TY  - JOUR
AU  - Solomun, Ljiljana
AU  - Ibrić, Svetlana
AU  - Pejanović, Vjera M.
AU  - Đuriš, Jelena
AU  - Jocković, Jelena
AU  - Stanković, Predrag
AU  - Vujić, Zorica
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1763
AB  - This article presents the possibility of using of multiple regression analysis (MRA) and dynamic neural network (DNN) for prediction of stability of Hydrocortisone 100 mg (in a form of hydrocortisone sodium succinate) freeze-dried powder for injection packed into a dual chamber container. Degradation products of hydrocortisone sodium succinate - free hydrocortisone and related substances (impurities A, B, C, D and E; unspecified impurities and total impurities) - were followed during stress and formal stability studies. All data obtained during stability studies were used for in silico modeling; multiple regression models and dynamic neural networks as well, in order to compare predicted and observed results. High values of coefficient of determination (0.95?0.99) were gained using MRA and DNN, so both methods are powerful tools for in silico stability studies, but superiority of DNN over mathematical modeling of degradation was also confirmed.
AB  - Radi bezbednije, brže i efikasnije parenteralne primene hidrokortizona, široko primenjivanog kortikosteroida, ispitivan je sistem kontaktnog pakovanja u kome se i liofilizat i rastvor za rekonstituciju nalaze u jednoj, dvokomornoj bočici. Ispitivanje je izvedeno na preparatu Hidrokortizon, 100 mg, liofilizat za rastvor za injekcije. Inicijalno postavljeni parametri kvaliteta su provereni prvo kroz studije stres stabilnosti sa posebnim akcentom na promenu koncentracije slobodnog hidrokortizona, odnosno definisanje degradacionog profila ispitivanog proizvoda. Ispitivanje je vršeno pod uslovima povišene temperature (40 , 50 i 60 °C) u trajanju od tri, odnosno šest meseci. Rezultati su pokazali da dolazi do porasta koncentracije slobodnog hidrokortizona u funkciji vremena i temperature. Takođe, detekovano je prisustvo pet degradacionih proizvoda. Dobijeni rezultati u toku stres ispitivanja stabilnosti su korišćeni u statističkim proračunima. Potvrda kako definisanog kvaliteta proizvoda, tako i predviđanja stabilnosti korišćenjem in silico metoda, dobijena je kroz ispitivanje stabilnosti metodom formalnog ispitivanja, pod uslovima ubrzanog (40 °C/75% RH), intermedijernog (30 °C/65% RH) i dugotrajnog starenja (25 °C/60% RH). Tokom ispitivanja, detektuje se porast koncentracije slobodnog hidrokortizona, ali i srodnih supstanci (nečistoća) koje se javljaju pod uticajem temperature (nečistoće A, B, D i E), odnosno C koja je proizvod fotodegradacije. Ovi degradacioni proizvodi nastaju intramolekulskim premeštanjima. U opisivanju brzine degradacije hidrokortizona, korišćene su metode multiple regresione analize (MRA) i dinamičke neuronske mreže (DNM), a dobijeni rezultati su poređeni sa rezultatima ispitivanja uzorka pod uslovima ubrzanog i dugotrajnog starenja. Primenom MRA dobijene su visoke vrednosti koeficijenta korelacije (R2 od 0,95 do 0,99), osim za slobodni hidrokortizon (0,65), nečistoću C (0,73) i slobodne nespecificirane (0,74), što pokazuje da postoji dobra korelacija između predviđenih i eksperimentalno dobijenih odgovora. Kada je primenjena neuronska mreža tipa RJDM, visoke vrednosti koeficijenta korelacije (od 0,96 do 0,99) pokazuju da je mreža obučena da predvidi stepen degradacije hidrokortizona na 25 oC u različitim vremenskim intervalima. Dobijeni rezultati pokazuju da se obe in silico metode mogu uspešno koristiti u predviđanju procenta nečistoća i brzine degradacije lekovitih supstanci. Prednost korišćenja neuronskih mreža je ta, što je sa njom moguće istovremeno manipulisati sa svim odgovorima (tj. nečistoćama), tj. vrlo jednostavno, jednom kada je mreža istrenirana, predvideti koncentracije svih nečistoća ispitivanih preparata na bilo kojoj temperaturi i u bilo kom vremenu.
PB  - Savez hemijskih inženjera, Beograd
T2  - Hemijska industrija
T1  - In silico methods in stability testing of Hydrocortisone, powder for injections: Multiple regression analysis versus dynamic neural network
T1  - In silico metode u ispitivanju stabilnosti hidrokortizona, liofilizata za infuziju - višestruka regresiona analiza i dinamičke neuronske mreže
VL  - 66
IS  - 5
SP  - 647
EP  - 657
DO  - 10.2298/HEMIND120207023S
ER  - 

@article{
author = "Solomun, Ljiljana and Ibrić, Svetlana and Pejanović, Vjera M. and Đuriš, Jelena and Jocković, Jelena and Stanković, Predrag and Vujić, Zorica",
year = "2012",
abstract = "This article presents the possibility of using of multiple regression analysis (MRA) and dynamic neural network (DNN) for prediction of stability of Hydrocortisone 100 mg (in a form of hydrocortisone sodium succinate) freeze-dried powder for injection packed into a dual chamber container. Degradation products of hydrocortisone sodium succinate - free hydrocortisone and related substances (impurities A, B, C, D and E; unspecified impurities and total impurities) - were followed during stress and formal stability studies. All data obtained during stability studies were used for in silico modeling; multiple regression models and dynamic neural networks as well, in order to compare predicted and observed results. High values of coefficient of determination (0.95?0.99) were gained using MRA and DNN, so both methods are powerful tools for in silico stability studies, but superiority of DNN over mathematical modeling of degradation was also confirmed., Radi bezbednije, brže i efikasnije parenteralne primene hidrokortizona, široko primenjivanog kortikosteroida, ispitivan je sistem kontaktnog pakovanja u kome se i liofilizat i rastvor za rekonstituciju nalaze u jednoj, dvokomornoj bočici. Ispitivanje je izvedeno na preparatu Hidrokortizon, 100 mg, liofilizat za rastvor za injekcije. Inicijalno postavljeni parametri kvaliteta su provereni prvo kroz studije stres stabilnosti sa posebnim akcentom na promenu koncentracije slobodnog hidrokortizona, odnosno definisanje degradacionog profila ispitivanog proizvoda. Ispitivanje je vršeno pod uslovima povišene temperature (40 , 50 i 60 °C) u trajanju od tri, odnosno šest meseci. Rezultati su pokazali da dolazi do porasta koncentracije slobodnog hidrokortizona u funkciji vremena i temperature. Takođe, detekovano je prisustvo pet degradacionih proizvoda. Dobijeni rezultati u toku stres ispitivanja stabilnosti su korišćeni u statističkim proračunima. Potvrda kako definisanog kvaliteta proizvoda, tako i predviđanja stabilnosti korišćenjem in silico metoda, dobijena je kroz ispitivanje stabilnosti metodom formalnog ispitivanja, pod uslovima ubrzanog (40 °C/75% RH), intermedijernog (30 °C/65% RH) i dugotrajnog starenja (25 °C/60% RH). Tokom ispitivanja, detektuje se porast koncentracije slobodnog hidrokortizona, ali i srodnih supstanci (nečistoća) koje se javljaju pod uticajem temperature (nečistoće A, B, D i E), odnosno C koja je proizvod fotodegradacije. Ovi degradacioni proizvodi nastaju intramolekulskim premeštanjima. U opisivanju brzine degradacije hidrokortizona, korišćene su metode multiple regresione analize (MRA) i dinamičke neuronske mreže (DNM), a dobijeni rezultati su poređeni sa rezultatima ispitivanja uzorka pod uslovima ubrzanog i dugotrajnog starenja. Primenom MRA dobijene su visoke vrednosti koeficijenta korelacije (R2 od 0,95 do 0,99), osim za slobodni hidrokortizon (0,65), nečistoću C (0,73) i slobodne nespecificirane (0,74), što pokazuje da postoji dobra korelacija između predviđenih i eksperimentalno dobijenih odgovora. Kada je primenjena neuronska mreža tipa RJDM, visoke vrednosti koeficijenta korelacije (od 0,96 do 0,99) pokazuju da je mreža obučena da predvidi stepen degradacije hidrokortizona na 25 oC u različitim vremenskim intervalima. Dobijeni rezultati pokazuju da se obe in silico metode mogu uspešno koristiti u predviđanju procenta nečistoća i brzine degradacije lekovitih supstanci. Prednost korišćenja neuronskih mreža je ta, što je sa njom moguće istovremeno manipulisati sa svim odgovorima (tj. nečistoćama), tj. vrlo jednostavno, jednom kada je mreža istrenirana, predvideti koncentracije svih nečistoća ispitivanih preparata na bilo kojoj temperaturi i u bilo kom vremenu.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "Hemijska industrija",
title = "In silico methods in stability testing of Hydrocortisone, powder for injections: Multiple regression analysis versus dynamic neural network, In silico metode u ispitivanju stabilnosti hidrokortizona, liofilizata za infuziju - višestruka regresiona analiza i dinamičke neuronske mreže",
volume = "66",
number = "5",
pages = "647-657",
doi = "10.2298/HEMIND120207023S"
}

Solomun, L., Ibrić, S., Pejanović, V. M., Đuriš, J., Jocković, J., Stanković, P.,& Vujić, Z.. (2012). In silico methods in stability testing of Hydrocortisone, powder for injections: Multiple regression analysis versus dynamic neural network. in Hemijska industrija
Savez hemijskih inženjera, Beograd., 66(5), 647-657.
https://doi.org/10.2298/HEMIND120207023S

Solomun L, Ibrić S, Pejanović VM, Đuriš J, Jocković J, Stanković P, Vujić Z. In silico methods in stability testing of Hydrocortisone, powder for injections: Multiple regression analysis versus dynamic neural network. in Hemijska industrija. 2012;66(5):647-657.
doi:10.2298/HEMIND120207023S .

Solomun, Ljiljana, Ibrić, Svetlana, Pejanović, Vjera M., Đuriš, Jelena, Jocković, Jelena, Stanković, Predrag, Vujić, Zorica, "In silico methods in stability testing of Hydrocortisone, powder for injections: Multiple regression analysis versus dynamic neural network" in Hemijska industrija, 66, no. 5 (2012):647-657,
https://doi.org/10.2298/HEMIND120207023S . .

TY  - JOUR
AU  - Đekić, Ljiljana
AU  - Primorac, Marija
AU  - Jocković, Jelena
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1572
AB  - This study investigated phase behaviour, microstructure and solubilization capacity of pseudo-ternary surfactant/cosurfactant/isopropyl myristate/water systems employing complex mixtures of nonionic surfactants for formation of single-phase microemulsions. The surfactant was PEG-8 caprylic/capric glycerides (Labrasol (R)). A well defined mixture of octoxynol-12 and polysorbate 20 and/or PEG-40 hydrogenated castor oil, available as commercial nonionicsurfactants Solubilisant gamma (R) 2421, Solubilisant gamma (R) 2429 and Cremophor (R) RH 40, respectively, were evaluated as cosurfactants. Surfactant + cosurfactant mixtures were treated as a single component (pseudo-component), since a surfactant-to-cosurfactant weight ratio (Km 50:50) was constant through the study. Phase behaviour study revealed enlargement of single-phase microemulsion area as surfactant + cosurfactant-to-oil weight ratio (SCoS/O) increases. The formation of fully dilutable microemulsions containing the maximum of water incorporation in the surfactant/cosurfactant/oil preconcentrates of W(max) >= 80% w/w, was achieved at SCoS/O 90:10. Microemulsions formed along the single-phase sequence at SCoS/O 90:10 in the presence of different cosurfactants, were characterized using polarized light microscopy, photon correlation spectroscopy (PCS), and rheological measurements. Different performances of complex mixtures of nonionic surfactants in stabilization of single-phase microemulsions were observed only in highly diluted oil-in-water microemulsions area. Investigation of solubilization capacity for poorly soluble drug ibuprofen revealed the critical importance of water-to-surfactant + cosurfactant ratio and penetration of oil at the interface.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Molecular Liquids
T1  - Phase behaviour, microstructure and ibuprofen solubilization capacity of pseudo-ternary nonionic microemulsions
VL  - 160
IS  - 2
SP  - 81
EP  - 87
DO  - 10.1016/j.molliq.2011.02.010
ER  - 

@article{
author = "Đekić, Ljiljana and Primorac, Marija and Jocković, Jelena",
year = "2011",
abstract = "This study investigated phase behaviour, microstructure and solubilization capacity of pseudo-ternary surfactant/cosurfactant/isopropyl myristate/water systems employing complex mixtures of nonionic surfactants for formation of single-phase microemulsions. The surfactant was PEG-8 caprylic/capric glycerides (Labrasol (R)). A well defined mixture of octoxynol-12 and polysorbate 20 and/or PEG-40 hydrogenated castor oil, available as commercial nonionicsurfactants Solubilisant gamma (R) 2421, Solubilisant gamma (R) 2429 and Cremophor (R) RH 40, respectively, were evaluated as cosurfactants. Surfactant + cosurfactant mixtures were treated as a single component (pseudo-component), since a surfactant-to-cosurfactant weight ratio (Km 50:50) was constant through the study. Phase behaviour study revealed enlargement of single-phase microemulsion area as surfactant + cosurfactant-to-oil weight ratio (SCoS/O) increases. The formation of fully dilutable microemulsions containing the maximum of water incorporation in the surfactant/cosurfactant/oil preconcentrates of W(max) >= 80% w/w, was achieved at SCoS/O 90:10. Microemulsions formed along the single-phase sequence at SCoS/O 90:10 in the presence of different cosurfactants, were characterized using polarized light microscopy, photon correlation spectroscopy (PCS), and rheological measurements. Different performances of complex mixtures of nonionic surfactants in stabilization of single-phase microemulsions were observed only in highly diluted oil-in-water microemulsions area. Investigation of solubilization capacity for poorly soluble drug ibuprofen revealed the critical importance of water-to-surfactant + cosurfactant ratio and penetration of oil at the interface.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Molecular Liquids",
title = "Phase behaviour, microstructure and ibuprofen solubilization capacity of pseudo-ternary nonionic microemulsions",
volume = "160",
number = "2",
pages = "81-87",
doi = "10.1016/j.molliq.2011.02.010"
}

Đekić, L., Primorac, M.,& Jocković, J.. (2011). Phase behaviour, microstructure and ibuprofen solubilization capacity of pseudo-ternary nonionic microemulsions. in Journal of Molecular Liquids
Elsevier Science BV, Amsterdam., 160(2), 81-87.
https://doi.org/10.1016/j.molliq.2011.02.010

Đekić L, Primorac M, Jocković J. Phase behaviour, microstructure and ibuprofen solubilization capacity of pseudo-ternary nonionic microemulsions. in Journal of Molecular Liquids. 2011;160(2):81-87.
doi:10.1016/j.molliq.2011.02.010 .

Đekić, Ljiljana, Primorac, Marija, Jocković, Jelena, "Phase behaviour, microstructure and ibuprofen solubilization capacity of pseudo-ternary nonionic microemulsions" in Journal of Molecular Liquids, 160, no. 2 (2011):81-87,
https://doi.org/10.1016/j.molliq.2011.02.010 . .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Ibrić, Svetlana
AU  - Jocković, Jelena
AU  - Parojčić, Jelena
AU  - Đurić, Zorica
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1444
AB  - Percolation theory is a mathematical tool that enables insight into characteristics of geometrically complex systems. Geometrical transition of solid dosage forms is followed by sudden changes in certain tablet characteristics (mechanical properties, drug release rate). The aim of the presented study is implementation of percolation theory concepts in hydrophilic matrix tablets characterization, by determination of the percolaction thresholds for key mechanical properties of matrix tablets as well as for drug release profiles. Hydrophilic matrix tablets have been formulated using polyethylene oxide polymers as matrix forming substances, diclofenac sodium as the model drug substance, as well as mycrocristaline cellulose as a tablet filler. Varying the excipient weight ratio and applied compression force, 18 formulations have been prepared using direct compression method. Compressibility and compactibility of the excipients hava been investigated, followed by characterization of matrix tablets tensile strenght. Dissolution test for diclofenac sodium matrix tablets has been conducted using rotating paddles method, and obtained drug release profiles have been analyzed using mathematical model. In order to estimate percolation thresholds changes in matrix tablets tensile strength and kinetic parameters of dissolution profiles were studied in aspect to changes in matrix tablets relative density i.e. volumetric ratio of matrix forming substance and initial porosity of matrix tablets. Obtained values for percolation thresholds, i.e. critical porosities for tensile strenghts are 22,57 % and 50,63 % for PEO WSR 1105 and PEO WSR Coagulant hydrophilic matrix tablets respectively. Percolation threshold for kinetic parameters of diclofenac sodium release profiles for PEO WSR 1105 matrix tablets is 20,86%. Obtained results indicate that percolation thresholds can be identified as critical formulations that are susceptible to sudden changes in mechanical properties and/or characteristics in drug release profiles following minor changes in formulation composition or process parameters.
AB  - Perkolaciona teorija je matematička alatka koja omogućava uvid u karakteristike geometrijski složenih sistema. Geometrijska tranzicija u čvrstim farmaceutskim oblicima je povezana sa naglim promenama određenih karakteristika tableta (mehaničke karakteristike, brzina rastvaranja lekovite supstance). Cilj rada je implementacija koncepata perkolacione teorije u karakterizaciji hidrofilnih matriks tableta, određivanjem perkolacionih pragova za ključne mehaničke karakteristike matriks tableta kao i za profile brzine rastvaranja lekovite supstance. Hidrofilne matriks tablete su izrađene sa polietilen oksidnim polimerima kao matriks-formirajućim materijalima, diklofenak-natrijumom kao lekovitom supstancom i mikrokristalnom celulozom kao sredstvom za dopunjavanje. Izrađeno je 18 formulacija variranjem masenog udela ekscipijenasa i primenjene sile kompresije, pri čemu su matriks tablete izrađene metodom direktne kompresije. Ispitana je kompresibilnost i kompaktibilnost ekscipijenasa, kao i zatezna čvrstoća izrađenih matriks tableta. Brzina rastvaranja diklofenak-natrijuma iz matriks tableta je ispitana u aparaturi sa rotirajućom lopaticom, a dobijeni profili su analizirani primenom matematičkog modela. Perkolacioni pragovi su određeni praćenjem promena u zateznoj čvrstoći matriks tableta i kinetičkim parametrima profila brzine rastvaranja lekovite supstance, u funkciji relativne gustine matriks tableta odnosno zapreminskog udela matriks-formirajuće supstance i poroziteta matriks tableta. Dobijene vrednosti perkolacionih pragova, tj. kritičnih poroziteta za zateznu čvrstoću iznose 22,57% odnosno 50,63% za PEO WSR 1105 i PEO WSR Coagulant hidrofilne matriks tablete. Perkolacioni prag za kinetičke parametre profila brzine rastvaranja diklofenak-natrijuma za PEO WSR 1105 hidrofilne matriks tablete iznosi 20,86 %. Dobijeni rezultati ukazuju na mogućnost identifikacije perkolacionih pragova kao kritičnih formulacija koje podležu naglim promenama karakteristika matriks tableta sa manjim promenama u sastavu formulacija ili parametara procesa izrade.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Application of the percolation theory in the formulation of pharmaceutical dosage forms: Hydrophilic matrix tablets
T1  - Primena perkolacione teorije u formulaciji farmaceutskih oblika - hidrofilne matriks tablete
VL  - 60
IS  - 6
SP  - 1219
EP  - 1236
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1444
ER  - 

@article{
author = "Petrović, Jelena and Ibrić, Svetlana and Jocković, Jelena and Parojčić, Jelena and Đurić, Zorica",
year = "2010",
abstract = "Percolation theory is a mathematical tool that enables insight into characteristics of geometrically complex systems. Geometrical transition of solid dosage forms is followed by sudden changes in certain tablet characteristics (mechanical properties, drug release rate). The aim of the presented study is implementation of percolation theory concepts in hydrophilic matrix tablets characterization, by determination of the percolaction thresholds for key mechanical properties of matrix tablets as well as for drug release profiles. Hydrophilic matrix tablets have been formulated using polyethylene oxide polymers as matrix forming substances, diclofenac sodium as the model drug substance, as well as mycrocristaline cellulose as a tablet filler. Varying the excipient weight ratio and applied compression force, 18 formulations have been prepared using direct compression method. Compressibility and compactibility of the excipients hava been investigated, followed by characterization of matrix tablets tensile strenght. Dissolution test for diclofenac sodium matrix tablets has been conducted using rotating paddles method, and obtained drug release profiles have been analyzed using mathematical model. In order to estimate percolation thresholds changes in matrix tablets tensile strength and kinetic parameters of dissolution profiles were studied in aspect to changes in matrix tablets relative density i.e. volumetric ratio of matrix forming substance and initial porosity of matrix tablets. Obtained values for percolation thresholds, i.e. critical porosities for tensile strenghts are 22,57 % and 50,63 % for PEO WSR 1105 and PEO WSR Coagulant hydrophilic matrix tablets respectively. Percolation threshold for kinetic parameters of diclofenac sodium release profiles for PEO WSR 1105 matrix tablets is 20,86%. Obtained results indicate that percolation thresholds can be identified as critical formulations that are susceptible to sudden changes in mechanical properties and/or characteristics in drug release profiles following minor changes in formulation composition or process parameters., Perkolaciona teorija je matematička alatka koja omogućava uvid u karakteristike geometrijski složenih sistema. Geometrijska tranzicija u čvrstim farmaceutskim oblicima je povezana sa naglim promenama određenih karakteristika tableta (mehaničke karakteristike, brzina rastvaranja lekovite supstance). Cilj rada je implementacija koncepata perkolacione teorije u karakterizaciji hidrofilnih matriks tableta, određivanjem perkolacionih pragova za ključne mehaničke karakteristike matriks tableta kao i za profile brzine rastvaranja lekovite supstance. Hidrofilne matriks tablete su izrađene sa polietilen oksidnim polimerima kao matriks-formirajućim materijalima, diklofenak-natrijumom kao lekovitom supstancom i mikrokristalnom celulozom kao sredstvom za dopunjavanje. Izrađeno je 18 formulacija variranjem masenog udela ekscipijenasa i primenjene sile kompresije, pri čemu su matriks tablete izrađene metodom direktne kompresije. Ispitana je kompresibilnost i kompaktibilnost ekscipijenasa, kao i zatezna čvrstoća izrađenih matriks tableta. Brzina rastvaranja diklofenak-natrijuma iz matriks tableta je ispitana u aparaturi sa rotirajućom lopaticom, a dobijeni profili su analizirani primenom matematičkog modela. Perkolacioni pragovi su određeni praćenjem promena u zateznoj čvrstoći matriks tableta i kinetičkim parametrima profila brzine rastvaranja lekovite supstance, u funkciji relativne gustine matriks tableta odnosno zapreminskog udela matriks-formirajuće supstance i poroziteta matriks tableta. Dobijene vrednosti perkolacionih pragova, tj. kritičnih poroziteta za zateznu čvrstoću iznose 22,57% odnosno 50,63% za PEO WSR 1105 i PEO WSR Coagulant hidrofilne matriks tablete. Perkolacioni prag za kinetičke parametre profila brzine rastvaranja diklofenak-natrijuma za PEO WSR 1105 hidrofilne matriks tablete iznosi 20,86 %. Dobijeni rezultati ukazuju na mogućnost identifikacije perkolacionih pragova kao kritičnih formulacija koje podležu naglim promenama karakteristika matriks tableta sa manjim promenama u sastavu formulacija ili parametara procesa izrade.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Application of the percolation theory in the formulation of pharmaceutical dosage forms: Hydrophilic matrix tablets, Primena perkolacione teorije u formulaciji farmaceutskih oblika - hidrofilne matriks tablete",
volume = "60",
number = "6",
pages = "1219-1236",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1444"
}

Petrović, J., Ibrić, S., Jocković, J., Parojčić, J.,& Đurić, Z.. (2010). Application of the percolation theory in the formulation of pharmaceutical dosage forms: Hydrophilic matrix tablets. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 60(6), 1219-1236.
https://hdl.handle.net/21.15107/rcub_farfar_1444

Petrović J, Ibrić S, Jocković J, Parojčić J, Đurić Z. Application of the percolation theory in the formulation of pharmaceutical dosage forms: Hydrophilic matrix tablets. in Arhiv za farmaciju. 2010;60(6):1219-1236.
https://hdl.handle.net/21.15107/rcub_farfar_1444 .

Petrović, Jelena, Ibrić, Svetlana, Jocković, Jelena, Parojčić, Jelena, Đurić, Zorica, "Application of the percolation theory in the formulation of pharmaceutical dosage forms: Hydrophilic matrix tablets" in Arhiv za farmaciju, 60, no. 6 (2010):1219-1236,
https://hdl.handle.net/21.15107/rcub_farfar_1444 .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Jocković, Jelena
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1193
AB  - Objectives The main objective of this study was to develop a mathematical model for the characterization of diclofenac sodium diffusion from polyethylene oxide (PEO) matrices. A model was developed on the basis of the diffusion theory accounting for the characteristics of the polymer: swelling with subsequent dissolution in water. The concentration-dependent diffusion of drug and water was taken into account. Experimental data were analysed using a computer software program as an aid for solving partial differential equations. Methods Six formulations of matrix tablets with different drug-excipient ratios were prepared using low-molecular-weight PEO as a matrix-forming material. For obtaining drug release data, dissolution studies were performed and water uptake by pure PEO matrices was studied as well. Key findings A good agreement of the developed model with experimental results was demonstrated. Some anomalies in drug diffusion were observed and their origin was questioned. Changes in the parameters characterizing the process of diffusion are attributed to glassy-rubbery polymer transitions. Additional interpretation of this phenomenon on the basis of percolation theory is also provided. Conclusions The obtained model has the ability to predict the required characteristics of matrices for desired drug release. The composition of batches with undesirable release properties can be predetermined and avoided in manufacturing.
PB  - Wiley-Blackwell Publishing, Inc, Malden
T2  - Journal of Pharmacy and Pharmacology
T1  - Modelling of diclofenac sodium diffusion from swellable and water-soluble polyethylene oxide matrices
VL  - 61
IS  - 11
SP  - 1449
EP  - 1456
DO  - 10.1211/jpp/61.11.0003
ER  - 

@article{
author = "Petrović, Jelena and Jocković, Jelena and Ibrić, Svetlana and Đurić, Zorica",
year = "2009",
abstract = "Objectives The main objective of this study was to develop a mathematical model for the characterization of diclofenac sodium diffusion from polyethylene oxide (PEO) matrices. A model was developed on the basis of the diffusion theory accounting for the characteristics of the polymer: swelling with subsequent dissolution in water. The concentration-dependent diffusion of drug and water was taken into account. Experimental data were analysed using a computer software program as an aid for solving partial differential equations. Methods Six formulations of matrix tablets with different drug-excipient ratios were prepared using low-molecular-weight PEO as a matrix-forming material. For obtaining drug release data, dissolution studies were performed and water uptake by pure PEO matrices was studied as well. Key findings A good agreement of the developed model with experimental results was demonstrated. Some anomalies in drug diffusion were observed and their origin was questioned. Changes in the parameters characterizing the process of diffusion are attributed to glassy-rubbery polymer transitions. Additional interpretation of this phenomenon on the basis of percolation theory is also provided. Conclusions The obtained model has the ability to predict the required characteristics of matrices for desired drug release. The composition of batches with undesirable release properties can be predetermined and avoided in manufacturing.",
publisher = "Wiley-Blackwell Publishing, Inc, Malden",
journal = "Journal of Pharmacy and Pharmacology",
title = "Modelling of diclofenac sodium diffusion from swellable and water-soluble polyethylene oxide matrices",
volume = "61",
number = "11",
pages = "1449-1456",
doi = "10.1211/jpp/61.11.0003"
}

Petrović, J., Jocković, J., Ibrić, S.,& Đurić, Z.. (2009). Modelling of diclofenac sodium diffusion from swellable and water-soluble polyethylene oxide matrices. in Journal of Pharmacy and Pharmacology
Wiley-Blackwell Publishing, Inc, Malden., 61(11), 1449-1456.
https://doi.org/10.1211/jpp/61.11.0003

Petrović J, Jocković J, Ibrić S, Đurić Z. Modelling of diclofenac sodium diffusion from swellable and water-soluble polyethylene oxide matrices. in Journal of Pharmacy and Pharmacology. 2009;61(11):1449-1456.
doi:10.1211/jpp/61.11.0003 .

Petrović, Jelena, Jocković, Jelena, Ibrić, Svetlana, Đurić, Zorica, "Modelling of diclofenac sodium diffusion from swellable and water-soluble polyethylene oxide matrices" in Journal of Pharmacy and Pharmacology, 61, no. 11 (2009):1449-1456,
https://doi.org/10.1211/jpp/61.11.0003 . .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Ibrić, Svetlana
AU  - Jocković, Jelena
AU  - Parojčić, Jelena
AU  - Đurić, Zorica
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1175
AB  - The purpose of this study was to implement the concepts of percolation theory in the characterization of drug release from hydrophilic matrix tablets. Percolation theory is a powerful statistical tool that enables mathematical insight into geometrically complex and disordered systems. Matrix tablets are effective substrate for the implementation of percolation theory because of their inherent disordered structure. The objective was to predict percolation thresholds of polyethylene oxide and polyacrylic polymers in diclofenac sodium hydrophilic matrices. Matrix tablets were prepared using polyethylene oxide or polyacrylic acid as matrix forming materials and diclofenac sodium was used as a model drug substance. Ten formulations with different drug/excipient ratios were prepared using the direct compression method. Dissolution studies were performed using the paddle apparatus method. For estimating percolation threshold the change of the kinetic parameters in aspect to the volumetric-fraction of excipient plus initial porosity of the tablets was studied. Observed critical points with sudden changes lit behavior of kinetic Parameters can be attributed to the percolation thresholds. Percolation threshold is found to be 60.22% v/v polyethylene oxide + initial porosity and 39.94% v/v polyacrylic acid + initial porosity. The results obtained demonstrate that percolation theory call be used to design and develop matrix tablet formulations. Determination of percolation threshold is a useful tool for preparing robust formulations.
PB  - Editions Sante, Paris
T2  - Journal of Drug Delivery Science and Technology
T1  - Determination of the percolation thresholds for polyethylene oxide and polyacrylic acid matrix tablets
VL  - 19
IS  - 5
SP  - 359
EP  - 364
DO  - 10.1016/S1773-2247(09)50074-3
ER  - 

@article{
author = "Petrović, Jelena and Ibrić, Svetlana and Jocković, Jelena and Parojčić, Jelena and Đurić, Zorica",
year = "2009",
abstract = "The purpose of this study was to implement the concepts of percolation theory in the characterization of drug release from hydrophilic matrix tablets. Percolation theory is a powerful statistical tool that enables mathematical insight into geometrically complex and disordered systems. Matrix tablets are effective substrate for the implementation of percolation theory because of their inherent disordered structure. The objective was to predict percolation thresholds of polyethylene oxide and polyacrylic polymers in diclofenac sodium hydrophilic matrices. Matrix tablets were prepared using polyethylene oxide or polyacrylic acid as matrix forming materials and diclofenac sodium was used as a model drug substance. Ten formulations with different drug/excipient ratios were prepared using the direct compression method. Dissolution studies were performed using the paddle apparatus method. For estimating percolation threshold the change of the kinetic parameters in aspect to the volumetric-fraction of excipient plus initial porosity of the tablets was studied. Observed critical points with sudden changes lit behavior of kinetic Parameters can be attributed to the percolation thresholds. Percolation threshold is found to be 60.22% v/v polyethylene oxide + initial porosity and 39.94% v/v polyacrylic acid + initial porosity. The results obtained demonstrate that percolation theory call be used to design and develop matrix tablet formulations. Determination of percolation threshold is a useful tool for preparing robust formulations.",
publisher = "Editions Sante, Paris",
journal = "Journal of Drug Delivery Science and Technology",
title = "Determination of the percolation thresholds for polyethylene oxide and polyacrylic acid matrix tablets",
volume = "19",
number = "5",
pages = "359-364",
doi = "10.1016/S1773-2247(09)50074-3"
}

Petrović, J., Ibrić, S., Jocković, J., Parojčić, J.,& Đurić, Z.. (2009). Determination of the percolation thresholds for polyethylene oxide and polyacrylic acid matrix tablets. in Journal of Drug Delivery Science and Technology
Editions Sante, Paris., 19(5), 359-364.
https://doi.org/10.1016/S1773-2247(09)50074-3

Petrović J, Ibrić S, Jocković J, Parojčić J, Đurić Z. Determination of the percolation thresholds for polyethylene oxide and polyacrylic acid matrix tablets. in Journal of Drug Delivery Science and Technology. 2009;19(5):359-364.
doi:10.1016/S1773-2247(09)50074-3 .

Petrović, Jelena, Ibrić, Svetlana, Jocković, Jelena, Parojčić, Jelena, Đurić, Zorica, "Determination of the percolation thresholds for polyethylene oxide and polyacrylic acid matrix tablets" in Journal of Drug Delivery Science and Technology, 19, no. 5 (2009):359-364,
https://doi.org/10.1016/S1773-2247(09)50074-3 . .

TY  - CONF
AU  - Petrović, Jelena
AU  - Jocković, Jelena
AU  - Ibrić, Svetlana
AU  - Parojčić, Jelena
AU  - Đurić, Zorica
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1036
PB  - Elsevier Science BV, Amsterdam
C3  - Journal of Controlled Release
T1  - Mathematical modeling of diclofenac sodium's release from polyethylene oxide matrices
VL  - 132
IS  - 3
DO  - 10.1016/j.jconrel.2008.09.029
ER  - 

@conference{
author = "Petrović, Jelena and Jocković, Jelena and Ibrić, Svetlana and Parojčić, Jelena and Đurić, Zorica",
year = "2008",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Controlled Release",
title = "Mathematical modeling of diclofenac sodium's release from polyethylene oxide matrices",
volume = "132",
number = "3",
doi = "10.1016/j.jconrel.2008.09.029"
}

Petrović, J., Jocković, J., Ibrić, S., Parojčić, J.,& Đurić, Z.. (2008). Mathematical modeling of diclofenac sodium's release from polyethylene oxide matrices. in Journal of Controlled Release
Elsevier Science BV, Amsterdam., 132(3).
https://doi.org/10.1016/j.jconrel.2008.09.029

Petrović J, Jocković J, Ibrić S, Parojčić J, Đurić Z. Mathematical modeling of diclofenac sodium's release from polyethylene oxide matrices. in Journal of Controlled Release. 2008;132(3).
doi:10.1016/j.jconrel.2008.09.029 .

Petrović, Jelena, Jocković, Jelena, Ibrić, Svetlana, Parojčić, Jelena, Đurić, Zorica, "Mathematical modeling of diclofenac sodium's release from polyethylene oxide matrices" in Journal of Controlled Release, 132, no. 3 (2008),
https://doi.org/10.1016/j.jconrel.2008.09.029 . .