TY  - JOUR
AU  - Pešić, Nikola
AU  - Dapčević, Aleksandra
AU  - Ivković, Branka
AU  - Kachrimanis, Kyriakos
AU  - Mitrić, Miodrag
AU  - Ibrić, Svetlana
AU  - Medarević, Đorđe
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3964
AB  - In this study, four low molecular weight (LMW) excipients, tryptophan (TRY), phenylalanine (PHE), lysine (LYS) and saccharin (SAC) were evaluated as co-formers to generate co-amorphous systems (CAMS) by ball milling with carvedilol (CRV). Mixtures of CRV and LMW excipient in 1:0.5, 1:1 and 1:2 drug:excipient molar ratios were ball milled and analysed by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform (FT-IR) infrared spectroscopy and dissolution testing. CAMS were formed by milling of a mixture of CRV with TRY in 1:2 M ratio and SAC in 1:1 M ratio, while amorphization of only CRV was achieved in other mixtures with SAC. In other samples containing TRY and PHE, milling resulted in partial amorphization, while LYS was the least suitable excipient for the amorphization of CRV. Unexpectedly, the highest supersaturation of CRV was achieved from samples containing CRV and LYS in 1:1 and 1:2 M ratios, despite the absence of a significant reduction in CRV crystallinity upon milling of these samples. Increase of hydrophobic surface area caused by milling of samples with TRY and PHE and agglomeration during dissolution testing of samples containing SAC are likely causes of poor dissolution performance of mixtures containing fully or partially amorphous CRV.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol
VL  - 608
DO  - 10.1016/j.ijpharm.2021.121033
ER  - 

@article{
author = "Pešić, Nikola and Dapčević, Aleksandra and Ivković, Branka and Kachrimanis, Kyriakos and Mitrić, Miodrag and Ibrić, Svetlana and Medarević, Đorđe",
year = "2021",
abstract = "In this study, four low molecular weight (LMW) excipients, tryptophan (TRY), phenylalanine (PHE), lysine (LYS) and saccharin (SAC) were evaluated as co-formers to generate co-amorphous systems (CAMS) by ball milling with carvedilol (CRV). Mixtures of CRV and LMW excipient in 1:0.5, 1:1 and 1:2 drug:excipient molar ratios were ball milled and analysed by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform (FT-IR) infrared spectroscopy and dissolution testing. CAMS were formed by milling of a mixture of CRV with TRY in 1:2 M ratio and SAC in 1:1 M ratio, while amorphization of only CRV was achieved in other mixtures with SAC. In other samples containing TRY and PHE, milling resulted in partial amorphization, while LYS was the least suitable excipient for the amorphization of CRV. Unexpectedly, the highest supersaturation of CRV was achieved from samples containing CRV and LYS in 1:1 and 1:2 M ratios, despite the absence of a significant reduction in CRV crystallinity upon milling of these samples. Increase of hydrophobic surface area caused by milling of samples with TRY and PHE and agglomeration during dissolution testing of samples containing SAC are likely causes of poor dissolution performance of mixtures containing fully or partially amorphous CRV.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol",
volume = "608",
doi = "10.1016/j.ijpharm.2021.121033"
}

Pešić, N., Dapčević, A., Ivković, B., Kachrimanis, K., Mitrić, M., Ibrić, S.,& Medarević, Đ.. (2021). Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol. in International Journal of Pharmaceutics
Elsevier B.V.., 608.
https://doi.org/10.1016/j.ijpharm.2021.121033

Pešić N, Dapčević A, Ivković B, Kachrimanis K, Mitrić M, Ibrić S, Medarević Đ. Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol. in International Journal of Pharmaceutics. 2021;608.
doi:10.1016/j.ijpharm.2021.121033 .

Pešić, Nikola, Dapčević, Aleksandra, Ivković, Branka, Kachrimanis, Kyriakos, Mitrić, Miodrag, Ibrić, Svetlana, Medarević, Đorđe, "Potential application of low molecular weight excipients for amorphization and dissolution enhancement of carvedilol" in International Journal of Pharmaceutics, 608 (2021),
https://doi.org/10.1016/j.ijpharm.2021.121033 . .

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Ibrić, Svetlana
AU  - Vardaka, Elisavet
AU  - Mitrić, Miodrag
AU  - Nikolakakis, Ioannis
AU  - Kachrimanis, Kyriakos
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3497
AB  - Nanocrystal formation for the dissolution enhancement of glimepiride was attempted
by wet media milling. Di erent stabilizers were tested and the obtained nanosuspensions were
solidified by spray drying in presence of mannitol, and characterized regarding their redispersibility
by dynamic light scattering, physicochemical properties by di erential scanning calorimetry (DSC),
FT-IR spectroscopy, powder X-ray di raction (PXRD), and scanning electron microcopy (SEM), as
well as dissolution rate. Lattice energy frameworks combined with topology analysis were used in
order to gain insight into the mechanisms of particle fracture. It was found that nanosuspensions with
narrow size distribution can be obtained in presence of poloxamer 188, HPC-SL and Pharmacoat® 603
stabilizers, with poloxamer giving poor redispersibility due to melting and sticking of nanocrystals
during spray drying. DSC and FT-IR studies showed that glimepiride does not undergo polymorphic
transformations during processing, and that the milling process induces changes in the hydrogen
bonding patterns of glimepiride crystals. Lattice energy framework and topology analysis revealed
the existence of a possible slip plane on the (101) surface, which was experimentally verified by PXRD
analysis. Dissolution testing proved the superior performance of nanocrystals, and emphasized the
important influence of the stabilizer on the dissolution rate of the nanocrystals.
PB  - MDPI
T2  - Pharmaceutics
T1  - Insight into the formation of glimepiride nanocrystals by wet media milling
VL  - 12
IS  - 1
DO  - 10.3390/pharmaceutics12010053
ER  - 

@article{
author = "Medarević, Đorđe and Ibrić, Svetlana and Vardaka, Elisavet and Mitrić, Miodrag and Nikolakakis, Ioannis and Kachrimanis, Kyriakos",
year = "2020",
abstract = "Nanocrystal formation for the dissolution enhancement of glimepiride was attempted
by wet media milling. Di erent stabilizers were tested and the obtained nanosuspensions were
solidified by spray drying in presence of mannitol, and characterized regarding their redispersibility
by dynamic light scattering, physicochemical properties by di erential scanning calorimetry (DSC),
FT-IR spectroscopy, powder X-ray di raction (PXRD), and scanning electron microcopy (SEM), as
well as dissolution rate. Lattice energy frameworks combined with topology analysis were used in
order to gain insight into the mechanisms of particle fracture. It was found that nanosuspensions with
narrow size distribution can be obtained in presence of poloxamer 188, HPC-SL and Pharmacoat® 603
stabilizers, with poloxamer giving poor redispersibility due to melting and sticking of nanocrystals
during spray drying. DSC and FT-IR studies showed that glimepiride does not undergo polymorphic
transformations during processing, and that the milling process induces changes in the hydrogen
bonding patterns of glimepiride crystals. Lattice energy framework and topology analysis revealed
the existence of a possible slip plane on the (101) surface, which was experimentally verified by PXRD
analysis. Dissolution testing proved the superior performance of nanocrystals, and emphasized the
important influence of the stabilizer on the dissolution rate of the nanocrystals.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Insight into the formation of glimepiride nanocrystals by wet media milling",
volume = "12",
number = "1",
doi = "10.3390/pharmaceutics12010053"
}

Medarević, Đ., Ibrić, S., Vardaka, E., Mitrić, M., Nikolakakis, I.,& Kachrimanis, K.. (2020). Insight into the formation of glimepiride nanocrystals by wet media milling. in Pharmaceutics
MDPI., 12(1).
https://doi.org/10.3390/pharmaceutics12010053

Medarević Đ, Ibrić S, Vardaka E, Mitrić M, Nikolakakis I, Kachrimanis K. Insight into the formation of glimepiride nanocrystals by wet media milling. in Pharmaceutics. 2020;12(1).
doi:10.3390/pharmaceutics12010053 .

Medarević, Đorđe, Ibrić, Svetlana, Vardaka, Elisavet, Mitrić, Miodrag, Nikolakakis, Ioannis, Kachrimanis, Kyriakos, "Insight into the formation of glimepiride nanocrystals by wet media milling" in Pharmaceutics, 12, no. 1 (2020),
https://doi.org/10.3390/pharmaceutics12010053 . .

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
AU  - Mitrić, Miodrag
AU  - Kachrimanis, Kyriakos
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3171
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.
PB  - Elsevier Science BV, Amsterdam
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.",
publisher = "Elsevier Science BV, Amsterdam",
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
Elsevier Science BV, Amsterdam., 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://farfar.pharmacy.bg.ac.rs/handle/123456789/2570
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.
PB  - Taylor & Francis Ltd, Abingdon
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.",
publisher = "Taylor & Francis Ltd, Abingdon",
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
Taylor & Francis Ltd, Abingdon., 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 . .

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Kachrimanis, Kyriakos
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2321
AB  - In this study binary carbamazepine-hydroxypropyl-beta-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus (R) and two types of hydroxypropyl methylcellulose-Metolose (R) 90SH-100 and Metolose (R) 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-B-cyclodextrin for carbamazepine. Evaluation of carbamaze pine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-beta-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-beta-cyclodextrin and ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-beta-cyclodextrin and ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-Soluplus (R) systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin
VL  - 78
SP  - 273
EP  - 285
DO  - 10.1016/j.ejps.2015.08.001
ER  - 

@article{
author = "Medarević, Đorđe and Kachrimanis, Kyriakos and Đurić, Zorica and Ibrić, Svetlana",
year = "2015",
abstract = "In this study binary carbamazepine-hydroxypropyl-beta-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus (R) and two types of hydroxypropyl methylcellulose-Metolose (R) 90SH-100 and Metolose (R) 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-B-cyclodextrin for carbamazepine. Evaluation of carbamaze pine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-beta-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-beta-cyclodextrin and ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-beta-cyclodextrin and ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-Soluplus (R) systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin",
volume = "78",
pages = "273-285",
doi = "10.1016/j.ejps.2015.08.001"
}

Medarević, Đ., Kachrimanis, K., Đurić, Z.,& Ibrić, S.. (2015). Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 78, 273-285.
https://doi.org/10.1016/j.ejps.2015.08.001

Medarević Đ, Kachrimanis K, Đurić Z, Ibrić S. Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin. in European Journal of Pharmaceutical Sciences. 2015;78:273-285.
doi:10.1016/j.ejps.2015.08.001 .

Medarević, Đorđe, Kachrimanis, Kyriakos, Đurić, Zorica, Ibrić, Svetlana, "Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin" in European Journal of Pharmaceutical Sciences, 78 (2015):273-285,
https://doi.org/10.1016/j.ejps.2015.08.001 . .

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  - Đuriš, Jelena
AU  - Ioannis, Nikolakakis
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
AU  - Kachrimanis, Kyriakos
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2185
AB  - ObjectivesThis study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. MethodsPrepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Key findingsSolid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ:Poloxamer 407=1:1 showing the highest increase in CBZ release rate. ConclusionsInteractions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate.
PB  - Wiley-Blackwell, Hoboken
T2  - Journal of Pharmacy and Pharmacology
T1  - Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design
VL  - 66
IS  - 2
SP  - 232
EP  - 243
DO  - 10.1111/jphp.12199
ER  - 

@article{
author = "Đuriš, Jelena and Ioannis, Nikolakakis and Ibrić, Svetlana and Đurić, Zorica and Kachrimanis, Kyriakos",
year = "2014",
abstract = "ObjectivesThis study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. MethodsPrepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Key findingsSolid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ:Poloxamer 407=1:1 showing the highest increase in CBZ release rate. ConclusionsInteractions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Pharmacy and Pharmacology",
title = "Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design",
volume = "66",
number = "2",
pages = "232-243",
doi = "10.1111/jphp.12199"
}

Đuriš, J., Ioannis, N., Ibrić, S., Đurić, Z.,& Kachrimanis, K.. (2014). Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design. in Journal of Pharmacy and Pharmacology
Wiley-Blackwell, Hoboken., 66(2), 232-243.
https://doi.org/10.1111/jphp.12199

Đuriš J, Ioannis N, Ibrić S, Đurić Z, Kachrimanis K. Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design. in Journal of Pharmacy and Pharmacology. 2014;66(2):232-243.
doi:10.1111/jphp.12199 .

Đuriš, Jelena, Ioannis, Nikolakakis, Ibrić, Svetlana, Đurić, Zorica, Kachrimanis, Kyriakos, "Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design" in Journal of Pharmacy and Pharmacology, 66, no. 2 (2014):232-243,
https://doi.org/10.1111/jphp.12199 . .

TY  - JOUR
AU  - Đuriš, Jelena
AU  - Nikolakakis, Ioannis
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
AU  - Kachrimanis, Kyriakos
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1997
AB  - Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic-polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus (R)) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential. scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus (R) was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. It was found that hot-melt extrusion of carbamazepine and Soluplus (R) is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed similar to 5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus (R) hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutics and Biopharmaceutics
T1  - Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting
VL  - 84
IS  - 1
SP  - 228
EP  - 237
DO  - 10.1016/j.ejpb.2012.12.018
ER  - 

@article{
author = "Đuriš, Jelena and Nikolakakis, Ioannis and Ibrić, Svetlana and Đurić, Zorica and Kachrimanis, Kyriakos",
year = "2013",
abstract = "Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic-polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus (R)) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential. scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus (R) was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. It was found that hot-melt extrusion of carbamazepine and Soluplus (R) is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed similar to 5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus (R) hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
title = "Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting",
volume = "84",
number = "1",
pages = "228-237",
doi = "10.1016/j.ejpb.2012.12.018"
}

Đuriš, J., Nikolakakis, I., Ibrić, S., Đurić, Z.,& Kachrimanis, K.. (2013). Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. in European Journal of Pharmaceutics and Biopharmaceutics
Elsevier Science BV, Amsterdam., 84(1), 228-237.
https://doi.org/10.1016/j.ejpb.2012.12.018

Đuriš J, Nikolakakis I, Ibrić S, Đurić Z, Kachrimanis K. Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. in European Journal of Pharmaceutics and Biopharmaceutics. 2013;84(1):228-237.
doi:10.1016/j.ejpb.2012.12.018 .

Đuriš, Jelena, Nikolakakis, Ioannis, Ibrić, Svetlana, Đurić, Zorica, Kachrimanis, Kyriakos, "Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting" in European Journal of Pharmaceutics and Biopharmaceutics, 84, no. 1 (2013):228-237,
https://doi.org/10.1016/j.ejpb.2012.12.018 . .

TY  - JOUR
AU  - Kolasinac, Nemanja
AU  - Kachrimanis, Kyriakos
AU  - Đuriš, Jelena
AU  - Homšek, Irena
AU  - Grujić, Branka
AU  - Ibrić, Svetlana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1989
AB  - Solid dispersion systems have been widely used to enhance dissolution rate and oral bioavailability of poorly water-soluble drugs. However, the formulation process development and scale-up present a number of difficulties which has greatly limited their commercial applications. In this study, solid dispersions (SDs) of desloratadine (DSL) with povidone (PVP) and crospovidone (cPVP) were prepared by spray coating technique. The process involved the spray application of 96% ethanol solution of DSL and PVP/cPVP, and subsequent deposition of the coprecipitates onto microcrystalline cellulose pellets during drying by air flow in a mini spray coater. The results from the present study demonstrated that the spray coating process is efficient in preparing SDs with enhanced drug dissolution rate and it is highly efficient in organic solvent removal. Both PVP and cPVP greatly improved drug dissolution rate by SDs, with PVP showing better solubilization capability. Very fast drug dissolution rate is achieved from SDs containing PVP regardless of differences in K grade. SD with smaller particles of cPVP have higher drug dissolution rate in comparison to the cPVP with larger particles. Results from physical state characterization indicate that DSL in SDs exist in the amorphous (high free-energy) state which is probably stabilized by PVP/cPVP. After 6-month accelerated stability study, DSL remains amorphous, while PVP and cPVP act as anti-plasticizing agents, offering efficient steric hindrance for nucleation and crystal growth.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Drug Development and Industrial Pharmacy
T1  - Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate
VL  - 39
IS  - 7
SP  - 1020
EP  - 1027
DO  - 10.3109/03639045.2012.694890
ER  - 

@article{
author = "Kolasinac, Nemanja and Kachrimanis, Kyriakos and Đuriš, Jelena and Homšek, Irena and Grujić, Branka and Ibrić, Svetlana",
year = "2013",
abstract = "Solid dispersion systems have been widely used to enhance dissolution rate and oral bioavailability of poorly water-soluble drugs. However, the formulation process development and scale-up present a number of difficulties which has greatly limited their commercial applications. In this study, solid dispersions (SDs) of desloratadine (DSL) with povidone (PVP) and crospovidone (cPVP) were prepared by spray coating technique. The process involved the spray application of 96% ethanol solution of DSL and PVP/cPVP, and subsequent deposition of the coprecipitates onto microcrystalline cellulose pellets during drying by air flow in a mini spray coater. The results from the present study demonstrated that the spray coating process is efficient in preparing SDs with enhanced drug dissolution rate and it is highly efficient in organic solvent removal. Both PVP and cPVP greatly improved drug dissolution rate by SDs, with PVP showing better solubilization capability. Very fast drug dissolution rate is achieved from SDs containing PVP regardless of differences in K grade. SD with smaller particles of cPVP have higher drug dissolution rate in comparison to the cPVP with larger particles. Results from physical state characterization indicate that DSL in SDs exist in the amorphous (high free-energy) state which is probably stabilized by PVP/cPVP. After 6-month accelerated stability study, DSL remains amorphous, while PVP and cPVP act as anti-plasticizing agents, offering efficient steric hindrance for nucleation and crystal growth.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Drug Development and Industrial Pharmacy",
title = "Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate",
volume = "39",
number = "7",
pages = "1020-1027",
doi = "10.3109/03639045.2012.694890"
}

Kolasinac, N., Kachrimanis, K., Đuriš, J., Homšek, I., Grujić, B.,& Ibrić, S.. (2013). Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate. in Drug Development and Industrial Pharmacy
Taylor & Francis Ltd, Abingdon., 39(7), 1020-1027.
https://doi.org/10.3109/03639045.2012.694890

Kolasinac N, Kachrimanis K, Đuriš J, Homšek I, Grujić B, Ibrić S. Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate. in Drug Development and Industrial Pharmacy. 2013;39(7):1020-1027.
doi:10.3109/03639045.2012.694890 .

Kolasinac, Nemanja, Kachrimanis, Kyriakos, Đuriš, Jelena, Homšek, Irena, Grujić, Branka, Ibrić, Svetlana, "Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate" in Drug Development and Industrial Pharmacy, 39, no. 7 (2013):1020-1027,
https://doi.org/10.3109/03639045.2012.694890 . .

TY  - JOUR
AU  - Mihajlović, Tijana
AU  - Kachrimanis, Kyriakos
AU  - Graovac, Adrijana
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1753
AB  - Due to the fact that the number of new poorly soluble active pharmaceutical ingredients is increasing, it is important to investigate the possibilities of improvement of their solubility in order to obtain a final pharmaceutical formulation with enhanced bioavailability. One of the strategies to increase drug solubility is the inclusion of the APIs in cyclodextrins. The aim of this study was to investigate the possibility of aripiprazole solubility improvement by inclusion in (2-hydroxy)propyl-beta-cyclodextrin (HPBCD) and simultaneous manipulation of pH of the medium and addition of polyvinylpyrrolidone. Aripiprazole-HPBCD complexes were prepared by spray drying aqueous drug-HPBCD solutions, and their properties were compared with those prepared by solvent-drop co-grinding and physical mixing. The obtained powders were characterized by thermoanalytical methods (TGA and DSC), FTIR spectroscopy, their dissolution properties were assessed, while the binding of aripiprazole into the cavity of HPBCD was studied by molecular docking simulations. The solubilization capacity was found to be dependent on pH as well as the buffer solution's ionic composition. The presence of PVP in the formulation could affect the solubilization capacity significantly, but further experimentation is required before its effect is fully understood. On the basis of solubility studies, the drug/HPBCD stoichiometry was found to be 1:3. The spray-dried products were free of crystalline aripiprazole, they possessed higher solubility and dissolution rate, and were stable enough over a prolonged period of storage. Spray drying of cyclodextrin solutions proved to be an appropriate and efficient technique for the preparation of highly soluble inclusion compounds of aripiprazole and HPBCD.
PB  - Springer, New York
T2  - AAPS PharmSciTech
T1  - Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique
VL  - 13
IS  - 2
SP  - 623
EP  - 631
DO  - 10.1208/s12249-012-9786-3
ER  - 

@article{
author = "Mihajlović, Tijana and Kachrimanis, Kyriakos and Graovac, Adrijana and Đurić, Zorica and Ibrić, Svetlana",
year = "2012",
abstract = "Due to the fact that the number of new poorly soluble active pharmaceutical ingredients is increasing, it is important to investigate the possibilities of improvement of their solubility in order to obtain a final pharmaceutical formulation with enhanced bioavailability. One of the strategies to increase drug solubility is the inclusion of the APIs in cyclodextrins. The aim of this study was to investigate the possibility of aripiprazole solubility improvement by inclusion in (2-hydroxy)propyl-beta-cyclodextrin (HPBCD) and simultaneous manipulation of pH of the medium and addition of polyvinylpyrrolidone. Aripiprazole-HPBCD complexes were prepared by spray drying aqueous drug-HPBCD solutions, and their properties were compared with those prepared by solvent-drop co-grinding and physical mixing. The obtained powders were characterized by thermoanalytical methods (TGA and DSC), FTIR spectroscopy, their dissolution properties were assessed, while the binding of aripiprazole into the cavity of HPBCD was studied by molecular docking simulations. The solubilization capacity was found to be dependent on pH as well as the buffer solution's ionic composition. The presence of PVP in the formulation could affect the solubilization capacity significantly, but further experimentation is required before its effect is fully understood. On the basis of solubility studies, the drug/HPBCD stoichiometry was found to be 1:3. The spray-dried products were free of crystalline aripiprazole, they possessed higher solubility and dissolution rate, and were stable enough over a prolonged period of storage. Spray drying of cyclodextrin solutions proved to be an appropriate and efficient technique for the preparation of highly soluble inclusion compounds of aripiprazole and HPBCD.",
publisher = "Springer, New York",
journal = "AAPS PharmSciTech",
title = "Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique",
volume = "13",
number = "2",
pages = "623-631",
doi = "10.1208/s12249-012-9786-3"
}

Mihajlović, T., Kachrimanis, K., Graovac, A., Đurić, Z.,& Ibrić, S.. (2012). Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique. in AAPS PharmSciTech
Springer, New York., 13(2), 623-631.
https://doi.org/10.1208/s12249-012-9786-3

Mihajlović T, Kachrimanis K, Graovac A, Đurić Z, Ibrić S. Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique. in AAPS PharmSciTech. 2012;13(2):623-631.
doi:10.1208/s12249-012-9786-3 .

Mihajlović, Tijana, Kachrimanis, Kyriakos, Graovac, Adrijana, Đurić, Zorica, Ibrić, Svetlana, "Improvement of Aripiprazole Solubility by Complexation with (2-Hydroxy)propyl-beta-cyclodextrin Using Spray Drying Technique" in AAPS PharmSciTech, 13, no. 2 (2012):623-631,
https://doi.org/10.1208/s12249-012-9786-3 . .

TY  - JOUR
AU  - Kolasinac, Nemanja
AU  - Kachrimanis, Kyriakos
AU  - Homšek, Irena
AU  - Grujić, Branka
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1640
AB  - The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of the poorly water soluble drug substance desloratadine that can be used for the preparation of immediate release tablet formulation. Two commercially available poloxamer grades (poloxamer P 188 and poloxamer P 407) were selected, and solid dispersions (SDs) containing different weight ratio of poloxamers and desloratadine were prepared by a low temperature melting method. All SDs were subjected to basic physicochemical characterization by thermal and vibrational spectroscopy methods in order to evaluate the efficiency of poloxamers as solubility enhancers. Immediate release tablets were prepared by direct compression of powdered solid dispersions according to a General Factorial Design, in order to evaluate the statistical significance of two formulation (X-1 - type of poloxamer in SD and X-2 - poloxamer ratio in SD) and one process variable (X-3 - compression force) on the drug dissolution rate. It was found that desloratadine in SDs existed in the amorphous state, and that can be largely responsible for the enhanced intrinsic solubility, which was more pronounced in SDs containing poloxamer 188. Statistical analysis of the factorial design revealed that both investigated formulation variables exert a significant effect on the drug dissolution rate. Increased poloxamer ratio in SDs resulted in increased drug dissolution rate, with poloxamer 188 contributing to a faster dissolution rate than poloxamer 407, in accordance with the results of intrinsic dissolution tests. Moreover, there is a significant interaction between poloxamer ratio in SD and compression force. Higher poloxamer ratio in SDs and higher compression force results in a significant decrease of the drug dissolution rate, which can be attributed to the lower porosity of the tablets and more pronounced bonding between poloxamer particles.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Solubility enhancement of desloratadine by solid dispersion in poloxamers
VL  - 436
IS  - 1-2
SP  - 161
EP  - 170
DO  - 10.1016/j.ijpharm.2012.06.060
ER  - 

@article{
author = "Kolasinac, Nemanja and Kachrimanis, Kyriakos and Homšek, Irena and Grujić, Branka and Đurić, Zorica and Ibrić, Svetlana",
year = "2012",
abstract = "The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of the poorly water soluble drug substance desloratadine that can be used for the preparation of immediate release tablet formulation. Two commercially available poloxamer grades (poloxamer P 188 and poloxamer P 407) were selected, and solid dispersions (SDs) containing different weight ratio of poloxamers and desloratadine were prepared by a low temperature melting method. All SDs were subjected to basic physicochemical characterization by thermal and vibrational spectroscopy methods in order to evaluate the efficiency of poloxamers as solubility enhancers. Immediate release tablets were prepared by direct compression of powdered solid dispersions according to a General Factorial Design, in order to evaluate the statistical significance of two formulation (X-1 - type of poloxamer in SD and X-2 - poloxamer ratio in SD) and one process variable (X-3 - compression force) on the drug dissolution rate. It was found that desloratadine in SDs existed in the amorphous state, and that can be largely responsible for the enhanced intrinsic solubility, which was more pronounced in SDs containing poloxamer 188. Statistical analysis of the factorial design revealed that both investigated formulation variables exert a significant effect on the drug dissolution rate. Increased poloxamer ratio in SDs resulted in increased drug dissolution rate, with poloxamer 188 contributing to a faster dissolution rate than poloxamer 407, in accordance with the results of intrinsic dissolution tests. Moreover, there is a significant interaction between poloxamer ratio in SD and compression force. Higher poloxamer ratio in SDs and higher compression force results in a significant decrease of the drug dissolution rate, which can be attributed to the lower porosity of the tablets and more pronounced bonding between poloxamer particles.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Solubility enhancement of desloratadine by solid dispersion in poloxamers",
volume = "436",
number = "1-2",
pages = "161-170",
doi = "10.1016/j.ijpharm.2012.06.060"
}

Kolasinac, N., Kachrimanis, K., Homšek, I., Grujić, B., Đurić, Z.,& Ibrić, S.. (2012). Solubility enhancement of desloratadine by solid dispersion in poloxamers. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 436(1-2), 161-170.
https://doi.org/10.1016/j.ijpharm.2012.06.060

Kolasinac N, Kachrimanis K, Homšek I, Grujić B, Đurić Z, Ibrić S. Solubility enhancement of desloratadine by solid dispersion in poloxamers. in International Journal of Pharmaceutics. 2012;436(1-2):161-170.
doi:10.1016/j.ijpharm.2012.06.060 .

Kolasinac, Nemanja, Kachrimanis, Kyriakos, Homšek, Irena, Grujić, Branka, Đurić, Zorica, Ibrić, Svetlana, "Solubility enhancement of desloratadine by solid dispersion in poloxamers" in International Journal of Pharmaceutics, 436, no. 1-2 (2012):161-170,
https://doi.org/10.1016/j.ijpharm.2012.06.060 . .