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  - Mihajlović, Tijana
AU  - Ibrić, Svetlana
AU  - Mladenović, Aleksandar
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1468
AB  - The aim of this study was to investigate the effect of changing spray-drying parameters on the production of a naratriptan/maltodextrin/lactose composite, as well as to evaluate the application of design of experiments and multilayer perceptron (MLP) neural network in studying the spray-drying process. The system was spray dried as an aqueous solution using a Buchi 290-Mini Spray Dryer (Buchi Laboratoriums-Technik AG, Switzerland). A 2(4-1) factorial design study was undertaken to select the spray-drying processing variables that significantly affect the production yield, outlet air temperature, and residual moisture content. The process parameters studied were inlet air temperature, pump speed, aspirator setting (drying air flow rate), and feed concentration. After performing this screening study, three process parameters, pump speed, inlet air temperature, and feed concentration, were selected for further analysis, applying a central composite design and artificial neural network. Overall, the parameter that had the greatest influence on each investigated response was pump speed. It significantly influenced yield, moisture content, and particle size. Interaction between inlet air temperature and feed concentration was the only statistically significant interaction that influenced the moisture content. Particle size was mostly influenced by feed concentration as well as by a pump speed. A multilayer perceptron was the type of artificial neural network applied. The selected MLP structure had three layers: the first layer had three input units, the second layer had three hidden units, and the third layer had four output units. The selected MLP was trained through 10,000 epochs. Design of experiments using response surface methodology allows insight into interactions between variables, and an artificial neural network provides better prediction potential, enabling simultaneously determination of several outputs. Design of experiments and artificial neural network proved to be useful tool for optimization of the spray-drying process, where a design space for achieving the best process yields and optimum particle characteristics was established. There is a possibility that this conclusion can be drawn for other maltodextrin/lactose systems with other drug substances or for other similar spray-dried systems (the feedstock type is a carbohydrate-based aqueous solution). In future work, this will be tested with other materials.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Drying Technology
T1  - Application of Design of Experiments and Multilayer Perceptron Neural Network in Optimization of the Spray-Drying Process
VL  - 29
IS  - 14
SP  - 1638
EP  - 1647
DO  - 10.1080/07373937.2011.592960
ER  - 

@article{
author = "Mihajlović, Tijana and Ibrić, Svetlana and Mladenović, Aleksandar",
year = "2011",
abstract = "The aim of this study was to investigate the effect of changing spray-drying parameters on the production of a naratriptan/maltodextrin/lactose composite, as well as to evaluate the application of design of experiments and multilayer perceptron (MLP) neural network in studying the spray-drying process. The system was spray dried as an aqueous solution using a Buchi 290-Mini Spray Dryer (Buchi Laboratoriums-Technik AG, Switzerland). A 2(4-1) factorial design study was undertaken to select the spray-drying processing variables that significantly affect the production yield, outlet air temperature, and residual moisture content. The process parameters studied were inlet air temperature, pump speed, aspirator setting (drying air flow rate), and feed concentration. After performing this screening study, three process parameters, pump speed, inlet air temperature, and feed concentration, were selected for further analysis, applying a central composite design and artificial neural network. Overall, the parameter that had the greatest influence on each investigated response was pump speed. It significantly influenced yield, moisture content, and particle size. Interaction between inlet air temperature and feed concentration was the only statistically significant interaction that influenced the moisture content. Particle size was mostly influenced by feed concentration as well as by a pump speed. A multilayer perceptron was the type of artificial neural network applied. The selected MLP structure had three layers: the first layer had three input units, the second layer had three hidden units, and the third layer had four output units. The selected MLP was trained through 10,000 epochs. Design of experiments using response surface methodology allows insight into interactions between variables, and an artificial neural network provides better prediction potential, enabling simultaneously determination of several outputs. Design of experiments and artificial neural network proved to be useful tool for optimization of the spray-drying process, where a design space for achieving the best process yields and optimum particle characteristics was established. There is a possibility that this conclusion can be drawn for other maltodextrin/lactose systems with other drug substances or for other similar spray-dried systems (the feedstock type is a carbohydrate-based aqueous solution). In future work, this will be tested with other materials.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Drying Technology",
title = "Application of Design of Experiments and Multilayer Perceptron Neural Network in Optimization of the Spray-Drying Process",
volume = "29",
number = "14",
pages = "1638-1647",
doi = "10.1080/07373937.2011.592960"
}

Mihajlović, T., Ibrić, S.,& Mladenović, A.. (2011). Application of Design of Experiments and Multilayer Perceptron Neural Network in Optimization of the Spray-Drying Process. in Drying Technology
Taylor & Francis Inc, Philadelphia., 29(14), 1638-1647.
https://doi.org/10.1080/07373937.2011.592960

Mihajlović T, Ibrić S, Mladenović A. Application of Design of Experiments and Multilayer Perceptron Neural Network in Optimization of the Spray-Drying Process. in Drying Technology. 2011;29(14):1638-1647.
doi:10.1080/07373937.2011.592960 .

Mihajlović, Tijana, Ibrić, Svetlana, Mladenović, Aleksandar, "Application of Design of Experiments and Multilayer Perceptron Neural Network in Optimization of the Spray-Drying Process" in Drying Technology, 29, no. 14 (2011):1638-1647,
https://doi.org/10.1080/07373937.2011.592960 . .