TY  - JOUR
AU  - Vujić, Zorica
AU  - Mulavdić, Nedzad
AU  - Smajić, Miralem
AU  - Brborić, Jasmina
AU  - Stanković, Predrag
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1703
AB  - Experimental design method was used for HPLC determination of irbesartan and hydrochlorothiazide in combined dosage forms. The traditional approach for optimization of experiments is time-consuming, involves a large number of runs and does not allow establishing the multiple interacting parameters. The main advantages of the experimental design method include the simultaneous screening of a larger number of factors affecting response and the estimation of possible interactions. On the basis of preliminary experiments, three factors-independent variables were selected as inputs (methanol content, pH of the mobile phase and temperature) and as dependent variables, five responses (resolution, symmetry of irbesartan peak, symmetry of hydrochlorothiazide peak, retention factor of irbesartan and retention factor of hydrochlorothiazide) were chosen. A full 2(3) factorial design, where factors were examined at two different levels ("low" and "high") was used to determine which factors had an effect on the studied response. Afterwards, experimental design was used to optimize these influent parameters in the previously selected experimental domain. The novelty of our method lies in the optimization step accomplished by Derringer's desirability function. After optimizing the experimental conditions a separation was conducted on a Supelcosil C-18 (150 mm x 4.6 mm, 5 mu m particle size) column with a mobile phase consisting of methanol-tetrahydrofuran-acetate buffer 47:10:43 v/v/v, pH 6.5 and a column temperature of 25 degrees C. The developed method was successfully applied to the simultaneous separation of these drug-active compounds in their commercial pharmaceutical dosage forms.
PB  - MDPI, Basel
T2  - Molecules
T1  - Simultaneous Analysis of Irbesartan and Hydrochlorothiazide: An Improved HPLC Method with the Aid of a Chemometric Protocol
VL  - 17
IS  - 3
SP  - 3461
EP  - 3474
DO  - 10.3390/molecules17033461
ER  - 

@article{
author = "Vujić, Zorica and Mulavdić, Nedzad and Smajić, Miralem and Brborić, Jasmina and Stanković, Predrag",
year = "2012",
abstract = "Experimental design method was used for HPLC determination of irbesartan and hydrochlorothiazide in combined dosage forms. The traditional approach for optimization of experiments is time-consuming, involves a large number of runs and does not allow establishing the multiple interacting parameters. The main advantages of the experimental design method include the simultaneous screening of a larger number of factors affecting response and the estimation of possible interactions. On the basis of preliminary experiments, three factors-independent variables were selected as inputs (methanol content, pH of the mobile phase and temperature) and as dependent variables, five responses (resolution, symmetry of irbesartan peak, symmetry of hydrochlorothiazide peak, retention factor of irbesartan and retention factor of hydrochlorothiazide) were chosen. A full 2(3) factorial design, where factors were examined at two different levels ("low" and "high") was used to determine which factors had an effect on the studied response. Afterwards, experimental design was used to optimize these influent parameters in the previously selected experimental domain. The novelty of our method lies in the optimization step accomplished by Derringer's desirability function. After optimizing the experimental conditions a separation was conducted on a Supelcosil C-18 (150 mm x 4.6 mm, 5 mu m particle size) column with a mobile phase consisting of methanol-tetrahydrofuran-acetate buffer 47:10:43 v/v/v, pH 6.5 and a column temperature of 25 degrees C. The developed method was successfully applied to the simultaneous separation of these drug-active compounds in their commercial pharmaceutical dosage forms.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Simultaneous Analysis of Irbesartan and Hydrochlorothiazide: An Improved HPLC Method with the Aid of a Chemometric Protocol",
volume = "17",
number = "3",
pages = "3461-3474",
doi = "10.3390/molecules17033461"
}

Vujić, Z., Mulavdić, N., Smajić, M., Brborić, J.,& Stanković, P.. (2012). Simultaneous Analysis of Irbesartan and Hydrochlorothiazide: An Improved HPLC Method with the Aid of a Chemometric Protocol. in Molecules
MDPI, Basel., 17(3), 3461-3474.
https://doi.org/10.3390/molecules17033461

Vujić Z, Mulavdić N, Smajić M, Brborić J, Stanković P. Simultaneous Analysis of Irbesartan and Hydrochlorothiazide: An Improved HPLC Method with the Aid of a Chemometric Protocol. in Molecules. 2012;17(3):3461-3474.
doi:10.3390/molecules17033461 .

Vujić, Zorica, Mulavdić, Nedzad, Smajić, Miralem, Brborić, Jasmina, Stanković, Predrag, "Simultaneous Analysis of Irbesartan and Hydrochlorothiazide: An Improved HPLC Method with the Aid of a Chemometric Protocol" in Molecules, 17, no. 3 (2012):3461-3474,
https://doi.org/10.3390/molecules17033461 . .

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 . .