TY  - JOUR
AU  - Nikolić, Nenad D.
AU  - Medarević, Đorđe
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2492
AB  - This study investigates the use of high molecular weight polyethylene oxide (PEO WSR coagulant) for the preparation of sustained release matrix tablets containing high dose, highly water soluble drug, tramadol HCl. Proportion of PEO polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in tablet, tablet diameter and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Percentages of tramadol HCl released after 30 and 240 min were selected for evaluation of drug release, while tensile strength was used as indicator of tablet mechanical properties. Only proportion of tramadol HCl exhibits statistically significant effect on percentages of tramadol HCl released after 30 and 240 min, with higher, wherein increasing of the tramadol HCl proportion increased its release rate among the evaluated variables in selected ranges. All of the investigated factors exhibit statistically significant effect on tablets tensile strength, with the largest influence of filler type. Tablets prepared with highly compressible filler (microcrystalline cellulose) exhibit higher tensile strength and therefore better mechanical properties to those prepared with partially pregelatinized starch (starch 1500).
AB  - U radu je ispitivan uticaj formulacijskih i procesnih promenljivih na brzinu oslobađanja i mehaničke karakteristike matriks tableta izrađenih sa polietilen oksidom velike molekulske mase (PEO WSR koagulant), kao matriks formirajućim materijalom i visoko rastvoljivom lekovitom supstancom prisutnoj u velikoj dozi, tramadol hidrohloridom. Kao formulacijske promenljive varirane su: udeo polietilen oksidnog polimera (25 ili 35%), vrsta nerastvornog sredstva za dopunjavanje (mikrokristalna celuloza i parcijalno pregelirani skrob), udeo tramadol hidrohlorida (27,8 i 55,6%), količina leka u tableti (100 ili 200 mg). Pritisak kompresije je variran kao procesna promenljiva. Procenat tramadol hidrohlorida rastvoren nakon 30 i 240 min ispitivanja je izabran kao zavisno promenljiva za ispitivanje oslobađanja lekovite supstance, dok je zatezna čvrstoća izabrana kao zavisno promenljiva koja je indikator mehaničkih karakteristika tableta. Izvedena su dva seta eksperimenata, koji odgovaraju 25-2, odnosno 23 eksperimentalnom dizajnu. Tablete su izrađene na simulatoru kompakcije Prester. Simuliran je rad rotacione tablet prese Korch PH336, sa brzinom rotacije 30 rpm, što odgovara kapacitetu od 65000 tableta na sat. Ispitivanje uticaja faktora formulacije i procesa na oslobađanje tramadol hidrohlorida pokazalo je da se iz svih formulacija tramadol hidrohlorid oslobađa usporeno, linearnom kinetikom. Najveći uticaj na procenat oslobođenog leka imao je udeo leka u tableti. Sa povećanjem udela leka u tableti, povećavao se i procenat oslobođenog leka u navedenim vremenskih intervalima. Ostali isptivani faktori nisu imali značajan uticaj na brzinu oslobađanja. Ispitivanje mehaničkih karakteristika tableta pokazalo je da na zateznu čvrstoću izrađenih tableta najveći uticaj ima vrsta sredstva za dopunjavanje. Najveće vrednosti zatezne čvrstoće su dobijene u slučaju kada je mikrokristalna celuloza korišćena kao sredstvo za dopunjavanje, kao i kada je procenat polimera u tableti bio na višem nivou. Analiza dobijenih rezultata omogućava pravilan izbor vrste i koncentracije pomoćnih materija u formulaciji matriks tableta sa produženim oslobađanjem izrađenih sa polietilen oksidnim polimerom i visoko rastvorljivom lekovitom supstancom prisutnoj u velikoj dozi.
PB  - Savez hemijskih inženjera, Beograd
T2  - Hemijska industrija
T1  - Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets
T1  - Ispitivanje uticaja faktora formulacije i procesa na oslobađanje tramadol hidrohlorida i mehaničke karakteristike matriks tableta sa produženim oslobađanjem
VL  - 69
IS  - 5
SP  - 503
EP  - 510
DO  - 10.2298/HEMIND140317069N
ER  - 

@article{
author = "Nikolić, Nenad D. and Medarević, Đorđe and Ibrić, Svetlana and Đurić, Zorica",
year = "2015",
abstract = "This study investigates the use of high molecular weight polyethylene oxide (PEO WSR coagulant) for the preparation of sustained release matrix tablets containing high dose, highly water soluble drug, tramadol HCl. Proportion of PEO polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in tablet, tablet diameter and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Percentages of tramadol HCl released after 30 and 240 min were selected for evaluation of drug release, while tensile strength was used as indicator of tablet mechanical properties. Only proportion of tramadol HCl exhibits statistically significant effect on percentages of tramadol HCl released after 30 and 240 min, with higher, wherein increasing of the tramadol HCl proportion increased its release rate among the evaluated variables in selected ranges. All of the investigated factors exhibit statistically significant effect on tablets tensile strength, with the largest influence of filler type. Tablets prepared with highly compressible filler (microcrystalline cellulose) exhibit higher tensile strength and therefore better mechanical properties to those prepared with partially pregelatinized starch (starch 1500)., U radu je ispitivan uticaj formulacijskih i procesnih promenljivih na brzinu oslobađanja i mehaničke karakteristike matriks tableta izrađenih sa polietilen oksidom velike molekulske mase (PEO WSR koagulant), kao matriks formirajućim materijalom i visoko rastvoljivom lekovitom supstancom prisutnoj u velikoj dozi, tramadol hidrohloridom. Kao formulacijske promenljive varirane su: udeo polietilen oksidnog polimera (25 ili 35%), vrsta nerastvornog sredstva za dopunjavanje (mikrokristalna celuloza i parcijalno pregelirani skrob), udeo tramadol hidrohlorida (27,8 i 55,6%), količina leka u tableti (100 ili 200 mg). Pritisak kompresije je variran kao procesna promenljiva. Procenat tramadol hidrohlorida rastvoren nakon 30 i 240 min ispitivanja je izabran kao zavisno promenljiva za ispitivanje oslobađanja lekovite supstance, dok je zatezna čvrstoća izabrana kao zavisno promenljiva koja je indikator mehaničkih karakteristika tableta. Izvedena su dva seta eksperimenata, koji odgovaraju 25-2, odnosno 23 eksperimentalnom dizajnu. Tablete su izrađene na simulatoru kompakcije Prester. Simuliran je rad rotacione tablet prese Korch PH336, sa brzinom rotacije 30 rpm, što odgovara kapacitetu od 65000 tableta na sat. Ispitivanje uticaja faktora formulacije i procesa na oslobađanje tramadol hidrohlorida pokazalo je da se iz svih formulacija tramadol hidrohlorid oslobađa usporeno, linearnom kinetikom. Najveći uticaj na procenat oslobođenog leka imao je udeo leka u tableti. Sa povećanjem udela leka u tableti, povećavao se i procenat oslobođenog leka u navedenim vremenskih intervalima. Ostali isptivani faktori nisu imali značajan uticaj na brzinu oslobađanja. Ispitivanje mehaničkih karakteristika tableta pokazalo je da na zateznu čvrstoću izrađenih tableta najveći uticaj ima vrsta sredstva za dopunjavanje. Najveće vrednosti zatezne čvrstoće su dobijene u slučaju kada je mikrokristalna celuloza korišćena kao sredstvo za dopunjavanje, kao i kada je procenat polimera u tableti bio na višem nivou. Analiza dobijenih rezultata omogućava pravilan izbor vrste i koncentracije pomoćnih materija u formulaciji matriks tableta sa produženim oslobađanjem izrađenih sa polietilen oksidnim polimerom i visoko rastvorljivom lekovitom supstancom prisutnoj u velikoj dozi.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "Hemijska industrija",
title = "Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets, Ispitivanje uticaja faktora formulacije i procesa na oslobađanje tramadol hidrohlorida i mehaničke karakteristike matriks tableta sa produženim oslobađanjem",
volume = "69",
number = "5",
pages = "503-510",
doi = "10.2298/HEMIND140317069N"
}

Nikolić, N. D., Medarević, Đ., Ibrić, S.,& Đurić, Z.. (2015). Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets. in Hemijska industrija
Savez hemijskih inženjera, Beograd., 69(5), 503-510.
https://doi.org/10.2298/HEMIND140317069N

Nikolić ND, Medarević Đ, Ibrić S, Đurić Z. Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets. in Hemijska industrija. 2015;69(5):503-510.
doi:10.2298/HEMIND140317069N .

Nikolić, Nenad D., Medarević, Đorđe, Ibrić, Svetlana, Đurić, Zorica, "Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets" in Hemijska industrija, 69, no. 5 (2015):503-510,
https://doi.org/10.2298/HEMIND140317069N . .

TY  - JOUR
AU  - Nikolić, Nenad D.
AU  - Medarević, Đorđe
AU  - Đuriš, Jelena
AU  - Vasiljević, Dragana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2352
AB  - This study investigates the use of high molecular weight hydrophilic polymers, hypromellose and hydroxypropylcellulose, for the preparation of sustained release matrix tablets containing a high-dose highly soluble drug, tramadol HCl. The proportion of polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in the tablet and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Tensile strength was used as an indicator of the mechanical properties of the tablets. Experiments were performed with utilization of a compaction simulator, a device that simulates compaction profiles of large scale rotary tablet presses. In formulations with both polymers, the proportion of tramadol HCl was the most critical formulation parameter, wherein increasing the proportion of tramadol HCl increased its release rate in the early stages of drug release. Regarding the tablet mechanical characteristics, the filler type had the most pronounced effect in formulations with both polymers. Higher tensile strengths were obtained with Avicel PH 102 as the filler in formulations with both HPMC and HPC.
AB  - U ovom radu ispitivana je mogućnost primene hipromeloze i hidroksipropilceluloze, kao hidrofilnih polimera velike molekulske mase, za izradu matriks tableta sa produženim oslobađanjem, sa visoko rastvorljivom, visoko doziranom lekovitom supstancom tramadol-hidrohloridom. Udeo hidrofilnog polimera, vrsta nerastvorljivog sredstva za dopunjavanje, udeo tramadol-hidrohlorida, količina lekovite supstance u pojedinačnoj tableti i pritisak kompresije su prepoznati kao kritični parametri formulacije i procesa i u radu je ispitivan njihov uticaj na oslobađanje lekovite supstance i mehaničke karakteristike izrađenih tableta. Zatezna čvrstina tableta je korišćena kao indikator mehaničkih karakteristika tableta. Svi eksperimenti su vršeni korišćenjem simulatora kompakcije, koji omogućava simuliranje profila kompakcije rotacionih tablet mašina velikog kapaciteta. Kod formulacija izrađenih sa obe vrste polimera, udeo tramadol-hidrohlorida se pokazao kao najkritičniji faktor formulacije, pri čemu je povećanje udela tramadol-hidrohlorida dovelo do povećanja brzine oslobađanja ove lekovite supstance u početnim fazama oslobađanja lekovite supstance. Vrsta sredstva za dopunjavanje je pokazala najveći uticaj na mehaničke karakteristike izrađenih tableta, kod formulacija izrađenih sa oba tipa hidrofilnih polimera. Više vrednosti zatezne čvrstine tableta su postignute kod formulacija izrađenih korišćenjem Avicel PH 102 kao sredstva za dopunjavanje, bez obzira da li je u sastav tableta kao matriks polimer ulazila hipromeloza ili hidroksipropilceluloza.
PB  - Savez hemijskih inženjera, Beograd
T2  - CICEQ - Chemical Industry and Chemical Engineering Quarterly
T1  - Comparison of drug release and mechanical properties of tramadol hydrochloride matrix tablets prepared with selected hydrophilic polymers
T1  - Poređenje oslobađanja tramadol-hidrohlorida i mehaničkih karakteristika matriks tableta izrađenih sa odabranim hidrofilnim polimerima
VL  - 21
IS  - 3
SP  - 369
EP  - 378
DO  - 10.2298/CICEQ140613040N
ER  - 

@article{
author = "Nikolić, Nenad D. and Medarević, Đorđe and Đuriš, Jelena and Vasiljević, Dragana",
year = "2015",
abstract = "This study investigates the use of high molecular weight hydrophilic polymers, hypromellose and hydroxypropylcellulose, for the preparation of sustained release matrix tablets containing a high-dose highly soluble drug, tramadol HCl. The proportion of polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in the tablet and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Tensile strength was used as an indicator of the mechanical properties of the tablets. Experiments were performed with utilization of a compaction simulator, a device that simulates compaction profiles of large scale rotary tablet presses. In formulations with both polymers, the proportion of tramadol HCl was the most critical formulation parameter, wherein increasing the proportion of tramadol HCl increased its release rate in the early stages of drug release. Regarding the tablet mechanical characteristics, the filler type had the most pronounced effect in formulations with both polymers. Higher tensile strengths were obtained with Avicel PH 102 as the filler in formulations with both HPMC and HPC., U ovom radu ispitivana je mogućnost primene hipromeloze i hidroksipropilceluloze, kao hidrofilnih polimera velike molekulske mase, za izradu matriks tableta sa produženim oslobađanjem, sa visoko rastvorljivom, visoko doziranom lekovitom supstancom tramadol-hidrohloridom. Udeo hidrofilnog polimera, vrsta nerastvorljivog sredstva za dopunjavanje, udeo tramadol-hidrohlorida, količina lekovite supstance u pojedinačnoj tableti i pritisak kompresije su prepoznati kao kritični parametri formulacije i procesa i u radu je ispitivan njihov uticaj na oslobađanje lekovite supstance i mehaničke karakteristike izrađenih tableta. Zatezna čvrstina tableta je korišćena kao indikator mehaničkih karakteristika tableta. Svi eksperimenti su vršeni korišćenjem simulatora kompakcije, koji omogućava simuliranje profila kompakcije rotacionih tablet mašina velikog kapaciteta. Kod formulacija izrađenih sa obe vrste polimera, udeo tramadol-hidrohlorida se pokazao kao najkritičniji faktor formulacije, pri čemu je povećanje udela tramadol-hidrohlorida dovelo do povećanja brzine oslobađanja ove lekovite supstance u početnim fazama oslobađanja lekovite supstance. Vrsta sredstva za dopunjavanje je pokazala najveći uticaj na mehaničke karakteristike izrađenih tableta, kod formulacija izrađenih sa oba tipa hidrofilnih polimera. Više vrednosti zatezne čvrstine tableta su postignute kod formulacija izrađenih korišćenjem Avicel PH 102 kao sredstva za dopunjavanje, bez obzira da li je u sastav tableta kao matriks polimer ulazila hipromeloza ili hidroksipropilceluloza.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "CICEQ - Chemical Industry and Chemical Engineering Quarterly",
title = "Comparison of drug release and mechanical properties of tramadol hydrochloride matrix tablets prepared with selected hydrophilic polymers, Poređenje oslobađanja tramadol-hidrohlorida i mehaničkih karakteristika matriks tableta izrađenih sa odabranim hidrofilnim polimerima",
volume = "21",
number = "3",
pages = "369-378",
doi = "10.2298/CICEQ140613040N"
}

Nikolić, N. D., Medarević, Đ., Đuriš, J.,& Vasiljević, D.. (2015). Comparison of drug release and mechanical properties of tramadol hydrochloride matrix tablets prepared with selected hydrophilic polymers. in CICEQ - Chemical Industry and Chemical Engineering Quarterly
Savez hemijskih inženjera, Beograd., 21(3), 369-378.
https://doi.org/10.2298/CICEQ140613040N

Nikolić ND, Medarević Đ, Đuriš J, Vasiljević D. Comparison of drug release and mechanical properties of tramadol hydrochloride matrix tablets prepared with selected hydrophilic polymers. in CICEQ - Chemical Industry and Chemical Engineering Quarterly. 2015;21(3):369-378.
doi:10.2298/CICEQ140613040N .

Nikolić, Nenad D., Medarević, Đorđe, Đuriš, Jelena, Vasiljević, Dragana, "Comparison of drug release and mechanical properties of tramadol hydrochloride matrix tablets prepared with selected hydrophilic polymers" in CICEQ - Chemical Industry and Chemical Engineering Quarterly, 21, no. 3 (2015):369-378,
https://doi.org/10.2298/CICEQ140613040N . .

TY  - JOUR
AU  - Nikolić, Nenad D.
AU  - Ibrić, Svetlana
AU  - Medarević, Đorđe
AU  - Đurić, Zorica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2136
AB  - The aim of this study was establishing design space for robust formulation of hydrophilic extended release matrix tablets with tramadol hydrochloride as highly soluble, high dose drug. In the first part of the study, linear relationship between slope of Higuchi's model (K-h) and tablet surface/tablet volume (SA/V) ratio was confirmed varying drug loading in the range between 27.78 and 55.56% (w/w). Established relationship was tested in the second part of the study using different tablet shapes and sizes. Compression force was varied between 160 MPa and 300 MPa as critical process parameter, while drug loading and polymer concentration were recognized as critical input material attributes. High correlation was established between experimentally observed drug release profiles and drug release profiles predicted using K-h-SA/V relationship. Design space was established, where drug release could be accurately predicted for any drug loading/polymer content/compression force in the investigated range.
PB  - Colegio Farmaceuticos Provincia De Buenos Aires, La Plata
T2  - Latin American Journal of Pharmacy
T1  - Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets
VL  - 33
IS  - 7
SP  - 1131
EP  - 1138
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2136
ER  - 

@article{
author = "Nikolić, Nenad D. and Ibrić, Svetlana and Medarević, Đorđe and Đurić, Zorica",
year = "2014",
abstract = "The aim of this study was establishing design space for robust formulation of hydrophilic extended release matrix tablets with tramadol hydrochloride as highly soluble, high dose drug. In the first part of the study, linear relationship between slope of Higuchi's model (K-h) and tablet surface/tablet volume (SA/V) ratio was confirmed varying drug loading in the range between 27.78 and 55.56% (w/w). Established relationship was tested in the second part of the study using different tablet shapes and sizes. Compression force was varied between 160 MPa and 300 MPa as critical process parameter, while drug loading and polymer concentration were recognized as critical input material attributes. High correlation was established between experimentally observed drug release profiles and drug release profiles predicted using K-h-SA/V relationship. Design space was established, where drug release could be accurately predicted for any drug loading/polymer content/compression force in the investigated range.",
publisher = "Colegio Farmaceuticos Provincia De Buenos Aires, La Plata",
journal = "Latin American Journal of Pharmacy",
title = "Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets",
volume = "33",
number = "7",
pages = "1131-1138",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2136"
}

Nikolić, N. D., Ibrić, S., Medarević, Đ.,& Đurić, Z.. (2014). Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets. in Latin American Journal of Pharmacy
Colegio Farmaceuticos Provincia De Buenos Aires, La Plata., 33(7), 1131-1138.
https://hdl.handle.net/21.15107/rcub_farfar_2136

Nikolić ND, Ibrić S, Medarević Đ, Đurić Z. Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets. in Latin American Journal of Pharmacy. 2014;33(7):1131-1138.
https://hdl.handle.net/21.15107/rcub_farfar_2136 .

Nikolić, Nenad D., Ibrić, Svetlana, Medarević, Đorđe, Đurić, Zorica, "Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets" in Latin American Journal of Pharmacy, 33, no. 7 (2014):1131-1138,
https://hdl.handle.net/21.15107/rcub_farfar_2136 .

TY  - CONF
AU  - Nikolić, Nenad D.
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/794
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju
T1  - Kvalifikacija performansi pilot linije za granulaciju - uticaj veličine šarže na specifikaciju proizvoda
VL  - 56
IS  - 4
SP  - 456
EP  - 456
UR  - https://hdl.handle.net/21.15107/rcub_farfar_794
ER  - 

@conference{
author = "Nikolić, Nenad D. and Đurić, Zorica and Ibrić, Svetlana",
year = "2006",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Kvalifikacija performansi pilot linije za granulaciju - uticaj veličine šarže na specifikaciju proizvoda",
volume = "56",
number = "4",
pages = "456-456",
url = "https://hdl.handle.net/21.15107/rcub_farfar_794"
}

Nikolić, N. D., Đurić, Z.,& Ibrić, S.. (2006). Kvalifikacija performansi pilot linije za granulaciju - uticaj veličine šarže na specifikaciju proizvoda. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 56(4), 456-456.
https://hdl.handle.net/21.15107/rcub_farfar_794

Nikolić ND, Đurić Z, Ibrić S. Kvalifikacija performansi pilot linije za granulaciju - uticaj veličine šarže na specifikaciju proizvoda. in Arhiv za farmaciju. 2006;56(4):456-456.
https://hdl.handle.net/21.15107/rcub_farfar_794 .

Nikolić, Nenad D., Đurić, Zorica, Ibrić, Svetlana, "Kvalifikacija performansi pilot linije za granulaciju - uticaj veličine šarže na specifikaciju proizvoda" in Arhiv za farmaciju, 56, no. 4 (2006):456-456,
https://hdl.handle.net/21.15107/rcub_farfar_794 .