorial experimental design. Principal component analysis and partial least squares regression were applied as the multivariate analysis techniques. By using these different methods, CQAs and process parameters were identified and quantified. Furthermore, an in-line method was developed to monitor the temperature during the fluidized bed granulation process, to foresee possible defects in granules CQAs. Various control strategies that are based on the process understanding and assure desired quality attributes of the product are proposed.",
publisher = "Elsevier Science Inc, New York",
journal = "Journal of Pharmaceutical Sciences",
title = "Application of quality by design concepts in the development of fluidized bed granulation and tableting processes",
volume = "102",
number = "6",
pages = "1869-1882",
doi = "10.1002/jps.23530"
}

Đuriš, J., Medarević, Đ., Krstić, M., Đurić, Z.,& Ibrić, S.. (2013). Application of quality by design concepts in the development of fluidized bed granulation and tableting processes. in Journal of Pharmaceutical Sciences
Elsevier Science Inc, New York., 102(6), 1869-1882.
https://doi.org/10.1002/jps.23530

Đuriš J, Medarević Đ, Krstić M, Đurić Z, Ibrić S. Application of quality by design concepts in the development of fluidized bed granulation and tableting processes. in Journal of Pharmaceutical Sciences. 2013;102(6):1869-1882.
doi:10.1002/jps.23530 .

Đuriš, Jelena, Medarević, Đorđe, Krstić, Marko, Đurić, Zorica, Ibrić, Svetlana, "Application of quality by design concepts in the development of fluidized bed granulation and tableting processes" in Journal of Pharmaceutical Sciences, 102, no. 6 (2013):1869-1882,
https://doi.org/10.1002/jps.23530 . .

TY  - JOUR
AU  - Đuriš, Jelena
AU  - Medarević, Đorđe
AU  - Krstić, Marko
AU  - Vasiljević, Ivana
AU  - Mašić, Ivana
AU  - Ibrić, Svetlana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1745
AB  - The aim of this study was to optimize fluid bed granulation and tablets compression processes using design space approach. Type of diluent, binder concentration, temperature during mixing, granulation and drying, spray rate, and atomization pressure were recognized as critical formulation and process parameters. They were varied in the first set of experiments in order to estimate their influences on critical quality attributes, that is, granules characteristics (size distribution, flowability, bulk density, tapped density, Carr's index, Hausner's ratio, and moisture content) using Plackett-Burman experimental design. Type of diluent and atomization pressure were selected as the most important parameters. In the second set of experiments, design space for process parameters (atomization pressure and compression force) and its influence on tablets characteristics was developed. Percent of paracetamol released and tablets hardness were determined as critical quality attributes. Artificial neural networks (ANNs) were applied in order to determine design space. ANNs models showed that atomization pressure influences mostly on the dissolution profile, whereas compression force affects mainly the tablets hardness. Based on the obtained ANNs models, it is possible to predict tablet hardness and paracetamol release profile for any combination of analyzed factors.
PB  - Hindawi Publishing Corporation, New York
T2  - Sensors
T1  - Design Space Approach in Optimization of Fluid Bed Granulation and Tablets Compression Process
DO  - 10.1100/2012/185085
ER  - 

@article{
author = "Đuriš, Jelena and Medarević, Đorđe and Krstić, Marko and Vasiljević, Ivana and Mašić, Ivana and Ibrić, Svetlana",
year = "2012",
abstract = "The aim of this study was to optimize fluid bed granulation and tablets compression processes using design space approach. Type of diluent, binder concentration, temperature during mixing, granulation and drying, spray rate, and atomization pressure were recognized as critical formulation and process parameters. They were varied in the first set of experiments in order to estimate their influences on critical quality attributes, that is, granules characteristics (size distribution, flowability, bulk density, tapped density, Carr's index, Hausner's ratio, and moisture content) using Plackett-Burman experimental design. Type of diluent and atomization pressure were selected as the most important parameters. In the second set of experiments, design space for process parameters (atomization pressure and compression force) and its influence on tablets characteristics was developed. Percent of paracetamol released and tablets hardness were determined as critical quality attributes. Artificial neural networks (ANNs) were applied in order to determine design space. ANNs models showed that atomization pressure influences mostly on the dissolution profile, whereas compression force affects mainly the tablets hardness. Based on the obtained ANNs models, it is possible to predict tablet hardness and paracetamol release profile for any combination of analyzed factors.",
publisher = "Hindawi Publishing Corporation, New York",
journal = "Sensors",
title = "Design Space Approach in Optimization of Fluid Bed Granulation and Tablets Compression Process",
doi = "10.1100/2012/185085"
}

Đuriš, J., Medarević, Đ., Krstić, M., Vasiljević, I., Mašić, I.,& Ibrić, S.. (2012). Design Space Approach in Optimization of Fluid Bed Granulation and Tablets Compression Process. in Sensors
Hindawi Publishing Corporation, New York..
https://doi.org/10.1100/2012/185085

Đuriš J, Medarević Đ, Krstić M, Vasiljević I, Mašić I, Ibrić S. Design Space Approach in Optimization of Fluid Bed Granulation and Tablets Compression Process. in Sensors. 2012;.
doi:10.1100/2012/185085 .

Đuriš, Jelena, Medarević, Đorđe, Krstić, Marko, Vasiljević, Ivana, Mašić, Ivana, Ibrić, Svetlana, "Design Space Approach in Optimization of Fluid Bed Granulation and Tablets Compression Process" in Sensors (2012),
https://doi.org/10.1100/2012/185085 . .