TY  - JOUR
AU  - Đokić, Marija
AU  - Kachrimanis, Kyriakos
AU  - Solomun, Ljiljana
AU  - Đuriš, Jelena
AU  - Vasiljević, Dragana
AU  - Ibrić, Svetlana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2215
AB  - The aim of this investigation was to examine the effect of a jet-mill and spray-drying process on the physicochemical and aerodynamic dispersion properties of amiloride HCl particles. Micro-fine particles were prepared by a spiral air jet-mill Hosokawa 50 AS and Mini Spray-Dryer B-191. A 2(3-1) fractional factorial experimental design was implemented to screen three jet-mill process parameters. Possible changes in the physicochemical properties of the material due to spiral jet-milling were examined by the determination of the particle size distribution (PSI)), powder true density, powder flowability, diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) and scanning electron microscopy (SEM). The effect of different jet-milling parameters and the spray-drying process on the aerosol dispersion characteristics was examined with a cascade impactor with a preseparator using the Aerolizer (R) dry powder inhaler device (Novartis, Switzerland). The results show that small changes in the particle size within the 1 to 5 mu m range had an impact on the physicochemical and aerosol dispersion properties of jet-milled and spray-dried particles.
PB  - Elsevier Science BV, Amsterdam
T2  - Powder Technology
T1  - A study of jet-milling and spray-drying process for the physicochemical and aerodynamic dispersion properties of amiloride HCl
VL  - 262
SP  - 170
EP  - 176
DO  - 10.1016/j.powtec.2014.04.066
ER  - 

@article{
author = "Đokić, Marija and Kachrimanis, Kyriakos and Solomun, Ljiljana and Đuriš, Jelena and Vasiljević, Dragana and Ibrić, Svetlana",
year = "2014",
abstract = "The aim of this investigation was to examine the effect of a jet-mill and spray-drying process on the physicochemical and aerodynamic dispersion properties of amiloride HCl particles. Micro-fine particles were prepared by a spiral air jet-mill Hosokawa 50 AS and Mini Spray-Dryer B-191. A 2(3-1) fractional factorial experimental design was implemented to screen three jet-mill process parameters. Possible changes in the physicochemical properties of the material due to spiral jet-milling were examined by the determination of the particle size distribution (PSI)), powder true density, powder flowability, diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) and scanning electron microscopy (SEM). The effect of different jet-milling parameters and the spray-drying process on the aerosol dispersion characteristics was examined with a cascade impactor with a preseparator using the Aerolizer (R) dry powder inhaler device (Novartis, Switzerland). The results show that small changes in the particle size within the 1 to 5 mu m range had an impact on the physicochemical and aerosol dispersion properties of jet-milled and spray-dried particles.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Powder Technology",
title = "A study of jet-milling and spray-drying process for the physicochemical and aerodynamic dispersion properties of amiloride HCl",
volume = "262",
pages = "170-176",
doi = "10.1016/j.powtec.2014.04.066"
}

Đokić, M., Kachrimanis, K., Solomun, L., Đuriš, J., Vasiljević, D.,& Ibrić, S.. (2014). A study of jet-milling and spray-drying process for the physicochemical and aerodynamic dispersion properties of amiloride HCl. in Powder Technology
Elsevier Science BV, Amsterdam., 262, 170-176.
https://doi.org/10.1016/j.powtec.2014.04.066

Đokić M, Kachrimanis K, Solomun L, Đuriš J, Vasiljević D, Ibrić S. A study of jet-milling and spray-drying process for the physicochemical and aerodynamic dispersion properties of amiloride HCl. in Powder Technology. 2014;262:170-176.
doi:10.1016/j.powtec.2014.04.066 .

Đokić, Marija, Kachrimanis, Kyriakos, Solomun, Ljiljana, Đuriš, Jelena, Vasiljević, Dragana, Ibrić, Svetlana, "A study of jet-milling and spray-drying process for the physicochemical and aerodynamic dispersion properties of amiloride HCl" in Powder Technology, 262 (2014):170-176,
https://doi.org/10.1016/j.powtec.2014.04.066 . .

TY  - JOUR
AU  - Đokić, Marija
AU  - Đuriš, Jelena
AU  - Solomun, Ljiljana
AU  - Kachrimanis, Kyriakos
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2159
AB  - The purpose of this study was to investigate the influence of spiral jet-milling process on the physicochemical characteristics of alpha polymorphic active pharmaceutical ingredient, using Carbamazepine form III as a model drug, and taking into consideration Quality by Design (QbD) approach to pharmaceutical development. A 2((4-1)) factorial screening design was implemented to identify the spiral jet-milling process variables that significantly affect the particle size distribution of milled samples. Diameter of injector nozzles, diameter of ring nozzles and air pressure were selected for further analysis using a 2((3-1)) factorial experimental design. Particle size distribution of additional samples was determined, while physicochemical properties were examined by differential scanning calorimetry (DSC), hot-stage polarized microscopy (HSPM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and compared to those of un-milled drug. The gathered results shown that applied experimental design approach is capable to predict material behavior and could help in better understanding of material behavior during jet-milling process. Created design space (DS) provides assurance of product quality, expressed as the powder particle sizes lower than 5 mu m, as well as, in initial polymorph form existence after jet-milling through combination and interaction of input variables.
PB  - Inst Chemical Engineers, Rugby
T2  - Chemical Engineering Research & Design
T1  - The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach
VL  - 92
IS  - 3
SP  - 500
EP  - 508
DO  - 10.1016/j.cherd.2013.09.011
ER  - 

@article{
author = "Đokić, Marija and Đuriš, Jelena and Solomun, Ljiljana and Kachrimanis, Kyriakos and Đurić, Zorica and Ibrić, Svetlana",
year = "2014",
abstract = "The purpose of this study was to investigate the influence of spiral jet-milling process on the physicochemical characteristics of alpha polymorphic active pharmaceutical ingredient, using Carbamazepine form III as a model drug, and taking into consideration Quality by Design (QbD) approach to pharmaceutical development. A 2((4-1)) factorial screening design was implemented to identify the spiral jet-milling process variables that significantly affect the particle size distribution of milled samples. Diameter of injector nozzles, diameter of ring nozzles and air pressure were selected for further analysis using a 2((3-1)) factorial experimental design. Particle size distribution of additional samples was determined, while physicochemical properties were examined by differential scanning calorimetry (DSC), hot-stage polarized microscopy (HSPM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and compared to those of un-milled drug. The gathered results shown that applied experimental design approach is capable to predict material behavior and could help in better understanding of material behavior during jet-milling process. Created design space (DS) provides assurance of product quality, expressed as the powder particle sizes lower than 5 mu m, as well as, in initial polymorph form existence after jet-milling through combination and interaction of input variables.",
publisher = "Inst Chemical Engineers, Rugby",
journal = "Chemical Engineering Research & Design",
title = "The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach",
volume = "92",
number = "3",
pages = "500-508",
doi = "10.1016/j.cherd.2013.09.011"
}

Đokić, M., Đuriš, J., Solomun, L., Kachrimanis, K., Đurić, Z.,& Ibrić, S.. (2014). The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach. in Chemical Engineering Research & Design
Inst Chemical Engineers, Rugby., 92(3), 500-508.
https://doi.org/10.1016/j.cherd.2013.09.011

Đokić M, Đuriš J, Solomun L, Kachrimanis K, Đurić Z, Ibrić S. The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach. in Chemical Engineering Research & Design. 2014;92(3):500-508.
doi:10.1016/j.cherd.2013.09.011 .

Đokić, Marija, Đuriš, Jelena, Solomun, Ljiljana, Kachrimanis, Kyriakos, Đurić, Zorica, Ibrić, Svetlana, "The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach" in Chemical Engineering Research & Design, 92, no. 3 (2014):500-508,
https://doi.org/10.1016/j.cherd.2013.09.011 . .

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  - Solomun, Ljiljana
AU  - Ibrić, Svetlana
AU  - Pejanović, Vjera
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1588
AB  - Stability testing is carried out in several phases of new product development. The effect of various external factors on possible formulations, compatibility of active pharmaceutical ingredient, excipients and primary packaging material, is examined in early phases of development. Possible pathways of degradation are defined, and degradation rate is estimated by subjecting the products to different, extreme conditions. The results obtained during this phase of testing are used for defining the testing parameters in formal stability studies. Numerous guidelines, which define the testing parameters, are used in this phase of testing. The principal elements which are defined include testing conditions and testing frequency. An accelerated stability testing is carried out over a period of 6 months, whereby a product is exposed to the temperature exceeding the expected warehousing temperature, while a long-term stability testing is performed under the predicting storage conditions, and the length of testing corresponds to the envisaged shelf life. Photostability testing is carried out within a stress testing, and in certain cases, in use stability testing is carried out, whereby storage conditions and the period within which a product must be used after the first opening, i.e. reconstitution, are defined. Testing results are also used for establishing the final specifications of the quality of medicinal products, particularly from the aspect of degradation products (impurities). Various statistical methods and mathematical models, such as artificial neural networks, are used in results processing for the purpose of estimating the stability in a shorter period of time.
AB  - Ispitivanje stabilnosti realizuje se u više faza razvoja novog proizvoda. U ranim fazama razvoja ispituju se uticaji različitih spoljašnjih faktora (temperatura, vlaga, svetlost, kiseonik, mikroorganizmi) na potencijalne formulacije, kompatibilnost lekovite supstance, pomoćnih supstanci i kontaktne ambalaže. Kondicioniranjem proizvoda u različitim, ekstremnim uslovima, definišu se mogući putevi degradacije i predviđa brzina degradacije. Rezultati koji se dobiju u toku ove faze ispitivanja koriste se za definisanje parametara ispitivanja u formalnim studijama stabilnosti. U ovoj fazi ispitivanja, primenjuju se brojne smernice kojima se definišu parametri koji će se ispitivati. Osnovni elementi koji se definišu jesu uslovi ispitivanja i frekvenca ispitivanja. Ubrzano ispitivanje stabilnosti sprovodi se u trajanju od 6 meseci, pri čemu se proizvod izlaže temperaturi višoj od očekivane temperature skladištenja; dugotrajno ispitivanje se izvodi pod očekivanim uslovima čuvanja, a dužina ispitivanja se poklapa sa predviđenim rokom trajanja. U okviru stres ispitivanja se vrši i ispitivanje fotostabilnosti, a u pojedinim slučajevima, vrši se ispitivanje in use stabilnosti, pri čemu se definišu uslovi čuvanja i rok u kome se proizvod mora upotrebiti nakon prvog otvaranja, odnosno rekonstitucije. Rezultati ispitivanja koriste se i za postavljanje konačnih specifikacija kvaliteta lekova, posebno sa aspekta degradacionih proizvoda (nečistoća). U obradi rezultata koriste se različite statističke metode i matematički modeli, kao što su veštačke neuronske mreže, u cilju predviđanja stabilnosti u kraćem vremenskom roku.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Drug stability: Industry view
T1  - Stabilnost lekova - industrijski aspect
VL  - 61
IS  - 5
SP  - 449
EP  - 463
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1588
ER  - 

@article{
author = "Solomun, Ljiljana and Ibrić, Svetlana and Pejanović, Vjera",
year = "2011",
abstract = "Stability testing is carried out in several phases of new product development. The effect of various external factors on possible formulations, compatibility of active pharmaceutical ingredient, excipients and primary packaging material, is examined in early phases of development. Possible pathways of degradation are defined, and degradation rate is estimated by subjecting the products to different, extreme conditions. The results obtained during this phase of testing are used for defining the testing parameters in formal stability studies. Numerous guidelines, which define the testing parameters, are used in this phase of testing. The principal elements which are defined include testing conditions and testing frequency. An accelerated stability testing is carried out over a period of 6 months, whereby a product is exposed to the temperature exceeding the expected warehousing temperature, while a long-term stability testing is performed under the predicting storage conditions, and the length of testing corresponds to the envisaged shelf life. Photostability testing is carried out within a stress testing, and in certain cases, in use stability testing is carried out, whereby storage conditions and the period within which a product must be used after the first opening, i.e. reconstitution, are defined. Testing results are also used for establishing the final specifications of the quality of medicinal products, particularly from the aspect of degradation products (impurities). Various statistical methods and mathematical models, such as artificial neural networks, are used in results processing for the purpose of estimating the stability in a shorter period of time., Ispitivanje stabilnosti realizuje se u više faza razvoja novog proizvoda. U ranim fazama razvoja ispituju se uticaji različitih spoljašnjih faktora (temperatura, vlaga, svetlost, kiseonik, mikroorganizmi) na potencijalne formulacije, kompatibilnost lekovite supstance, pomoćnih supstanci i kontaktne ambalaže. Kondicioniranjem proizvoda u različitim, ekstremnim uslovima, definišu se mogući putevi degradacije i predviđa brzina degradacije. Rezultati koji se dobiju u toku ove faze ispitivanja koriste se za definisanje parametara ispitivanja u formalnim studijama stabilnosti. U ovoj fazi ispitivanja, primenjuju se brojne smernice kojima se definišu parametri koji će se ispitivati. Osnovni elementi koji se definišu jesu uslovi ispitivanja i frekvenca ispitivanja. Ubrzano ispitivanje stabilnosti sprovodi se u trajanju od 6 meseci, pri čemu se proizvod izlaže temperaturi višoj od očekivane temperature skladištenja; dugotrajno ispitivanje se izvodi pod očekivanim uslovima čuvanja, a dužina ispitivanja se poklapa sa predviđenim rokom trajanja. U okviru stres ispitivanja se vrši i ispitivanje fotostabilnosti, a u pojedinim slučajevima, vrši se ispitivanje in use stabilnosti, pri čemu se definišu uslovi čuvanja i rok u kome se proizvod mora upotrebiti nakon prvog otvaranja, odnosno rekonstitucije. Rezultati ispitivanja koriste se i za postavljanje konačnih specifikacija kvaliteta lekova, posebno sa aspekta degradacionih proizvoda (nečistoća). U obradi rezultata koriste se različite statističke metode i matematički modeli, kao što su veštačke neuronske mreže, u cilju predviđanja stabilnosti u kraćem vremenskom roku.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Drug stability: Industry view, Stabilnost lekova - industrijski aspect",
volume = "61",
number = "5",
pages = "449-463",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1588"
}

Solomun, L., Ibrić, S.,& Pejanović, V.. (2011). Drug stability: Industry view. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 61(5), 449-463.
https://hdl.handle.net/21.15107/rcub_farfar_1588

Solomun L, Ibrić S, Pejanović V. Drug stability: Industry view. in Arhiv za farmaciju. 2011;61(5):449-463.
https://hdl.handle.net/21.15107/rcub_farfar_1588 .

Solomun, Ljiljana, Ibrić, Svetlana, Pejanović, Vjera, "Drug stability: Industry view" in Arhiv za farmaciju, 61, no. 5 (2011):449-463,
https://hdl.handle.net/21.15107/rcub_farfar_1588 .

TY  - JOUR
AU  - Solomun, Ljiljana
AU  - Ibrić, Svetlana
AU  - Vajs, Vlatka
AU  - Vucković, Ivan M.
AU  - Vujić, Zorica
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1426
AB  - In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form, i.e., freeze-dried powder for injections, was examined. The goal was to evaluate the chemical stabilities of methylprednisolone sodium succinate packaged in a dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. The method proposed by United States Pharmacopeia was used to determine concentrations of methylprednisolone, as the sum of the concentration of methylprednisolone esters (17-hydrogen succinate and 21-hydrogen succinate) and free methylprednisolone. The HPLC method was used for stability evaluation of the active substance and determination of related substances. Four main degradation products were registered. Temperature has a major impact on the degradation process with the appearance of 3 degradation products (impurities B, C and D), while the presence of light caused an increasing content of impurity A. Identification of impurity B, C and D has been realized using mass and NMR spectroscopy. All three substances are substances related to methylprednisolone.
AB  - U ovom radu ispitivane su osobine farmakološki aktivne supstance metilprednizolona (u obliku metilprednizolon-natrijum-sukcinata) u gotovom proizvodu - liofilizatu za rastvor za injekcije. Cilj rada je ispitivanje hemijske stabilnosti metilpredni-zolon-natrijum-sukcinata u dvokomornoj bočici, kao specifičnom sistemu kontaktnog pakovanja. Ispitan je efekat različitih parametara: temperature, vlage i svetlosti. Za određivanje koncentracije metilprednizolona, kao zbirne koncentracije metilprednizolon estara (17-hidrogen-sukcinata i 21-hidrogen-sukcinata) i slobodnog metilprednizolona, korišćena je metoda opisana u Američkoj farmakopeji. Za ispitivanje srodnih supstanci primenjena je HPLC metoda. Uočena su 4 degradaciona proizvoda. Dokazano je da povećanje temperature ima najveći značaj na proces degradacije i utiče na povećanje sadržaja nečistoća B, C i D, dok prisustvo svetlosti dovodi do povećanja sadržaja nečistoće A. Nečistoće B, C i D su identifikovane primenom masene i NMR spektroskopije. Sve tri nečistoće su identifikovane kao srodne supstance metilprednizolona.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Methylprednisolone and its related substances in freeze-dried powders for injections
T1  - Metilprednizolon i njegove srodne supstance u liofilizatu za rastvor za injekcije
VL  - 75
IS  - 10
SP  - 1441
EP  - 1452
DO  - 10.2298/JSC100115087S
ER  - 

@article{
author = "Solomun, Ljiljana and Ibrić, Svetlana and Vajs, Vlatka and Vucković, Ivan M. and Vujić, Zorica",
year = "2010",
abstract = "In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form, i.e., freeze-dried powder for injections, was examined. The goal was to evaluate the chemical stabilities of methylprednisolone sodium succinate packaged in a dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. The method proposed by United States Pharmacopeia was used to determine concentrations of methylprednisolone, as the sum of the concentration of methylprednisolone esters (17-hydrogen succinate and 21-hydrogen succinate) and free methylprednisolone. The HPLC method was used for stability evaluation of the active substance and determination of related substances. Four main degradation products were registered. Temperature has a major impact on the degradation process with the appearance of 3 degradation products (impurities B, C and D), while the presence of light caused an increasing content of impurity A. Identification of impurity B, C and D has been realized using mass and NMR spectroscopy. All three substances are substances related to methylprednisolone., U ovom radu ispitivane su osobine farmakološki aktivne supstance metilprednizolona (u obliku metilprednizolon-natrijum-sukcinata) u gotovom proizvodu - liofilizatu za rastvor za injekcije. Cilj rada je ispitivanje hemijske stabilnosti metilpredni-zolon-natrijum-sukcinata u dvokomornoj bočici, kao specifičnom sistemu kontaktnog pakovanja. Ispitan je efekat različitih parametara: temperature, vlage i svetlosti. Za određivanje koncentracije metilprednizolona, kao zbirne koncentracije metilprednizolon estara (17-hidrogen-sukcinata i 21-hidrogen-sukcinata) i slobodnog metilprednizolona, korišćena je metoda opisana u Američkoj farmakopeji. Za ispitivanje srodnih supstanci primenjena je HPLC metoda. Uočena su 4 degradaciona proizvoda. Dokazano je da povećanje temperature ima najveći značaj na proces degradacije i utiče na povećanje sadržaja nečistoća B, C i D, dok prisustvo svetlosti dovodi do povećanja sadržaja nečistoće A. Nečistoće B, C i D su identifikovane primenom masene i NMR spektroskopije. Sve tri nečistoće su identifikovane kao srodne supstance metilprednizolona.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Methylprednisolone and its related substances in freeze-dried powders for injections, Metilprednizolon i njegove srodne supstance u liofilizatu za rastvor za injekcije",
volume = "75",
number = "10",
pages = "1441-1452",
doi = "10.2298/JSC100115087S"
}

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

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

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

TY  - JOUR
AU  - Solomun, Ljiljana
AU  - Ibrić, Svetlana
AU  - Boltić, Zorana
AU  - Đurić, Zorica
AU  - Stupar, Biljana
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1024
AB  - The unique approach in manufacturing of pharmaceutical dosage forms of active substances known to be unstable in aqueous solution is the introduction of lyophilization process. Nevertheless, these products must be reconstituted using the diluent from a separate container before application. The possible solution for this problem is the application of dual chamber vials comprising the freeze-dried product in a lower compartment of the vial and the solution for reconstitution in the upper chamber. The main issue in development of such product is the choice of contact packaging (rubber closures, glass vials and the container closure system as a whole). The most important parameter used for evaluation of the influence of contact material on product quality was the pH value. The results have shown that the type of vials (moulded or tubular glass) has no impact on pH shift of the solution for reconstitution (tested solution-TS), while significant differences in pH value of the TS were observed depending on the rubber closures formulation used (with some formulations, the pH shift during the test was 6.5-9.14). Benzyl alcohol assay during the tests remained unchanged. Integrity tests of the container closure system (CCS) have demonstrated the adequacy of the selected packaging system. The quality of the CCS of choice was confirmed in the course of stability studies, only parameters directly influenced by CCS being presented in this work: loss on drying and pH value. On the basis of these results, no changes in loss on drying were connected to CCS, and the pH value of the reconstituted solution remains unchanged in samples tested both ex-tempore and after in-use period of 48 h.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - The impact of primary packaging on the quality of parenteral products
VL  - 48
IS  - 3
SP  - 744
EP  - 748
DO  - 10.1016/j.jpba.2008.07.025
ER  - 

@article{
author = "Solomun, Ljiljana and Ibrić, Svetlana and Boltić, Zorana and Đurić, Zorica and Stupar, Biljana",
year = "2008",
abstract = "The unique approach in manufacturing of pharmaceutical dosage forms of active substances known to be unstable in aqueous solution is the introduction of lyophilization process. Nevertheless, these products must be reconstituted using the diluent from a separate container before application. The possible solution for this problem is the application of dual chamber vials comprising the freeze-dried product in a lower compartment of the vial and the solution for reconstitution in the upper chamber. The main issue in development of such product is the choice of contact packaging (rubber closures, glass vials and the container closure system as a whole). The most important parameter used for evaluation of the influence of contact material on product quality was the pH value. The results have shown that the type of vials (moulded or tubular glass) has no impact on pH shift of the solution for reconstitution (tested solution-TS), while significant differences in pH value of the TS were observed depending on the rubber closures formulation used (with some formulations, the pH shift during the test was 6.5-9.14). Benzyl alcohol assay during the tests remained unchanged. Integrity tests of the container closure system (CCS) have demonstrated the adequacy of the selected packaging system. The quality of the CCS of choice was confirmed in the course of stability studies, only parameters directly influenced by CCS being presented in this work: loss on drying and pH value. On the basis of these results, no changes in loss on drying were connected to CCS, and the pH value of the reconstituted solution remains unchanged in samples tested both ex-tempore and after in-use period of 48 h.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "The impact of primary packaging on the quality of parenteral products",
volume = "48",
number = "3",
pages = "744-748",
doi = "10.1016/j.jpba.2008.07.025"
}

Solomun, L., Ibrić, S., Boltić, Z., Đurić, Z.,& Stupar, B.. (2008). The impact of primary packaging on the quality of parenteral products. in Journal of Pharmaceutical and Biomedical Analysis
Pergamon-Elsevier Science Ltd, Oxford., 48(3), 744-748.
https://doi.org/10.1016/j.jpba.2008.07.025

Solomun L, Ibrić S, Boltić Z, Đurić Z, Stupar B. The impact of primary packaging on the quality of parenteral products. in Journal of Pharmaceutical and Biomedical Analysis. 2008;48(3):744-748.
doi:10.1016/j.jpba.2008.07.025 .

Solomun, Ljiljana, Ibrić, Svetlana, Boltić, Zorana, Đurić, Zorica, Stupar, Biljana, "The impact of primary packaging on the quality of parenteral products" in Journal of Pharmaceutical and Biomedical Analysis, 48, no. 3 (2008):744-748,
https://doi.org/10.1016/j.jpba.2008.07.025 . .

TY  - JOUR
AU  - Ibrić, Svetlana
AU  - Jovanović, Milica
AU  - Đurić, Zorica
AU  - Parojčić, Jelena
AU  - Solomun, Ljiljana
AU  - Lucić, Branka
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/922
AB  - This study had two aims. Firstly, we wanted to model the effects of the percentage of Eudragit RS PO and compression pressure as the most important process and formulation variables on the time course of drug release from extended-release matrix aspirin tablets. Secondly, we investigated the possibility of predicting drug stability and shelf-life using an artificial neural network (ANN). Ten types of matrix aspirin tablets were prepared as model formulations and were stored in stability chambers at 60 degrees C, 50 degrees C, 40 degrees C and 30 degrees C and controlled humidity. Samples were removed at predefined time points and analysed for acetylsalicylic acid (ASA) and salicylic acid (SA) content using stability-indicating HPLC. The decrease in aspirin content followed apparent zero-order kinetics. The amount of Eudragit RS PO and compression pressure were selected as causal factors. The apparent zero-order rate constants for each temperature were chosen as output variables for the ANN. A set of output parameters and causal factors were used as training data for the generalized regression neural network (GRNN). For two additional test formulations, Arrhenius plots were constructed from the experimentally observed and GRNN-predicted results. The slopes of experimentally observed and predicted Arrhenius plots were tested for significance using Student's t-test. For test formulations, the shelf life (t(95%)) was then calculated from experimentally observed values (t(95%) 82.90 weeks), as well as from GRNN-predicted values (t(95%) 81.88 weeks). These results demonstrate that GRNN networks can be used to predict ASA content and shelf life without stability testing for formulations in which the amount of polymer and tablet hardness are within the investigated range.
PB  - Pharmaceutical Press-Royal Pharmaceutical Soc Great Britian, London
T2  - Journal of Pharmacy and Pharmacology
T1  - Generalized regression neural networks in prediction of drug stability
VL  - 59
IS  - 5
SP  - 745
EP  - 750
DO  - 10.1211/jpp.59.5.0017
ER  - 

@article{
author = "Ibrić, Svetlana and Jovanović, Milica and Đurić, Zorica and Parojčić, Jelena and Solomun, Ljiljana and Lucić, Branka",
year = "2007",
abstract = "This study had two aims. Firstly, we wanted to model the effects of the percentage of Eudragit RS PO and compression pressure as the most important process and formulation variables on the time course of drug release from extended-release matrix aspirin tablets. Secondly, we investigated the possibility of predicting drug stability and shelf-life using an artificial neural network (ANN). Ten types of matrix aspirin tablets were prepared as model formulations and were stored in stability chambers at 60 degrees C, 50 degrees C, 40 degrees C and 30 degrees C and controlled humidity. Samples were removed at predefined time points and analysed for acetylsalicylic acid (ASA) and salicylic acid (SA) content using stability-indicating HPLC. The decrease in aspirin content followed apparent zero-order kinetics. The amount of Eudragit RS PO and compression pressure were selected as causal factors. The apparent zero-order rate constants for each temperature were chosen as output variables for the ANN. A set of output parameters and causal factors were used as training data for the generalized regression neural network (GRNN). For two additional test formulations, Arrhenius plots were constructed from the experimentally observed and GRNN-predicted results. The slopes of experimentally observed and predicted Arrhenius plots were tested for significance using Student's t-test. For test formulations, the shelf life (t(95%)) was then calculated from experimentally observed values (t(95%) 82.90 weeks), as well as from GRNN-predicted values (t(95%) 81.88 weeks). These results demonstrate that GRNN networks can be used to predict ASA content and shelf life without stability testing for formulations in which the amount of polymer and tablet hardness are within the investigated range.",
publisher = "Pharmaceutical Press-Royal Pharmaceutical Soc Great Britian, London",
journal = "Journal of Pharmacy and Pharmacology",
title = "Generalized regression neural networks in prediction of drug stability",
volume = "59",
number = "5",
pages = "745-750",
doi = "10.1211/jpp.59.5.0017"
}

Ibrić, S., Jovanović, M., Đurić, Z., Parojčić, J., Solomun, L.,& Lucić, B.. (2007). Generalized regression neural networks in prediction of drug stability. in Journal of Pharmacy and Pharmacology
Pharmaceutical Press-Royal Pharmaceutical Soc Great Britian, London., 59(5), 745-750.
https://doi.org/10.1211/jpp.59.5.0017

Ibrić S, Jovanović M, Đurić Z, Parojčić J, Solomun L, Lucić B. Generalized regression neural networks in prediction of drug stability. in Journal of Pharmacy and Pharmacology. 2007;59(5):745-750.
doi:10.1211/jpp.59.5.0017 .

Ibrić, Svetlana, Jovanović, Milica, Đurić, Zorica, Parojčić, Jelena, Solomun, Ljiljana, Lucić, Branka, "Generalized regression neural networks in prediction of drug stability" in Journal of Pharmacy and Pharmacology, 59, no. 5 (2007):745-750,
https://doi.org/10.1211/jpp.59.5.0017 . .

TY  - JOUR
AU  - Živanović, L
AU  - Ivanović, I
AU  - Solomun, Ljiljana
AU  - Zečević, Mira
PY  - 2004
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/510
AB  - Cefuroxime is a broad-spectrum second-generation bactericidal cephalosporin antibiotic active against beta-lactamose-producing strains. Anti-cefuroxime, the geometric isomer of cefuroxime, might be present in cefuroxime dosage forms as a process-related impurity and possible degradation product. In the work discussed in this paper a precise and sensitive micellar liquid chromatographic (MLC) method for stability testing of cefuroxime axetil and anti-cefuroxime axetil in tablets, using benzoic acid as internal standard, was developed and validated. MLC was performed on an XTerra C-18 reversed-phase column at 50 degreesC with 8:92 (v/v) acetonitrile-20 mm sodium dodecyl sulphate, pH 2.5, as mobile phase at a flow rate of 1.5 mL min(-1). Detection was at 280 nm. Under these conditions the retention time and retention factor were of 6.65 min and 4.57, respectively, for cefuroxime axetil and 11.45 min and 8.59, respectively, for anti-cefuroxime axetil, indicating that the compounds were well separated. RSD values for quantification of cefuroxime axetil and anti-cefuroxime axetil were 0.39 and 1.7%, respectively, indicating the precision of the MLC method was good. The method is sensitive-LOD = 0.5 mug mL(-1) and LOQ = 1.5 mug mL(-1) for anti-cefuroxime axetil-and reproducible, with good recovery values.
PB  - Springer Heidelberg, Heidelberg
T2  - Chromatographia
T1  - Stability testing of cefuroxime in tablets by micellar liquid chromatography
VL  - 60
IS  - SUPPL.
DO  - 10.1365/s10337-004-0237-5
ER  - 

@article{
author = "Živanović, L and Ivanović, I and Solomun, Ljiljana and Zečević, Mira",
year = "2004",
abstract = "Cefuroxime is a broad-spectrum second-generation bactericidal cephalosporin antibiotic active against beta-lactamose-producing strains. Anti-cefuroxime, the geometric isomer of cefuroxime, might be present in cefuroxime dosage forms as a process-related impurity and possible degradation product. In the work discussed in this paper a precise and sensitive micellar liquid chromatographic (MLC) method for stability testing of cefuroxime axetil and anti-cefuroxime axetil in tablets, using benzoic acid as internal standard, was developed and validated. MLC was performed on an XTerra C-18 reversed-phase column at 50 degreesC with 8:92 (v/v) acetonitrile-20 mm sodium dodecyl sulphate, pH 2.5, as mobile phase at a flow rate of 1.5 mL min(-1). Detection was at 280 nm. Under these conditions the retention time and retention factor were of 6.65 min and 4.57, respectively, for cefuroxime axetil and 11.45 min and 8.59, respectively, for anti-cefuroxime axetil, indicating that the compounds were well separated. RSD values for quantification of cefuroxime axetil and anti-cefuroxime axetil were 0.39 and 1.7%, respectively, indicating the precision of the MLC method was good. The method is sensitive-LOD = 0.5 mug mL(-1) and LOQ = 1.5 mug mL(-1) for anti-cefuroxime axetil-and reproducible, with good recovery values.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Chromatographia",
title = "Stability testing of cefuroxime in tablets by micellar liquid chromatography",
volume = "60",
number = "SUPPL.",
doi = "10.1365/s10337-004-0237-5"
}

Živanović, L., Ivanović, I., Solomun, L.,& Zečević, M.. (2004). Stability testing of cefuroxime in tablets by micellar liquid chromatography. in Chromatographia
Springer Heidelberg, Heidelberg., 60(SUPPL.).
https://doi.org/10.1365/s10337-004-0237-5

Živanović L, Ivanović I, Solomun L, Zečević M. Stability testing of cefuroxime in tablets by micellar liquid chromatography. in Chromatographia. 2004;60(SUPPL.).
doi:10.1365/s10337-004-0237-5 .

Živanović, L, Ivanović, I, Solomun, Ljiljana, Zečević, Mira, "Stability testing of cefuroxime in tablets by micellar liquid chromatography" in Chromatographia, 60, no. SUPPL. (2004),
https://doi.org/10.1365/s10337-004-0237-5 . .

TY  - JOUR
AU  - Ibrić, Svetlana
AU  - Jovanović, M
AU  - Đurić, Zorica
AU  - Parojčić, Jelena
AU  - Petrović, Slobodan D.
AU  - Solomun, Ljiljana
AU  - Stupar, Biljana
PY  - 2003
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/469
AB  - The purpose of the present study was to model the effects of the concentration of Eudragit L 100 and compression pressure as the most important process and formulation variables on the in vitro release profile of aspirin from matrix tablets formulated with Eudragit L 100 as matrix substance and to optimize the formulation by artificial neural network. As model formulations, 10 kinds of aspirin matrix tablets were prepared. The amount of Eudragit L 100 and the compression pressure were selected as causal factors. In vitro dissolution time profiles at 4 different sampling times were chosen as responses. A set of release parameters and causal factors were used as tutorial data for the generalized regression neural network (GRNN) and analyzed using a computer. Observed results of drug release studies indicate that drug release rates vary widely between investigated formulations, with a range of 5 hours to more than 10 hours to complete dissolution. The GRNN model was optimized. The root mean square value for the trained network was 1.12%, which indicated that the optimal GRNN model was reached. Applying the generalized distance function method, the optimal tablet formulation predicted by GRNN was with 5% of Eudragit L 100 and tablet hardness 60N. Calculated difference (f1 2.465) and similarity (f2 85.61) factors indicate that there is no difference between predicted and experimentally observed drug release profiles for the optimal formulation. This work illustrates the potential for an artificial neural network, GRNN, to assist in development of extended release dosage forms.
PB  - AAPS PharmSci Editorial Office
T2  - AAPS PharmSciTech
T1  - Artificial neural networks in the modeling and optimization of aspirin extended release tablets with Eudragit L 100 as matrix substance
VL  - 4
IS  - 1
DO  - 10.1208/pt040109
ER  - 

@article{
author = "Ibrić, Svetlana and Jovanović, M and Đurić, Zorica and Parojčić, Jelena and Petrović, Slobodan D. and Solomun, Ljiljana and Stupar, Biljana",
year = "2003",
abstract = "The purpose of the present study was to model the effects of the concentration of Eudragit L 100 and compression pressure as the most important process and formulation variables on the in vitro release profile of aspirin from matrix tablets formulated with Eudragit L 100 as matrix substance and to optimize the formulation by artificial neural network. As model formulations, 10 kinds of aspirin matrix tablets were prepared. The amount of Eudragit L 100 and the compression pressure were selected as causal factors. In vitro dissolution time profiles at 4 different sampling times were chosen as responses. A set of release parameters and causal factors were used as tutorial data for the generalized regression neural network (GRNN) and analyzed using a computer. Observed results of drug release studies indicate that drug release rates vary widely between investigated formulations, with a range of 5 hours to more than 10 hours to complete dissolution. The GRNN model was optimized. The root mean square value for the trained network was 1.12%, which indicated that the optimal GRNN model was reached. Applying the generalized distance function method, the optimal tablet formulation predicted by GRNN was with 5% of Eudragit L 100 and tablet hardness 60N. Calculated difference (f1 2.465) and similarity (f2 85.61) factors indicate that there is no difference between predicted and experimentally observed drug release profiles for the optimal formulation. This work illustrates the potential for an artificial neural network, GRNN, to assist in development of extended release dosage forms.",
publisher = "AAPS PharmSci Editorial Office",
journal = "AAPS PharmSciTech",
title = "Artificial neural networks in the modeling and optimization of aspirin extended release tablets with Eudragit L 100 as matrix substance",
volume = "4",
number = "1",
doi = "10.1208/pt040109"
}

Ibrić, S., Jovanović, M., Đurić, Z., Parojčić, J., Petrović, S. D., Solomun, L.,& Stupar, B.. (2003). Artificial neural networks in the modeling and optimization of aspirin extended release tablets with Eudragit L 100 as matrix substance. in AAPS PharmSciTech
AAPS PharmSci Editorial Office., 4(1).
https://doi.org/10.1208/pt040109

Ibrić S, Jovanović M, Đurić Z, Parojčić J, Petrović SD, Solomun L, Stupar B. Artificial neural networks in the modeling and optimization of aspirin extended release tablets with Eudragit L 100 as matrix substance. in AAPS PharmSciTech. 2003;4(1).
doi:10.1208/pt040109 .

Ibrić, Svetlana, Jovanović, M, Đurić, Zorica, Parojčić, Jelena, Petrović, Slobodan D., Solomun, Ljiljana, Stupar, Biljana, "Artificial neural networks in the modeling and optimization of aspirin extended release tablets with Eudragit L 100 as matrix substance" in AAPS PharmSciTech, 4, no. 1 (2003),
https://doi.org/10.1208/pt040109 . .

TY  - CONF
AU  - Solomun, Ljiljana
AU  - Cvetićanin-Ilić, S.
AU  - Stupar, Biljana
AU  - Aćimović, D.
AU  - Jovanović, M.
PY  - 2002
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/409
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju
T1  - Photostability of drugs - nifedipine
T1  - Fotostabilnost lekova - nifedipin
VL  - 52
IS  - 4
SP  - 538
EP  - 539
UR  - https://hdl.handle.net/21.15107/rcub_farfar_409
ER  - 

@conference{
author = "Solomun, Ljiljana and Cvetićanin-Ilić, S. and Stupar, Biljana and Aćimović, D. and Jovanović, M.",
year = "2002",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Photostability of drugs - nifedipine, Fotostabilnost lekova - nifedipin",
volume = "52",
number = "4",
pages = "538-539",
url = "https://hdl.handle.net/21.15107/rcub_farfar_409"
}

Solomun, L., Cvetićanin-Ilić, S., Stupar, B., Aćimović, D.,& Jovanović, M.. (2002). Photostability of drugs - nifedipine. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 52(4), 538-539.
https://hdl.handle.net/21.15107/rcub_farfar_409

Solomun L, Cvetićanin-Ilić S, Stupar B, Aćimović D, Jovanović M. Photostability of drugs - nifedipine. in Arhiv za farmaciju. 2002;52(4):538-539.
https://hdl.handle.net/21.15107/rcub_farfar_409 .

Solomun, Ljiljana, Cvetićanin-Ilić, S., Stupar, Biljana, Aćimović, D., Jovanović, M., "Photostability of drugs - nifedipine" in Arhiv za farmaciju, 52, no. 4 (2002):538-539,
https://hdl.handle.net/21.15107/rcub_farfar_409 .

TY  - JOUR
AU  - Ibrić, Svetlana
AU  - Jovanović, M
AU  - Đurić, Zorica
AU  - Parojčić, Jelena
AU  - Solomun, Ljiljana
PY  - 2002
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/321
AB  - The objective of this work is to use a generalized regression neural network (GRNN) in the design of extended-release aspirin tablets. As model formulations, 10 kinds of aspirin matrix tablets were prepared. Eudragit((R)) RS PO was used as matrix substance. The amount of Eudragit((R)) RS PO and compression pressure were selected as causal factors. In-vitro dissolution-time profiles at four different sampling times, as well as coefficients n (release order) and log k (release constant) from the Peppas equation were estimated as release parameters. A set of release parameters and causal factors were used as tutorial data for the GRNN and analyzing using a computer. A GRNN model was constructed. The optimized GRNN model was used for prediction of formulation with desired in vitro drug release. For two tested formulations there was very good agreement between the GRNN predicted and observed in vitro profiles and estimated coefficients. Calculated difference (f(1)) and similarity (f(2)) factors indicate that there is no difference between predicted and experimental observed drug release profiles. This work illustrates the potential for an artificial neural network, GRNN, to assist in development of extended-release dosage forms. This method can be employed to achieve a desired in vitro dissolution profile.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Controlled Release
T1  - The application of generalized regression neural network in the modeling and optimization of aspirin extended release tablets with Eudragit (R) RS PO as matrix substance
VL  - 82
IS  - 2-3
SP  - 213
EP  - 222
DO  - 10.1016/S0168-3659(02)00044-5
ER  - 

@article{
author = "Ibrić, Svetlana and Jovanović, M and Đurić, Zorica and Parojčić, Jelena and Solomun, Ljiljana",
year = "2002",
abstract = "The objective of this work is to use a generalized regression neural network (GRNN) in the design of extended-release aspirin tablets. As model formulations, 10 kinds of aspirin matrix tablets were prepared. Eudragit((R)) RS PO was used as matrix substance. The amount of Eudragit((R)) RS PO and compression pressure were selected as causal factors. In-vitro dissolution-time profiles at four different sampling times, as well as coefficients n (release order) and log k (release constant) from the Peppas equation were estimated as release parameters. A set of release parameters and causal factors were used as tutorial data for the GRNN and analyzing using a computer. A GRNN model was constructed. The optimized GRNN model was used for prediction of formulation with desired in vitro drug release. For two tested formulations there was very good agreement between the GRNN predicted and observed in vitro profiles and estimated coefficients. Calculated difference (f(1)) and similarity (f(2)) factors indicate that there is no difference between predicted and experimental observed drug release profiles. This work illustrates the potential for an artificial neural network, GRNN, to assist in development of extended-release dosage forms. This method can be employed to achieve a desired in vitro dissolution profile.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Controlled Release",
title = "The application of generalized regression neural network in the modeling and optimization of aspirin extended release tablets with Eudragit (R) RS PO as matrix substance",
volume = "82",
number = "2-3",
pages = "213-222",
doi = "10.1016/S0168-3659(02)00044-5"
}

Ibrić, S., Jovanović, M., Đurić, Z., Parojčić, J.,& Solomun, L.. (2002). The application of generalized regression neural network in the modeling and optimization of aspirin extended release tablets with Eudragit (R) RS PO as matrix substance. in Journal of Controlled Release
Elsevier Science BV, Amsterdam., 82(2-3), 213-222.
https://doi.org/10.1016/S0168-3659(02)00044-5

Ibrić S, Jovanović M, Đurić Z, Parojčić J, Solomun L. The application of generalized regression neural network in the modeling and optimization of aspirin extended release tablets with Eudragit (R) RS PO as matrix substance. in Journal of Controlled Release. 2002;82(2-3):213-222.
doi:10.1016/S0168-3659(02)00044-5 .

Ibrić, Svetlana, Jovanović, M, Đurić, Zorica, Parojčić, Jelena, Solomun, Ljiljana, "The application of generalized regression neural network in the modeling and optimization of aspirin extended release tablets with Eudragit (R) RS PO as matrix substance" in Journal of Controlled Release, 82, no. 2-3 (2002):213-222,
https://doi.org/10.1016/S0168-3659(02)00044-5 . .

TY  - CONF
AU  - Agbaba, Danica
AU  - Solomun, Ljiljana
AU  - Živanov-Stakić, Dobrila
PY  - 1997
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/162
PB  - Akademiai Kiado Rt.
C3  - Journal of Planar Chromatography - Modern TLC
T1  - Simultaneous HPTLC determination of diltiazem and its impurity desacetyldiltiazem in raw material and in dosage forms
VL  - 10
IS  - 4
SP  - 303
EP  - 304
UR  - https://hdl.handle.net/21.15107/rcub_farfar_162
ER  - 

@conference{
author = "Agbaba, Danica and Solomun, Ljiljana and Živanov-Stakić, Dobrila",
year = "1997",
publisher = "Akademiai Kiado Rt.",
journal = "Journal of Planar Chromatography - Modern TLC",
title = "Simultaneous HPTLC determination of diltiazem and its impurity desacetyldiltiazem in raw material and in dosage forms",
volume = "10",
number = "4",
pages = "303-304",
url = "https://hdl.handle.net/21.15107/rcub_farfar_162"
}

Agbaba, D., Solomun, L.,& Živanov-Stakić, D.. (1997). Simultaneous HPTLC determination of diltiazem and its impurity desacetyldiltiazem in raw material and in dosage forms. in Journal of Planar Chromatography - Modern TLC
Akademiai Kiado Rt.., 10(4), 303-304.
https://hdl.handle.net/21.15107/rcub_farfar_162

Agbaba D, Solomun L, Živanov-Stakić D. Simultaneous HPTLC determination of diltiazem and its impurity desacetyldiltiazem in raw material and in dosage forms. in Journal of Planar Chromatography - Modern TLC. 1997;10(4):303-304.
https://hdl.handle.net/21.15107/rcub_farfar_162 .

Agbaba, Danica, Solomun, Ljiljana, Živanov-Stakić, Dobrila, "Simultaneous HPTLC determination of diltiazem and its impurity desacetyldiltiazem in raw material and in dosage forms" in Journal of Planar Chromatography - Modern TLC, 10, no. 4 (1997):303-304,
https://hdl.handle.net/21.15107/rcub_farfar_162 .

TY  - JOUR
AU  - Živanov-Stakić, Dobrila
AU  - Solomun, Ljiljana
AU  - Živanović, Ljiljana
PY  - 1990
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/68
T2  - Acta Pharmaceutica Hungarica
T1  - Spectrophotometric determination of tilidine using bromocresol green and bromophenol blue
VL  - 60
IS  - 5-6
SP  - 179
EP  - 181
UR  - https://hdl.handle.net/21.15107/rcub_farfar_68
ER  - 

@article{
author = "Živanov-Stakić, Dobrila and Solomun, Ljiljana and Živanović, Ljiljana",
year = "1990",
journal = "Acta Pharmaceutica Hungarica",
title = "Spectrophotometric determination of tilidine using bromocresol green and bromophenol blue",
volume = "60",
number = "5-6",
pages = "179-181",
url = "https://hdl.handle.net/21.15107/rcub_farfar_68"
}

Živanov-Stakić, D., Solomun, L.,& Živanović, L.. (1990). Spectrophotometric determination of tilidine using bromocresol green and bromophenol blue. in Acta Pharmaceutica Hungarica, 60(5-6), 179-181.
https://hdl.handle.net/21.15107/rcub_farfar_68

Živanov-Stakić D, Solomun L, Živanović L. Spectrophotometric determination of tilidine using bromocresol green and bromophenol blue. in Acta Pharmaceutica Hungarica. 1990;60(5-6):179-181.
https://hdl.handle.net/21.15107/rcub_farfar_68 .

Živanov-Stakić, Dobrila, Solomun, Ljiljana, Živanović, Ljiljana, "Spectrophotometric determination of tilidine using bromocresol green and bromophenol blue" in Acta Pharmaceutica Hungarica, 60, no. 5-6 (1990):179-181,
https://hdl.handle.net/21.15107/rcub_farfar_68 .

TY  - JOUR
AU  - Živanov-Stakić, Dobrila
AU  - Solomun, Ljiljana
AU  - Živanović, Ljiljana
PY  - 1989
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/50
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - High-performance liquid chromatographic method for the determination of bumetanide in pharmaceutical preparations
VL  - 7
IS  - 12
SP  - 1889
EP  - 1892
DO  - 10.1016/0731-7085(89)80209-2
ER  - 

@article{
author = "Živanov-Stakić, Dobrila and Solomun, Ljiljana and Živanović, Ljiljana",
year = "1989",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "High-performance liquid chromatographic method for the determination of bumetanide in pharmaceutical preparations",
volume = "7",
number = "12",
pages = "1889-1892",
doi = "10.1016/0731-7085(89)80209-2"
}

Živanov-Stakić, D., Solomun, L.,& Živanović, L.. (1989). High-performance liquid chromatographic method for the determination of bumetanide in pharmaceutical preparations. in Journal of Pharmaceutical and Biomedical Analysis, 7(12), 1889-1892.
https://doi.org/10.1016/0731-7085(89)80209-2

Živanov-Stakić D, Solomun L, Živanović L. High-performance liquid chromatographic method for the determination of bumetanide in pharmaceutical preparations. in Journal of Pharmaceutical and Biomedical Analysis. 1989;7(12):1889-1892.
doi:10.1016/0731-7085(89)80209-2 .

Živanov-Stakić, Dobrila, Solomun, Ljiljana, Živanović, Ljiljana, "High-performance liquid chromatographic method for the determination of bumetanide in pharmaceutical preparations" in Journal of Pharmaceutical and Biomedical Analysis, 7, no. 12 (1989):1889-1892,
https://doi.org/10.1016/0731-7085(89)80209-2 . .

TY  - JOUR
AU  - Živanov-Stakić, Dobrila
AU  - Solomun, Ljiljana
AU  - Živanović, Ljiljana
PY  - 1989
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/47
T2  - Farmaco
T1  - High-performance liquid chromatographic determination of tilidine in pharmaceutical dosage forms
VL  - 44
IS  - 7-8
SP  - 759
EP  - 762
UR  - https://hdl.handle.net/21.15107/rcub_farfar_47
ER  - 

@article{
author = "Živanov-Stakić, Dobrila and Solomun, Ljiljana and Živanović, Ljiljana",
year = "1989",
journal = "Farmaco",
title = "High-performance liquid chromatographic determination of tilidine in pharmaceutical dosage forms",
volume = "44",
number = "7-8",
pages = "759-762",
url = "https://hdl.handle.net/21.15107/rcub_farfar_47"
}

Živanov-Stakić, D., Solomun, L.,& Živanović, L.. (1989). High-performance liquid chromatographic determination of tilidine in pharmaceutical dosage forms. in Farmaco, 44(7-8), 759-762.
https://hdl.handle.net/21.15107/rcub_farfar_47

Živanov-Stakić D, Solomun L, Živanović L. High-performance liquid chromatographic determination of tilidine in pharmaceutical dosage forms. in Farmaco. 1989;44(7-8):759-762.
https://hdl.handle.net/21.15107/rcub_farfar_47 .

Živanov-Stakić, Dobrila, Solomun, Ljiljana, Živanović, Ljiljana, "High-performance liquid chromatographic determination of tilidine in pharmaceutical dosage forms" in Farmaco, 44, no. 7-8 (1989):759-762,
https://hdl.handle.net/21.15107/rcub_farfar_47 .