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  - 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 . .