TY  - JOUR
AU  - Nikolić, Ines
AU  - Lunter, Dominique
AU  - Ranđelović, Danijela
AU  - Žugić, Ana R.
AU  - Tadić, Vanja M.
AU  - Marković, Bojan
AU  - Cekić, Nebojša
AU  - Živković, Lada
AU  - Topalović, Dijana
AU  - Potparević, Biljana
AU  - Daniels, Rolf
AU  - Savić, Snežana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3084
AB  - The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI  lt  0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/ mL) and FRAP (1.19 +/- 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application
VL  - 550
IS  - 1-2
SP  - 333
EP  - 346
DO  - 10.1016/j.ijpharm.2018.08.060
ER  - 

@article{
author = "Nikolić, Ines and Lunter, Dominique and Ranđelović, Danijela and Žugić, Ana R. and Tadić, Vanja M. and Marković, Bojan and Cekić, Nebojša and Živković, Lada and Topalović, Dijana and Potparević, Biljana and Daniels, Rolf and Savić, Snežana",
year = "2018",
abstract = "The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI  lt  0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/ mL) and FRAP (1.19 +/- 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application",
volume = "550",
number = "1-2",
pages = "333-346",
doi = "10.1016/j.ijpharm.2018.08.060"
}

Nikolić, I., Lunter, D., Ranđelović, D., Žugić, A. R., Tadić, V. M., Marković, B., Cekić, N., Živković, L., Topalović, D., Potparević, B., Daniels, R.,& Savić, S.. (2018). Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 550(1-2), 333-346.
https://doi.org/10.1016/j.ijpharm.2018.08.060

Nikolić I, Lunter D, Ranđelović D, Žugić AR, Tadić VM, Marković B, Cekić N, Živković L, Topalović D, Potparević B, Daniels R, Savić S. Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application. in International Journal of Pharmaceutics. 2018;550(1-2):333-346.
doi:10.1016/j.ijpharm.2018.08.060 .

Nikolić, Ines, Lunter, Dominique, Ranđelović, Danijela, Žugić, Ana R., Tadić, Vanja M., Marković, Bojan, Cekić, Nebojša, Živković, Lada, Topalović, Dijana, Potparević, Biljana, Daniels, Rolf, Savić, Snežana, "Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application" in International Journal of Pharmaceutics, 550, no. 1-2 (2018):333-346,
https://doi.org/10.1016/j.ijpharm.2018.08.060 . .

TY  - JOUR
AU  - Ilić, Tanja
AU  - Pantelić, Ivana
AU  - Lunter, Dominique
AU  - Dodević, Sanela
AU  - Marković, Bojan
AU  - Ranković, Dragana
AU  - Daniels, Rolf
AU  - Savić, Snežana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2826
AB  - This work aimed to prove the ability of "ready-to-use" topical vehicles based on alkyl polyglucoside-mixed emulsifier (with/without co-solvent modifications) to replace the conventionally used pharmacopoeial bases (e.g., non-ionic hydrophilic cream) in compounding practice. For this purpose, considering the regulatory efforts to establish alternative, scientifically valid methods for evaluating therapeutic equivalence of topical semisolids, we performed a comparative assessment of microstructure, selected critical quality attributes (CQAs) and in vitro/in vivo product performances, by utilizing aceclofenac as a model drug. The differences in composition between investigated samples have imposed remarkable variances in monitored CQAs (particularly in the amount of aceclofenac dissolved, rheological properties and water distribution mode), reflecting the distinct differences in microstructure formed, as partially observed by polarization microscopy and confocal Raman spectral imaging. Although not fully indicative of the in vivo performances, in vitro release data (vertical diffusion vs. immersion cells) proved the microstructure peculiarities, asserting the rheological properties as decisive factor for obtained liberation profiles. Contrary, in vitro permeation results obtained using pig ear epidermis correlated well with in vivo dermatopharmacokinetic data and distinguished unequivocally between tested formulations, emphasizing the importance of skin/vehicle interactions. In summary, suggested multi-faceted approach can provide adequate proof on topical semisolids therapeutic equivalence or lack thereof.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Critical quality attributes, in vitro release and correlated in vitro skin permeation-in vivo tape stripping collective data for demonstrating therapeutic (non) equivalence of topical semisolids: A case study of "ready-to-use" vehicles
VL  - 528
IS  - 1-2
SP  - 253
EP  - 267
DO  - 10.1016/j.ijpharm.2017.06.018
ER  - 

@article{
author = "Ilić, Tanja and Pantelić, Ivana and Lunter, Dominique and Dodević, Sanela and Marković, Bojan and Ranković, Dragana and Daniels, Rolf and Savić, Snežana",
year = "2017",
abstract = "This work aimed to prove the ability of "ready-to-use" topical vehicles based on alkyl polyglucoside-mixed emulsifier (with/without co-solvent modifications) to replace the conventionally used pharmacopoeial bases (e.g., non-ionic hydrophilic cream) in compounding practice. For this purpose, considering the regulatory efforts to establish alternative, scientifically valid methods for evaluating therapeutic equivalence of topical semisolids, we performed a comparative assessment of microstructure, selected critical quality attributes (CQAs) and in vitro/in vivo product performances, by utilizing aceclofenac as a model drug. The differences in composition between investigated samples have imposed remarkable variances in monitored CQAs (particularly in the amount of aceclofenac dissolved, rheological properties and water distribution mode), reflecting the distinct differences in microstructure formed, as partially observed by polarization microscopy and confocal Raman spectral imaging. Although not fully indicative of the in vivo performances, in vitro release data (vertical diffusion vs. immersion cells) proved the microstructure peculiarities, asserting the rheological properties as decisive factor for obtained liberation profiles. Contrary, in vitro permeation results obtained using pig ear epidermis correlated well with in vivo dermatopharmacokinetic data and distinguished unequivocally between tested formulations, emphasizing the importance of skin/vehicle interactions. In summary, suggested multi-faceted approach can provide adequate proof on topical semisolids therapeutic equivalence or lack thereof.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Critical quality attributes, in vitro release and correlated in vitro skin permeation-in vivo tape stripping collective data for demonstrating therapeutic (non) equivalence of topical semisolids: A case study of "ready-to-use" vehicles",
volume = "528",
number = "1-2",
pages = "253-267",
doi = "10.1016/j.ijpharm.2017.06.018"
}

Ilić, T., Pantelić, I., Lunter, D., Dodević, S., Marković, B., Ranković, D., Daniels, R.,& Savić, S.. (2017). Critical quality attributes, in vitro release and correlated in vitro skin permeation-in vivo tape stripping collective data for demonstrating therapeutic (non) equivalence of topical semisolids: A case study of "ready-to-use" vehicles. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 528(1-2), 253-267.
https://doi.org/10.1016/j.ijpharm.2017.06.018

Ilić T, Pantelić I, Lunter D, Dodević S, Marković B, Ranković D, Daniels R, Savić S. Critical quality attributes, in vitro release and correlated in vitro skin permeation-in vivo tape stripping collective data for demonstrating therapeutic (non) equivalence of topical semisolids: A case study of "ready-to-use" vehicles. in International Journal of Pharmaceutics. 2017;528(1-2):253-267.
doi:10.1016/j.ijpharm.2017.06.018 .

Ilić, Tanja, Pantelić, Ivana, Lunter, Dominique, Dodević, Sanela, Marković, Bojan, Ranković, Dragana, Daniels, Rolf, Savić, Snežana, "Critical quality attributes, in vitro release and correlated in vitro skin permeation-in vivo tape stripping collective data for demonstrating therapeutic (non) equivalence of topical semisolids: A case study of "ready-to-use" vehicles" in International Journal of Pharmaceutics, 528, no. 1-2 (2017):253-267,
https://doi.org/10.1016/j.ijpharm.2017.06.018 . .

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Kleinebudde, Peter
AU  - Đuriš, Jelena
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2568
AB  - This study for the first time demonstrates combined application of mixture experimental design and artificial neural networks (ANNs) in the solid dispersions (SDs) development. Ternary carbamazepine-Soluplus (R)-poloxamer 188 SDs were prepared by solvent casting method to improve carbamazepine dissolution rate. The influence of the composition of prepared SDs on carbamazepine dissolution rate was evaluated using d-optimal mixture experimental design and multilayer perceptron ANNs. Physicochemical characterization proved the presence of the most stable carbamazepine polymorph III within the SD matrix. Ternary carbamazepine-Soluplus (R)-poloxamer 188 SDs significantly improved carbamazepine dissolution rate compared to pure drug. Models developed by ANNs and mixture experimental design well described the relationship between proportions of SD components and percentage of carbamazepine released after 10 (Q(10)) and 20 (Q(20)) min, wherein ANN model exhibit better predictability on test data set. Proportions of carbamazepine and poloxamer 188 exhibited the highest influence on carbamazepine release rate. The highest carbamazepine release rate was observed for SDs with the lowest proportions of carbamazepine and the highest proportions of poloxamer 188. ANNs and mixture experimental design can be used as powerful data modeling tools in the systematic development of SDs. Taking into account advantages and disadvantages of both techniques, their combined application should be encouraged.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Drug Development and Industrial Pharmacy
T1  - Combined application of mixture experimental design and artificial neural networks in the solid dispersion development
VL  - 42
IS  - 3
SP  - 389
EP  - 402
DO  - 10.3109/03639045.2015.1054831
ER  - 

@article{
author = "Medarević, Đorđe and Kleinebudde, Peter and Đuriš, Jelena and Đurić, Zorica and Ibrić, Svetlana",
year = "2016",
abstract = "This study for the first time demonstrates combined application of mixture experimental design and artificial neural networks (ANNs) in the solid dispersions (SDs) development. Ternary carbamazepine-Soluplus (R)-poloxamer 188 SDs were prepared by solvent casting method to improve carbamazepine dissolution rate. The influence of the composition of prepared SDs on carbamazepine dissolution rate was evaluated using d-optimal mixture experimental design and multilayer perceptron ANNs. Physicochemical characterization proved the presence of the most stable carbamazepine polymorph III within the SD matrix. Ternary carbamazepine-Soluplus (R)-poloxamer 188 SDs significantly improved carbamazepine dissolution rate compared to pure drug. Models developed by ANNs and mixture experimental design well described the relationship between proportions of SD components and percentage of carbamazepine released after 10 (Q(10)) and 20 (Q(20)) min, wherein ANN model exhibit better predictability on test data set. Proportions of carbamazepine and poloxamer 188 exhibited the highest influence on carbamazepine release rate. The highest carbamazepine release rate was observed for SDs with the lowest proportions of carbamazepine and the highest proportions of poloxamer 188. ANNs and mixture experimental design can be used as powerful data modeling tools in the systematic development of SDs. Taking into account advantages and disadvantages of both techniques, their combined application should be encouraged.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Drug Development and Industrial Pharmacy",
title = "Combined application of mixture experimental design and artificial neural networks in the solid dispersion development",
volume = "42",
number = "3",
pages = "389-402",
doi = "10.3109/03639045.2015.1054831"
}

Medarević, Đ., Kleinebudde, P., Đuriš, J., Đurić, Z.,& Ibrić, S.. (2016). Combined application of mixture experimental design and artificial neural networks in the solid dispersion development. in Drug Development and Industrial Pharmacy
Taylor & Francis Ltd, Abingdon., 42(3), 389-402.
https://doi.org/10.3109/03639045.2015.1054831

Medarević Đ, Kleinebudde P, Đuriš J, Đurić Z, Ibrić S. Combined application of mixture experimental design and artificial neural networks in the solid dispersion development. in Drug Development and Industrial Pharmacy. 2016;42(3):389-402.
doi:10.3109/03639045.2015.1054831 .

Medarević, Đorđe, Kleinebudde, Peter, Đuriš, Jelena, Đurić, Zorica, Ibrić, Svetlana, "Combined application of mixture experimental design and artificial neural networks in the solid dispersion development" in Drug Development and Industrial Pharmacy, 42, no. 3 (2016):389-402,
https://doi.org/10.3109/03639045.2015.1054831 . .