TY  - JOUR
AU  - Medarević, Đorđe
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
AU  - Mitrić, Miodrag
AU  - Kachrimanis, Kyriakos
PY  - 2018
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7655
AB  - The aim of this study is to develop nanosuspension of carvedilol (CRV) by wet media milling. Concentration of polymeric stabilizer (hydroxypropyl cellulose-HPC-SL), milling speed and size of milling beads were identified as critical formulation and process parameters and their effect on CRV particle size after 60 min of milling was assessed using a Box-Behnken experimental design. Optimized nanosuspension was solidified using spray drying and freeze drying and subjected to solid state characterization. Low stabilizer concentration (10%), low milling speed (300 rpm) with small milling beads (0.1 mm) were found as optimal milling conditions. Crystal lattice simulation identified potential slip plane within CRV crystals, where fractures are the most likely to occur. Calculated mechanical properties of CRV crystal indicates that low energy stress is sufficient to initiate fracture, if applied in the correct direction, explaining the advantage of using smaller milling beads. Only spray dried nanosuspension redispersed to original nanoparticles, while particle agglomeration during freeze drying prevented sample redispersion. Wet milling and spray drying did not induce polymorphic transition of CRV, while there is indication of polymorphic transition during freeze drying, making spray drying as the preferred solidification method.
T2  - International Journal of Pharmaceutics
T1  - Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling
VL  - 540
IS  - 1-2
SP  - 150
EP  - 161
DO  - 10.1016/j.ijpharm.2018.02.011
ER  - 

@article{
author = "Medarević, Đorđe and Đuriš, Jelena and Ibrić, Svetlana and Mitrić, Miodrag and Kachrimanis, Kyriakos",
year = "2018",
abstract = "The aim of this study is to develop nanosuspension of carvedilol (CRV) by wet media milling. Concentration of polymeric stabilizer (hydroxypropyl cellulose-HPC-SL), milling speed and size of milling beads were identified as critical formulation and process parameters and their effect on CRV particle size after 60 min of milling was assessed using a Box-Behnken experimental design. Optimized nanosuspension was solidified using spray drying and freeze drying and subjected to solid state characterization. Low stabilizer concentration (10%), low milling speed (300 rpm) with small milling beads (0.1 mm) were found as optimal milling conditions. Crystal lattice simulation identified potential slip plane within CRV crystals, where fractures are the most likely to occur. Calculated mechanical properties of CRV crystal indicates that low energy stress is sufficient to initiate fracture, if applied in the correct direction, explaining the advantage of using smaller milling beads. Only spray dried nanosuspension redispersed to original nanoparticles, while particle agglomeration during freeze drying prevented sample redispersion. Wet milling and spray drying did not induce polymorphic transition of CRV, while there is indication of polymorphic transition during freeze drying, making spray drying as the preferred solidification method.",
journal = "International Journal of Pharmaceutics",
title = "Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling",
volume = "540",
number = "1-2",
pages = "150-161",
doi = "10.1016/j.ijpharm.2018.02.011"
}

Medarević, Đ., Đuriš, J., Ibrić, S., Mitrić, M.,& Kachrimanis, K.. (2018). Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling. in International Journal of Pharmaceutics, 540(1-2), 150-161.
https://doi.org/10.1016/j.ijpharm.2018.02.011

Medarević Đ, Đuriš J, Ibrić S, Mitrić M, Kachrimanis K. Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling. in International Journal of Pharmaceutics. 2018;540(1-2):150-161.
doi:10.1016/j.ijpharm.2018.02.011 .

Medarević, Đorđe, Đuriš, Jelena, Ibrić, Svetlana, Mitrić, Miodrag, Kachrimanis, Kyriakos, "Optimization of formulation and process parameters for the production of carvedilol nanosuspension by wet media milling" in International Journal of Pharmaceutics, 540, no. 1-2 (2018):150-161,
https://doi.org/10.1016/j.ijpharm.2018.02.011 . .

TY  - JOUR
AU  - Medarević, Đorđe 
AU  - Kachrimanis, Kyriakos
AU  - Mitrić, Miodrag
AU  - Đuriš, Jelena
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/915
AB  - This study investigates the potential of poloxamers as solid dispersions (SDs) carriers in improving the dissolution rate of a poorly soluble drug, carbamazepine (CBZ). Solid dispersions were prepared with poloxamer 188 (P188) and poloxamer 407 (P407) by melting method in different drug:carrier ratios (1:1, 1:2 and 1:3). Prepared samples were characterized using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (HSM), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) to investigate drug physical state within the SDs matrix, possible polymorphic transitions and drug-polymer interactions. The interactions between CBZ molecules and polymeric chains were also evaluated using molecular dynamics simulation (MDS) technique. The most thermodynamically stable polymorphic form III of CBZ was present in all SDs, regardless of the type of poloxamer and drug-to-carrier ratio. The absence of drug-polymer interactions was observed by FT-IR analysis and additionally confirmed by MDS. Formation of persistent hydrogen bond between two CBZ molecules, observed by MDS indicate high tendency of CBZ molecules to aggregate and form crystalline phase within dispersion. P188 exhibit higher efficiency in increasing CBZ dissolution rate due to its more pronounced hydrophilic properties, while increasing poloxamers concentration resulted in decreasing drug release rate, as a consequence of their thermoreversible gelation.
T2  - Pharmaceutical Development and Technology
T1  - Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions
VL  - 21
IS  - 3
SP  - 268
EP  - 276
DO  - 10.3109/10837450.2014.996899
ER  - 

@article{
author = "Medarević, Đorđe  and Kachrimanis, Kyriakos and Mitrić, Miodrag and Đuriš, Jelena and Đurić, Zorica and Ibrić, Svetlana",
year = "2016",
abstract = "This study investigates the potential of poloxamers as solid dispersions (SDs) carriers in improving the dissolution rate of a poorly soluble drug, carbamazepine (CBZ). Solid dispersions were prepared with poloxamer 188 (P188) and poloxamer 407 (P407) by melting method in different drug:carrier ratios (1:1, 1:2 and 1:3). Prepared samples were characterized using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (HSM), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) to investigate drug physical state within the SDs matrix, possible polymorphic transitions and drug-polymer interactions. The interactions between CBZ molecules and polymeric chains were also evaluated using molecular dynamics simulation (MDS) technique. The most thermodynamically stable polymorphic form III of CBZ was present in all SDs, regardless of the type of poloxamer and drug-to-carrier ratio. The absence of drug-polymer interactions was observed by FT-IR analysis and additionally confirmed by MDS. Formation of persistent hydrogen bond between two CBZ molecules, observed by MDS indicate high tendency of CBZ molecules to aggregate and form crystalline phase within dispersion. P188 exhibit higher efficiency in increasing CBZ dissolution rate due to its more pronounced hydrophilic properties, while increasing poloxamers concentration resulted in decreasing drug release rate, as a consequence of their thermoreversible gelation.",
journal = "Pharmaceutical Development and Technology",
title = "Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions",
volume = "21",
number = "3",
pages = "268-276",
doi = "10.3109/10837450.2014.996899"
}

Medarević, Đ., Kachrimanis, K., Mitrić, M., Đuriš, J., Đurić, Z.,& Ibrić, S.. (2016). Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions. in Pharmaceutical Development and Technology, 21(3), 268-276.
https://doi.org/10.3109/10837450.2014.996899

Medarević Đ, Kachrimanis K, Mitrić M, Đuriš J, Đurić Z, Ibrić S. Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions. in Pharmaceutical Development and Technology. 2016;21(3):268-276.
doi:10.3109/10837450.2014.996899 .

Medarević, Đorđe , Kachrimanis, Kyriakos, Mitrić, Miodrag, Đuriš, Jelena, Đurić, Zorica, Ibrić, Svetlana, "Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions" in Pharmaceutical Development and Technology, 21, no. 3 (2016):268-276,
https://doi.org/10.3109/10837450.2014.996899 . .