TY  - JOUR
AU  - Vulović, Aleksandra
AU  - Sustersić, Tijana
AU  - Cvijić, Sandra
AU  - Ibrić, Svetlana
AU  - Filipović, Nenad
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3186
AB  - One of the critical components of the respiratory drug delivery is the manner in which the inhaled aerosol is deposited in respiratory tract compartments. Depending on formulation properties, device characteristics and breathing pattern, only a certain fraction of the dose will reach the target site in the lungs, while the rest of the drug will deposit in the inhalation device or in the mouth-throat region. The aim of this study was to link the Computational fluid dynamics (CFD) with physiologically-based pharmacokinetic (PBPK) modelling in order to predict aerolisolization of different dry powder formulations, and estimate concomitant in vivo deposition and absorption of amiloride hydrochloride. Drug physicochemical properties were experimentally determined and used as inputs for the CFD simulations of particle flow in the generated 3D geometric model of Aerolizer (R) dry powder inhaler (DPI). CFD simulations were used to simulate air flow through Aerolizer (R) inhaler and Discrete Phase Method (DPM) was used to simulate aerosol particles deposition within the fluid domain. The simulated values for the percent emitted dose were comparable to the values obtained using Andersen cascade impactor (ACI). However, CFD predictions indicated that aerosolized DPI have smaller particle size and narrower size distribution than assumed based on ACI measurements. Comparison with the literature in vivo data revealed that the constructed drug-specific PBPK model was able to capture amiloride absorption pattern following oral and inhalation administration. The PBPK simulation results, based on the CFD generated particle distribution data as input, illustrated the influence of formulation properties on the expected drug plasma concentration profiles. The model also predicted the influence of potential changes in physiological parameters on the extent of inhaled amiloride absorption. Overall, this study demonstrated the potential of the combined CFD-PBPK approach to model inhaled drug bioperformance, and suggested that CFD generated results might serve as input for the prediction of drug deposition pattern in vivo.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modelling
VL  - 113
SP  - 171
EP  - 184
DO  - 10.1016/j.ejps.2017.10.022
ER  - 

@article{
author = "Vulović, Aleksandra and Sustersić, Tijana and Cvijić, Sandra and Ibrić, Svetlana and Filipović, Nenad",
year = "2018",
abstract = "One of the critical components of the respiratory drug delivery is the manner in which the inhaled aerosol is deposited in respiratory tract compartments. Depending on formulation properties, device characteristics and breathing pattern, only a certain fraction of the dose will reach the target site in the lungs, while the rest of the drug will deposit in the inhalation device or in the mouth-throat region. The aim of this study was to link the Computational fluid dynamics (CFD) with physiologically-based pharmacokinetic (PBPK) modelling in order to predict aerolisolization of different dry powder formulations, and estimate concomitant in vivo deposition and absorption of amiloride hydrochloride. Drug physicochemical properties were experimentally determined and used as inputs for the CFD simulations of particle flow in the generated 3D geometric model of Aerolizer (R) dry powder inhaler (DPI). CFD simulations were used to simulate air flow through Aerolizer (R) inhaler and Discrete Phase Method (DPM) was used to simulate aerosol particles deposition within the fluid domain. The simulated values for the percent emitted dose were comparable to the values obtained using Andersen cascade impactor (ACI). However, CFD predictions indicated that aerosolized DPI have smaller particle size and narrower size distribution than assumed based on ACI measurements. Comparison with the literature in vivo data revealed that the constructed drug-specific PBPK model was able to capture amiloride absorption pattern following oral and inhalation administration. The PBPK simulation results, based on the CFD generated particle distribution data as input, illustrated the influence of formulation properties on the expected drug plasma concentration profiles. The model also predicted the influence of potential changes in physiological parameters on the extent of inhaled amiloride absorption. Overall, this study demonstrated the potential of the combined CFD-PBPK approach to model inhaled drug bioperformance, and suggested that CFD generated results might serve as input for the prediction of drug deposition pattern in vivo.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modelling",
volume = "113",
pages = "171-184",
doi = "10.1016/j.ejps.2017.10.022"
}

Vulović, A., Sustersić, T., Cvijić, S., Ibrić, S.,& Filipović, N.. (2018). Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modelling. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 113, 171-184.
https://doi.org/10.1016/j.ejps.2017.10.022

Vulović A, Sustersić T, Cvijić S, Ibrić S, Filipović N. Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modelling. in European Journal of Pharmaceutical Sciences. 2018;113:171-184.
doi:10.1016/j.ejps.2017.10.022 .

Vulović, Aleksandra, Sustersić, Tijana, Cvijić, Sandra, Ibrić, Svetlana, Filipović, Nenad, "Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modelling" in European Journal of Pharmaceutical Sciences, 113 (2018):171-184,
https://doi.org/10.1016/j.ejps.2017.10.022 . .

TY  - CONF
AU  - Sustersić, Tijana
AU  - Vulović, Aleksandra
AU  - Filipović, Nenad
AU  - Cvijić, Sandra
AU  - Ibrić, Svetlana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3106
AB  - Aim of this study was to analyze how modifications in circulation chamber dimensions affect aerosol particle deposition in a Dry Powder Inhaler (DPI) Aerolizer. Combining computational fluid dynamics (CFD), for simulation of fluid flow (air), with discrete phase model (DPM) for particles simulation, we can better understand particle dispersion within inhaler's air flow field. Input in the simulation was 20mg of aerosol particles with initial velocity of 11,79166m/s. Dimension change influences maximum velocities, as well as percentage of deposited particles. Based on these information we were able to calculate the number of particles on the outlet and compare efficiency reduction when circulation chamber height increased. Knowledge obtained in this way can help in device performance optimization.
PB  - Institute of Electrical and Electronics Engineers Inc.
C3  - Proceedings - 2017 IEEE 17th International Conference on Bioinformatics and Bioengineering, BIBE 201
T1  - Effect of Circulation Chamber Dimensions on Aerosol Delivery Efficiency of a Commertial Dry Powder Inhaler Aerolizer (R)
SP  - 555
EP  - 558
DO  - 10.1109/BIBE.2017.00011
ER  - 

@conference{
author = "Sustersić, Tijana and Vulović, Aleksandra and Filipović, Nenad and Cvijić, Sandra and Ibrić, Svetlana",
year = "2018",
abstract = "Aim of this study was to analyze how modifications in circulation chamber dimensions affect aerosol particle deposition in a Dry Powder Inhaler (DPI) Aerolizer. Combining computational fluid dynamics (CFD), for simulation of fluid flow (air), with discrete phase model (DPM) for particles simulation, we can better understand particle dispersion within inhaler's air flow field. Input in the simulation was 20mg of aerosol particles with initial velocity of 11,79166m/s. Dimension change influences maximum velocities, as well as percentage of deposited particles. Based on these information we were able to calculate the number of particles on the outlet and compare efficiency reduction when circulation chamber height increased. Knowledge obtained in this way can help in device performance optimization.",
publisher = "Institute of Electrical and Electronics Engineers Inc.",
journal = "Proceedings - 2017 IEEE 17th International Conference on Bioinformatics and Bioengineering, BIBE 201",
title = "Effect of Circulation Chamber Dimensions on Aerosol Delivery Efficiency of a Commertial Dry Powder Inhaler Aerolizer (R)",
pages = "555-558",
doi = "10.1109/BIBE.2017.00011"
}

Sustersić, T., Vulović, A., Filipović, N., Cvijić, S.,& Ibrić, S.. (2018). Effect of Circulation Chamber Dimensions on Aerosol Delivery Efficiency of a Commertial Dry Powder Inhaler Aerolizer (R). in Proceedings - 2017 IEEE 17th International Conference on Bioinformatics and Bioengineering, BIBE 201
Institute of Electrical and Electronics Engineers Inc.., 555-558.
https://doi.org/10.1109/BIBE.2017.00011

Sustersić T, Vulović A, Filipović N, Cvijić S, Ibrić S. Effect of Circulation Chamber Dimensions on Aerosol Delivery Efficiency of a Commertial Dry Powder Inhaler Aerolizer (R). in Proceedings - 2017 IEEE 17th International Conference on Bioinformatics and Bioengineering, BIBE 201. 2018;:555-558.
doi:10.1109/BIBE.2017.00011 .

Sustersić, Tijana, Vulović, Aleksandra, Filipović, Nenad, Cvijić, Sandra, Ibrić, Svetlana, "Effect of Circulation Chamber Dimensions on Aerosol Delivery Efficiency of a Commertial Dry Powder Inhaler Aerolizer (R)" in Proceedings - 2017 IEEE 17th International Conference on Bioinformatics and Bioengineering, BIBE 201 (2018):555-558,
https://doi.org/10.1109/BIBE.2017.00011 . .

TY  - JOUR
AU  - Velaga, Sitaram P.
AU  - Đuriš, Jelena
AU  - Cvijić, Sandra
AU  - Rozou, Stavroula
AU  - Russo, Paola
AU  - Colombo, Gaia
AU  - Rossi, Alessandra
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3187
AB  - In vitro dissolution testing is routinely used in the development of pharmaceutical products. Whilst the dissolution testing methods are well established and standardized for oral dosage forms, i.e. tablets and capsules, there are no pharmacopoeia methods or regulatory requirements for testing the dissolution of orally inhaled powders. Despite this, a wide variety of dissolution testing methods for orally inhaled powders has been developed and their bio-relevance has been evaluated. This review provides an overview of the in vitro dissolution methodologies for dry inhalation products, with particular emphasis on dry powder inhalers, where the dissolution behavior of the respirable particles can have a role on duration and absorption of the drug. Dissolution mechanisms of respirable particles as well as kinetic models have been presented. A more recent biorelevant dissolution set-ups and media for studying inhalation biopharmaceutics were also reviewed. In addition, factors affecting interplay between dissolution and absorption of deposited particles in the context of biopharmaceutical considerations of inhalation products were examined.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Dry powder inhalers: An overview of the in vitro dissolution methodologies and their correlation with the biopharmaceutical aspects of the drug products
VL  - 113
SP  - 18
EP  - 28
DO  - 10.1016/j.ejps.2017.09.002
ER  - 

@article{
author = "Velaga, Sitaram P. and Đuriš, Jelena and Cvijić, Sandra and Rozou, Stavroula and Russo, Paola and Colombo, Gaia and Rossi, Alessandra",
year = "2018",
abstract = "In vitro dissolution testing is routinely used in the development of pharmaceutical products. Whilst the dissolution testing methods are well established and standardized for oral dosage forms, i.e. tablets and capsules, there are no pharmacopoeia methods or regulatory requirements for testing the dissolution of orally inhaled powders. Despite this, a wide variety of dissolution testing methods for orally inhaled powders has been developed and their bio-relevance has been evaluated. This review provides an overview of the in vitro dissolution methodologies for dry inhalation products, with particular emphasis on dry powder inhalers, where the dissolution behavior of the respirable particles can have a role on duration and absorption of the drug. Dissolution mechanisms of respirable particles as well as kinetic models have been presented. A more recent biorelevant dissolution set-ups and media for studying inhalation biopharmaceutics were also reviewed. In addition, factors affecting interplay between dissolution and absorption of deposited particles in the context of biopharmaceutical considerations of inhalation products were examined.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Dry powder inhalers: An overview of the in vitro dissolution methodologies and their correlation with the biopharmaceutical aspects of the drug products",
volume = "113",
pages = "18-28",
doi = "10.1016/j.ejps.2017.09.002"
}

Velaga, S. P., Đuriš, J., Cvijić, S., Rozou, S., Russo, P., Colombo, G.,& Rossi, A.. (2018). Dry powder inhalers: An overview of the in vitro dissolution methodologies and their correlation with the biopharmaceutical aspects of the drug products. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 113, 18-28.
https://doi.org/10.1016/j.ejps.2017.09.002

Velaga SP, Đuriš J, Cvijić S, Rozou S, Russo P, Colombo G, Rossi A. Dry powder inhalers: An overview of the in vitro dissolution methodologies and their correlation with the biopharmaceutical aspects of the drug products. in European Journal of Pharmaceutical Sciences. 2018;113:18-28.
doi:10.1016/j.ejps.2017.09.002 .

Velaga, Sitaram P., Đuriš, Jelena, Cvijić, Sandra, Rozou, Stavroula, Russo, Paola, Colombo, Gaia, Rossi, Alessandra, "Dry powder inhalers: An overview of the in vitro dissolution methodologies and their correlation with the biopharmaceutical aspects of the drug products" in European Journal of Pharmaceutical Sciences, 113 (2018):18-28,
https://doi.org/10.1016/j.ejps.2017.09.002 . .