TY  - JOUR
AU  - Kovačević, Jovana
AU  - Kovačević, Aleksandar
AU  - Miletić, Tijana
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4413
AB  - Understanding the effect of the characteristics of formulation and process parameters on
the physicochemical properties of a pharmaceutical product is very significant for the
development of solid dosage forms, as the knowledge gained on small scale batches in the early
phase of development is used in the later phases of product lifecycle or in the development of
other products. One of the approaches for gaining a better understanding of the effects of the
formulation and production process on the quality of the finished product is to apply a
systematical approach which concerns performing experiments according to a predefined factorial
or fractional factorial experimental plan. However, often it is the case that there are available data
gathered in a non-systematic way, because experiments were not performed according to a
predetermined experimental plan. In such a case, data mining techniques could be used to extract
useful data from the historical data set. In this research, the possibility of using several data mining
techniques to build models that describe the effect of formulation characteristics on acid resistance
and dissolution profile of a model drug from gastro-resistant pellets. The model drug used in the
research is duloxetine hydrochloride from the group of antidepressants. It belongs to the BCS 2
class of active pharmaceutical ingredients, and it is therefore necessary for the release profile of
duloxetine to be characterized by a higher number of tested time points. The developed models
can be used for planning future laboratory trials, or in the development of other products.
AB  - Razumevanje uticaja karakteristika formulacije i procesnih parametara na fizičkohemijske osobine farmaceutskog proizvoda je vrlo značajno u razvoju čvrstih doziranih oblika jer se znanje stečeno u fazi razvoja koristi i u svim sledećim fazama životnog ciklusa proizvoda, a može da se primeni i u razvoju drugih proizvoda. Jedan pristup ka postizanju boljeg poznavanja proizvoda i procesa je primena sistematičnog pristupa koji podrazumeva izvođenje eksperimenata u skladu sa predefinisanim faktorijalnim ili frakcionim faktorijalnim eksperiementalnim planom. Međutim, čest je slučaj da dostupni podaci nisu prikupljeni na sistematičan način zato što eksperimenti nisu izvođeni po predefinisanom planu. Tada se mogu primeniti tehnike istraživanja i analize podataka da bi se iz seta istorijskih podataka izdvojili korisni podaci. U ovom istraživanju smo ispitali mogućnost korišćenja različitih tehnika istraživanja i analize podataka za razvoj modela koji opisuju efekte formulacije na gastrorezistenciju i profil oslobađanja model supstance iz gastrorezistentnih peleta. Model supstanca je duloksetin hidrohlorid iz grupe antidepresiva. Pripada BCS 2 klasi lekovitih supstanci, te je poželjno da profil brzine rastvaranja duloksetina iz peleta bude okarakterisan većim brojem vremenskih tačaka. Razvijeni modeli se mogu koristiti za planiranje narednih proba ili u razvoju drugih proizvoda.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Data mining techniques applied in the analysis of historical data
T1  - Tehnika istraživanja i analize podataka primenjena u analizi istorijskih podataka
VL  - 72
IS  - 6
SP  - 701
EP  - 715
DO  - 10.5937/arhfarm72-41368
ER  - 

@article{
author = "Kovačević, Jovana and Kovačević, Aleksandar and Miletić, Tijana and Đuriš, Jelena and Ibrić, Svetlana",
year = "2022",
abstract = "Understanding the effect of the characteristics of formulation and process parameters on
the physicochemical properties of a pharmaceutical product is very significant for the
development of solid dosage forms, as the knowledge gained on small scale batches in the early
phase of development is used in the later phases of product lifecycle or in the development of
other products. One of the approaches for gaining a better understanding of the effects of the
formulation and production process on the quality of the finished product is to apply a
systematical approach which concerns performing experiments according to a predefined factorial
or fractional factorial experimental plan. However, often it is the case that there are available data
gathered in a non-systematic way, because experiments were not performed according to a
predetermined experimental plan. In such a case, data mining techniques could be used to extract
useful data from the historical data set. In this research, the possibility of using several data mining
techniques to build models that describe the effect of formulation characteristics on acid resistance
and dissolution profile of a model drug from gastro-resistant pellets. The model drug used in the
research is duloxetine hydrochloride from the group of antidepressants. It belongs to the BCS 2
class of active pharmaceutical ingredients, and it is therefore necessary for the release profile of
duloxetine to be characterized by a higher number of tested time points. The developed models
can be used for planning future laboratory trials, or in the development of other products., Razumevanje uticaja karakteristika formulacije i procesnih parametara na fizičkohemijske osobine farmaceutskog proizvoda je vrlo značajno u razvoju čvrstih doziranih oblika jer se znanje stečeno u fazi razvoja koristi i u svim sledećim fazama životnog ciklusa proizvoda, a može da se primeni i u razvoju drugih proizvoda. Jedan pristup ka postizanju boljeg poznavanja proizvoda i procesa je primena sistematičnog pristupa koji podrazumeva izvođenje eksperimenata u skladu sa predefinisanim faktorijalnim ili frakcionim faktorijalnim eksperiementalnim planom. Međutim, čest je slučaj da dostupni podaci nisu prikupljeni na sistematičan način zato što eksperimenti nisu izvođeni po predefinisanom planu. Tada se mogu primeniti tehnike istraživanja i analize podataka da bi se iz seta istorijskih podataka izdvojili korisni podaci. U ovom istraživanju smo ispitali mogućnost korišćenja različitih tehnika istraživanja i analize podataka za razvoj modela koji opisuju efekte formulacije na gastrorezistenciju i profil oslobađanja model supstance iz gastrorezistentnih peleta. Model supstanca je duloksetin hidrohlorid iz grupe antidepresiva. Pripada BCS 2 klasi lekovitih supstanci, te je poželjno da profil brzine rastvaranja duloksetina iz peleta bude okarakterisan većim brojem vremenskih tačaka. Razvijeni modeli se mogu koristiti za planiranje narednih proba ili u razvoju drugih proizvoda.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Data mining techniques applied in the analysis of historical data, Tehnika istraživanja i analize podataka primenjena u analizi istorijskih podataka",
volume = "72",
number = "6",
pages = "701-715",
doi = "10.5937/arhfarm72-41368"
}

Kovačević, J., Kovačević, A., Miletić, T., Đuriš, J.,& Ibrić, S.. (2022). Data mining techniques applied in the analysis of historical data. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(6), 701-715.
https://doi.org/10.5937/arhfarm72-41368

Kovačević J, Kovačević A, Miletić T, Đuriš J, Ibrić S. Data mining techniques applied in the analysis of historical data. in Arhiv za farmaciju. 2022;72(6):701-715.
doi:10.5937/arhfarm72-41368 .

Kovačević, Jovana, Kovačević, Aleksandar, Miletić, Tijana, Đuriš, Jelena, Ibrić, Svetlana, "Data mining techniques applied in the analysis of historical data" in Arhiv za farmaciju, 72, no. 6 (2022):701-715,
https://doi.org/10.5937/arhfarm72-41368 . .

TY  - JOUR
AU  - Nikolić, Nenad
AU  - Miletić, Tijana
AU  - Kovačević, Jovana
AU  - Medarević, Đorđe
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4407
AB  - Compaction simulators are designed as machines which can provide an in-depth analysis
of the powder compaction process. Characterization of the powder compression and compaction
process, as well as material characterization, play an important role in the formulation and
manufacturing process design and development, as well as in creating a strong knowledge basis
for the scale-up of the tablet compression and troubleshooting in further stages of the product
lifecycle. Although compaction simulators are designed to simulate the compression process on
high-speed tablet-presses, with the advantages of a small quantity of material needed and highly
sophisticated instrumentation, there are certain limitations in the extrapolation of the process
parameters from these machines to high-speed rotary tablet presses. However, the advantage of
the use of compaction simulators for studying basic compression and compaction mechanisms,
identification of critical material attributes and critical process parameters ranges, and their
relations with tablet characteristics and critical quality attributes of pharmaceutical products is
clear, compared to the use of small excentre tablet presses, and complementary to the use of small
rotary tablet presses.
This scientific paper provides an overview and examples of the different advantages
provided by the instrumentation of compaction simulators, including certain limitations in their
exploitation.
AB  - Simulatori kompaktiranja su uređaji dizajnirani da omoguće dublju analizu procesa komprimovanja praškova. Karakterizacija procesa kompresije i kompakcije praškova, kao i karakterizacija materijala, ima važnu ulogu u dizajnu i razvoju formulacije i proizvodnog procesa tableta, kao i za kreiranje snažne baze za transfer proizvodnog procesa komprimovanja tableta na proizvodnu opremu i rešavanje problema u proizvodnim procesima u kasnijim fazama životnog ciklusa proizvoda. Iako su simulatori kompaktiranja dizajnirani da simuliraju proces kompresije na tablet-presama visoke brzine, obezbeđujući prednost korišćenja manjih količina materijala i visoko sofisticirane instrumentacije, postoje određena ograničenja u ekstrapolaciji procesnih parametara sa ovih mašina na tablet-prese visokih brzina. Međutim, prednosti upotrebe simulatora kompaktiranja za proučavanje osnovnih mehanizama kompresije i kompaktiranja, identifikaciju kritičnih karakteristika materijala i opsega kritičnih procesnih parametara, kao i njihovih relacija sa karakteristikama tableta, i kritičnim karakteristikama farmaceutskih proizvoda su očigledne, u poređenju sa korišćenjem malih ekscenter tablet presa, i komplementarne sa upotrebom manjih rotacionih tablet presa. U ovom radu je prikazan pregled i primeri različitih prednosti omogućenih nivoom instrumentacije simulatora kompaktiranja, uključujući i ograničenja u njihovoj eksploataciji.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Usage of compaction simulators for the powder compression characterization – advantages and limitations
T1  - Upotreba simulatora kompaktiranja za karakterizaciju kompresije praškova - prednosti i ograničenja
VL  - 72
IS  - 6
SP  - 546
EP  - 565
DO  - 10.5937/arhfarm72-41301
ER  - 

@article{
author = "Nikolić, Nenad and Miletić, Tijana and Kovačević, Jovana and Medarević, Đorđe and Ibrić, Svetlana",
year = "2022",
abstract = "Compaction simulators are designed as machines which can provide an in-depth analysis
of the powder compaction process. Characterization of the powder compression and compaction
process, as well as material characterization, play an important role in the formulation and
manufacturing process design and development, as well as in creating a strong knowledge basis
for the scale-up of the tablet compression and troubleshooting in further stages of the product
lifecycle. Although compaction simulators are designed to simulate the compression process on
high-speed tablet-presses, with the advantages of a small quantity of material needed and highly
sophisticated instrumentation, there are certain limitations in the extrapolation of the process
parameters from these machines to high-speed rotary tablet presses. However, the advantage of
the use of compaction simulators for studying basic compression and compaction mechanisms,
identification of critical material attributes and critical process parameters ranges, and their
relations with tablet characteristics and critical quality attributes of pharmaceutical products is
clear, compared to the use of small excentre tablet presses, and complementary to the use of small
rotary tablet presses.
This scientific paper provides an overview and examples of the different advantages
provided by the instrumentation of compaction simulators, including certain limitations in their
exploitation., Simulatori kompaktiranja su uređaji dizajnirani da omoguće dublju analizu procesa komprimovanja praškova. Karakterizacija procesa kompresije i kompakcije praškova, kao i karakterizacija materijala, ima važnu ulogu u dizajnu i razvoju formulacije i proizvodnog procesa tableta, kao i za kreiranje snažne baze za transfer proizvodnog procesa komprimovanja tableta na proizvodnu opremu i rešavanje problema u proizvodnim procesima u kasnijim fazama životnog ciklusa proizvoda. Iako su simulatori kompaktiranja dizajnirani da simuliraju proces kompresije na tablet-presama visoke brzine, obezbeđujući prednost korišćenja manjih količina materijala i visoko sofisticirane instrumentacije, postoje određena ograničenja u ekstrapolaciji procesnih parametara sa ovih mašina na tablet-prese visokih brzina. Međutim, prednosti upotrebe simulatora kompaktiranja za proučavanje osnovnih mehanizama kompresije i kompaktiranja, identifikaciju kritičnih karakteristika materijala i opsega kritičnih procesnih parametara, kao i njihovih relacija sa karakteristikama tableta, i kritičnim karakteristikama farmaceutskih proizvoda su očigledne, u poređenju sa korišćenjem malih ekscenter tablet presa, i komplementarne sa upotrebom manjih rotacionih tablet presa. U ovom radu je prikazan pregled i primeri različitih prednosti omogućenih nivoom instrumentacije simulatora kompaktiranja, uključujući i ograničenja u njihovoj eksploataciji.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Usage of compaction simulators for the powder compression characterization – advantages and limitations, Upotreba simulatora kompaktiranja za karakterizaciju kompresije praškova - prednosti i ograničenja",
volume = "72",
number = "6",
pages = "546-565",
doi = "10.5937/arhfarm72-41301"
}

Nikolić, N., Miletić, T., Kovačević, J., Medarević, Đ.,& Ibrić, S.. (2022). Usage of compaction simulators for the powder compression characterization – advantages and limitations. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(6), 546-565.
https://doi.org/10.5937/arhfarm72-41301

Nikolić N, Miletić T, Kovačević J, Medarević Đ, Ibrić S. Usage of compaction simulators for the powder compression characterization – advantages and limitations. in Arhiv za farmaciju. 2022;72(6):546-565.
doi:10.5937/arhfarm72-41301 .

Nikolić, Nenad, Miletić, Tijana, Kovačević, Jovana, Medarević, Đorđe, Ibrić, Svetlana, "Usage of compaction simulators for the powder compression characterization – advantages and limitations" in Arhiv za farmaciju, 72, no. 6 (2022):546-565,
https://doi.org/10.5937/arhfarm72-41301 . .

TY  - JOUR
AU  - Miletić, Tijana
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2188
AB  - The aim of this study was to investigate the usefulness of combined application of quality by design tools such as central composite design (CCD), response surface methodology (RSM), and artificial neural networks (ANN) in the characterization, modeling, and optimizaton of spray drying of a poorly soluble drug : cyclodextrin complex. Models were developed by RSM and ANN from different pools of data. The model with best predictability was the ANN multilayer perceptron (MLP)1 model developed from the largest group of data (R-2 for response yield 0.854, moisture content 0.886). On the other hand, analysis of equations derived from the application of RSM contributed in better understanding the complex relationships between input and output variables. By application of a desirability function approach, optimal process parameters that resulted in the best process yield (86%) and minimal moisture content in the powder (3.3%) were established (25% feed concentration, 180 degrees C inlet air temperature, 10% pump speed).
PB  - Taylor & Francis Inc, Philadelphia
T2  - Drying Technology
T1  - Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes
VL  - 32
IS  - 2
SP  - 167
EP  - 179
DO  - 10.1080/07373937.2013.811593
ER  - 

@article{
author = "Miletić, Tijana and Ibrić, Svetlana and Đurić, Zorica",
year = "2014",
abstract = "The aim of this study was to investigate the usefulness of combined application of quality by design tools such as central composite design (CCD), response surface methodology (RSM), and artificial neural networks (ANN) in the characterization, modeling, and optimizaton of spray drying of a poorly soluble drug : cyclodextrin complex. Models were developed by RSM and ANN from different pools of data. The model with best predictability was the ANN multilayer perceptron (MLP)1 model developed from the largest group of data (R-2 for response yield 0.854, moisture content 0.886). On the other hand, analysis of equations derived from the application of RSM contributed in better understanding the complex relationships between input and output variables. By application of a desirability function approach, optimal process parameters that resulted in the best process yield (86%) and minimal moisture content in the powder (3.3%) were established (25% feed concentration, 180 degrees C inlet air temperature, 10% pump speed).",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Drying Technology",
title = "Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes",
volume = "32",
number = "2",
pages = "167-179",
doi = "10.1080/07373937.2013.811593"
}

Miletić, T., Ibrić, S.,& Đurić, Z.. (2014). Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes. in Drying Technology
Taylor & Francis Inc, Philadelphia., 32(2), 167-179.
https://doi.org/10.1080/07373937.2013.811593

Miletić T, Ibrić S, Đurić Z. Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes. in Drying Technology. 2014;32(2):167-179.
doi:10.1080/07373937.2013.811593 .

Miletić, Tijana, Ibrić, Svetlana, Đurić, Zorica, "Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes" in Drying Technology, 32, no. 2 (2014):167-179,
https://doi.org/10.1080/07373937.2013.811593 . .

TY  - JOUR
AU  - Miletić, Tijana
AU  - Kyriakos, Kachrimanis
AU  - Graovac, Adrijana
AU  - Ibrić, Svetlana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1841
AB  - The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug-cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulations showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation.
PB  - Elsevier Sci Ltd, Oxford
T2  - Carbohydrate Polymers
T1  - Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability
VL  - 98
IS  - 1
SP  - 122
EP  - 131
DO  - 10.1016/j.carbpol.2013.05.084
ER  - 

@article{
author = "Miletić, Tijana and Kyriakos, Kachrimanis and Graovac, Adrijana and Ibrić, Svetlana",
year = "2013",
abstract = "The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug-cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulations showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Carbohydrate Polymers",
title = "Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability",
volume = "98",
number = "1",
pages = "122-131",
doi = "10.1016/j.carbpol.2013.05.084"
}

Miletić, T., Kyriakos, K., Graovac, A.,& Ibrić, S.. (2013). Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability. in Carbohydrate Polymers
Elsevier Sci Ltd, Oxford., 98(1), 122-131.
https://doi.org/10.1016/j.carbpol.2013.05.084

Miletić T, Kyriakos K, Graovac A, Ibrić S. Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability. in Carbohydrate Polymers. 2013;98(1):122-131.
doi:10.1016/j.carbpol.2013.05.084 .

Miletić, Tijana, Kyriakos, Kachrimanis, Graovac, Adrijana, Ibrić, Svetlana, "Spray-dried voriconazole-cyclodextrin complexes: Solubility, dissolution rate and chemical stability" in Carbohydrate Polymers, 98, no. 1 (2013):122-131,
https://doi.org/10.1016/j.carbpol.2013.05.084 . .