TY  - JOUR
AU  - Cvijić, Sandra
AU  - Parojčić, Jelena
AU  - Langguth, Peter
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2210
AB  - Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence of food is one of the key factors limiting oral absorption of drugs with limited permeability and absorption restricted to the upper parts of the intestine, while having negligible effect on pharmacokinetic profile of drugs with pH- and site-independent absorption. Dissolution medium pH 4.6 with the addition of hydroxypropyl methylcellulose was suggested to simulate postprandial gastric conditions for drugs whose solubility under these conditions is not the limiting factor for drug absorption. In addition, drug formulation was found to be an interfering factor in relation to the impact of medium viscosity on the rate and extent of drug absorption.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification
VL  - 61
SP  - 40
EP  - 53
DO  - 10.1016/j.ejps.2014.04.008
ER  - 

@article{
author = "Cvijić, Sandra and Parojčić, Jelena and Langguth, Peter",
year = "2014",
abstract = "Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence of food is one of the key factors limiting oral absorption of drugs with limited permeability and absorption restricted to the upper parts of the intestine, while having negligible effect on pharmacokinetic profile of drugs with pH- and site-independent absorption. Dissolution medium pH 4.6 with the addition of hydroxypropyl methylcellulose was suggested to simulate postprandial gastric conditions for drugs whose solubility under these conditions is not the limiting factor for drug absorption. In addition, drug formulation was found to be an interfering factor in relation to the impact of medium viscosity on the rate and extent of drug absorption.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification",
volume = "61",
pages = "40-53",
doi = "10.1016/j.ejps.2014.04.008"
}

Cvijić, S., Parojčić, J.,& Langguth, P.. (2014). Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 61, 40-53.
https://doi.org/10.1016/j.ejps.2014.04.008

Cvijić S, Parojčić J, Langguth P. Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification. in European Journal of Pharmaceutical Sciences. 2014;61:40-53.
doi:10.1016/j.ejps.2014.04.008 .

Cvijić, Sandra, Parojčić, Jelena, Langguth, Peter, "Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification" in European Journal of Pharmaceutical Sciences, 61 (2014):40-53,
https://doi.org/10.1016/j.ejps.2014.04.008 . .

TY  - JOUR
AU  - Cvijić, Sandra
AU  - Langguth, Peter
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2108
AB  - The purpose of this study was to mechanistically interpret the oral absorption pattern of trospium in fasted and fed states by means of gastrointestinal simulation technology. A drug absorption model was built on the basis of experimental data. According to the generated model, low permeability across the intestinal epithelium, delayed gastric emptying time and a prolonged residence time in the small intestine are the key factors governing trospium absorption in the fasted state. Furthermore, in silico modelling provided a plausible explanation of the pronounced reduction in the oral bioavailability of trospium when administered with food. The simulation results support the decreased dissolution in viscous medium, and the reduced drug permeability in the fed state as the predominant mechanisms for the food effect on trospium absorption. Copyright
PB  - Wiley-Blackwell, Hoboken
T2  - Biopharmaceutics & Drug Disposition
T1  - Improvement of trospium-specific absorption models for fasted and fed states in humans
VL  - 35
IS  - 9
SP  - 553
EP  - 558
DO  - 10.1002/bdd.1911
ER  - 

@article{
author = "Cvijić, Sandra and Langguth, Peter",
year = "2014",
abstract = "The purpose of this study was to mechanistically interpret the oral absorption pattern of trospium in fasted and fed states by means of gastrointestinal simulation technology. A drug absorption model was built on the basis of experimental data. According to the generated model, low permeability across the intestinal epithelium, delayed gastric emptying time and a prolonged residence time in the small intestine are the key factors governing trospium absorption in the fasted state. Furthermore, in silico modelling provided a plausible explanation of the pronounced reduction in the oral bioavailability of trospium when administered with food. The simulation results support the decreased dissolution in viscous medium, and the reduced drug permeability in the fed state as the predominant mechanisms for the food effect on trospium absorption. Copyright",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Biopharmaceutics & Drug Disposition",
title = "Improvement of trospium-specific absorption models for fasted and fed states in humans",
volume = "35",
number = "9",
pages = "553-558",
doi = "10.1002/bdd.1911"
}

Cvijić, S.,& Langguth, P.. (2014). Improvement of trospium-specific absorption models for fasted and fed states in humans. in Biopharmaceutics & Drug Disposition
Wiley-Blackwell, Hoboken., 35(9), 553-558.
https://doi.org/10.1002/bdd.1911

Cvijić S, Langguth P. Improvement of trospium-specific absorption models for fasted and fed states in humans. in Biopharmaceutics & Drug Disposition. 2014;35(9):553-558.
doi:10.1002/bdd.1911 .

Cvijić, Sandra, Langguth, Peter, "Improvement of trospium-specific absorption models for fasted and fed states in humans" in Biopharmaceutics & Drug Disposition, 35, no. 9 (2014):553-558,
https://doi.org/10.1002/bdd.1911 . .

TY  - JOUR
AU  - Kovacević, Ivan
AU  - Parojčić, Jelena
AU  - Tubić-Grozdanis, Marija
AU  - Langguth, Peter
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1239
AB  - The Biopharmaceutics Classification System (BCS) is based on the mechanistic assumptions that the rate and extent of oral drug absorption are governed by drug solubility, intestinal permeability, and dissolution rate from the dosage form administered. One of the goals of BCS is to identify classes of drugs for which bioequivalence may be established based solely on the in vitro dissolution data, i.e., which would be eligible for biowaiver. On the basis of BCS, currently, the biowaiver concept is adopted and recommended for immediate release of drug products containing highly soluble and highly permeable compounds (BCS class 1 drugs). Dissolution testing properties are proposed to be more stringent: very rapid dissolution is demanded when generic drug application is submitted with the exemption of in vivo bioequivalence study. In the present paper, Gastrointestinal Simulation Technology has been applied in order to evaluate the potential for different in vitro drug dissolution kinetics to influence dosage forms in vivo behavior and the relevance of "very rapid dissolution" criteria to be met (i.e., more than 85% of dose dissolved in 15 min).
PB  - Springer, New York
T2  - AAPS Journal
T1  - An Investigation into the Importance of "Very Rapid Dissolution" Criteria for Drug Bioequivalence Demonstration using Gastrointestinal Simulation Technology
VL  - 11
IS  - 2
SP  - 381
EP  - 384
DO  - 10.1208/s12248-009-9114-3
ER  - 

@article{
author = "Kovacević, Ivan and Parojčić, Jelena and Tubić-Grozdanis, Marija and Langguth, Peter",
year = "2009",
abstract = "The Biopharmaceutics Classification System (BCS) is based on the mechanistic assumptions that the rate and extent of oral drug absorption are governed by drug solubility, intestinal permeability, and dissolution rate from the dosage form administered. One of the goals of BCS is to identify classes of drugs for which bioequivalence may be established based solely on the in vitro dissolution data, i.e., which would be eligible for biowaiver. On the basis of BCS, currently, the biowaiver concept is adopted and recommended for immediate release of drug products containing highly soluble and highly permeable compounds (BCS class 1 drugs). Dissolution testing properties are proposed to be more stringent: very rapid dissolution is demanded when generic drug application is submitted with the exemption of in vivo bioequivalence study. In the present paper, Gastrointestinal Simulation Technology has been applied in order to evaluate the potential for different in vitro drug dissolution kinetics to influence dosage forms in vivo behavior and the relevance of "very rapid dissolution" criteria to be met (i.e., more than 85% of dose dissolved in 15 min).",
publisher = "Springer, New York",
journal = "AAPS Journal",
title = "An Investigation into the Importance of "Very Rapid Dissolution" Criteria for Drug Bioequivalence Demonstration using Gastrointestinal Simulation Technology",
volume = "11",
number = "2",
pages = "381-384",
doi = "10.1208/s12248-009-9114-3"
}

Kovacević, I., Parojčić, J., Tubić-Grozdanis, M.,& Langguth, P.. (2009). An Investigation into the Importance of "Very Rapid Dissolution" Criteria for Drug Bioequivalence Demonstration using Gastrointestinal Simulation Technology. in AAPS Journal
Springer, New York., 11(2), 381-384.
https://doi.org/10.1208/s12248-009-9114-3

Kovacević I, Parojčić J, Tubić-Grozdanis M, Langguth P. An Investigation into the Importance of "Very Rapid Dissolution" Criteria for Drug Bioequivalence Demonstration using Gastrointestinal Simulation Technology. in AAPS Journal. 2009;11(2):381-384.
doi:10.1208/s12248-009-9114-3 .

Kovacević, Ivan, Parojčić, Jelena, Tubić-Grozdanis, Marija, Langguth, Peter, "An Investigation into the Importance of "Very Rapid Dissolution" Criteria for Drug Bioequivalence Demonstration using Gastrointestinal Simulation Technology" in AAPS Journal, 11, no. 2 (2009):381-384,
https://doi.org/10.1208/s12248-009-9114-3 . .

TY  - JOUR
AU  - Kovacević, Ivan
AU  - Parojčić, Jelena
AU  - Homšek, Irena
AU  - Tubić-Grozdanis, Marija
AU  - Langguth, Peter
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1252
AB  - The aim of the present study was to use gastrointestinal simulation technology and in vitro-in vivo correlation (IVIVC) as tools to investigate a possible extension of biowaiver criteria to BCS class II drugs using carbamazepine (CBZ) as a candidate compound. Gastrointestinal simulation based on the advanced compartmental absorption and transit model implemented in GastroPlus was used. Actual in vitro and in vivo data generated in CBZ bioequivalence studies were used for correlation purposes. The simulated plasma profile, based on the CBZ physicochemical and pharmacokinetic properties, was almost identical with that observed in vivo. Parameter sensitivity analysis (PSA) indicated that the percent of drug absorbed is relatively insensitive to the variation of the input parameters. Additionally, plasma concentration-time profiles were simulated based on dissolution profiles observed under the different experimental conditions. Regardless of the differences observed in vitro, the predicted pharmacokinetic profiles were similar in the extent of drug exposure (AUC) while there were certain differences in parameters defining the drug absorption rate (C-max, t(max)). High level A IVIVC was established for the pooled data set (r = 0.9624), indicating that 1% SLS may be considered as the universal biorelevant dissolution medium for both the IR and CR CBZ tablets. The proposed methodology involving gastrointestinal simulation technology and IVIVC suggests that there is a rationale for considering CBZ biowaiver extension and introduction of the wider dissolution specifications for CBZ immediate release tablets.
PB  - Amer Chemical Soc, Washington
T2  - Molecular Pharmaceutics
T1  - Justification of Biowaiver for Carbamazepine, a Low Soluble High Permeable Compound, in Solid Dosage Forms Based on IVIVC and Gastrointestinal Simulation
VL  - 6
IS  - 1
SP  - 40
EP  - 47
DO  - 10.1021/mp800128y
ER  - 

@article{
author = "Kovacević, Ivan and Parojčić, Jelena and Homšek, Irena and Tubić-Grozdanis, Marija and Langguth, Peter",
year = "2009",
abstract = "The aim of the present study was to use gastrointestinal simulation technology and in vitro-in vivo correlation (IVIVC) as tools to investigate a possible extension of biowaiver criteria to BCS class II drugs using carbamazepine (CBZ) as a candidate compound. Gastrointestinal simulation based on the advanced compartmental absorption and transit model implemented in GastroPlus was used. Actual in vitro and in vivo data generated in CBZ bioequivalence studies were used for correlation purposes. The simulated plasma profile, based on the CBZ physicochemical and pharmacokinetic properties, was almost identical with that observed in vivo. Parameter sensitivity analysis (PSA) indicated that the percent of drug absorbed is relatively insensitive to the variation of the input parameters. Additionally, plasma concentration-time profiles were simulated based on dissolution profiles observed under the different experimental conditions. Regardless of the differences observed in vitro, the predicted pharmacokinetic profiles were similar in the extent of drug exposure (AUC) while there were certain differences in parameters defining the drug absorption rate (C-max, t(max)). High level A IVIVC was established for the pooled data set (r = 0.9624), indicating that 1% SLS may be considered as the universal biorelevant dissolution medium for both the IR and CR CBZ tablets. The proposed methodology involving gastrointestinal simulation technology and IVIVC suggests that there is a rationale for considering CBZ biowaiver extension and introduction of the wider dissolution specifications for CBZ immediate release tablets.",
publisher = "Amer Chemical Soc, Washington",
journal = "Molecular Pharmaceutics",
title = "Justification of Biowaiver for Carbamazepine, a Low Soluble High Permeable Compound, in Solid Dosage Forms Based on IVIVC and Gastrointestinal Simulation",
volume = "6",
number = "1",
pages = "40-47",
doi = "10.1021/mp800128y"
}

Kovacević, I., Parojčić, J., Homšek, I., Tubić-Grozdanis, M.,& Langguth, P.. (2009). Justification of Biowaiver for Carbamazepine, a Low Soluble High Permeable Compound, in Solid Dosage Forms Based on IVIVC and Gastrointestinal Simulation. in Molecular Pharmaceutics
Amer Chemical Soc, Washington., 6(1), 40-47.
https://doi.org/10.1021/mp800128y

Kovacević I, Parojčić J, Homšek I, Tubić-Grozdanis M, Langguth P. Justification of Biowaiver for Carbamazepine, a Low Soluble High Permeable Compound, in Solid Dosage Forms Based on IVIVC and Gastrointestinal Simulation. in Molecular Pharmaceutics. 2009;6(1):40-47.
doi:10.1021/mp800128y .

Kovacević, Ivan, Parojčić, Jelena, Homšek, Irena, Tubić-Grozdanis, Marija, Langguth, Peter, "Justification of Biowaiver for Carbamazepine, a Low Soluble High Permeable Compound, in Solid Dosage Forms Based on IVIVC and Gastrointestinal Simulation" in Molecular Pharmaceutics, 6, no. 1 (2009):40-47,
https://doi.org/10.1021/mp800128y . .

TY  - CONF
AU  - Kovacević, Ivan
AU  - Parojčić, Jelena
AU  - Tubić-Grozdanis, Marija
AU  - Langguth, Peter
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1194
PB  - Taylor & Francis Inc, Philadelphia
C3  - Drug Metabolism Reviews
T1  - Physiologically Based In Silico Prediction of Intestinal Drug Absorption Used as a Tool to Justify the Waiver of In Vivo Bioequivalence Studies
VL  - 41
SP  - 59
EP  - 59
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1194
ER  - 

@conference{
author = "Kovacević, Ivan and Parojčić, Jelena and Tubić-Grozdanis, Marija and Langguth, Peter",
year = "2009",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Drug Metabolism Reviews",
title = "Physiologically Based In Silico Prediction of Intestinal Drug Absorption Used as a Tool to Justify the Waiver of In Vivo Bioequivalence Studies",
volume = "41",
pages = "59-59",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1194"
}

Kovacević, I., Parojčić, J., Tubić-Grozdanis, M.,& Langguth, P.. (2009). Physiologically Based In Silico Prediction of Intestinal Drug Absorption Used as a Tool to Justify the Waiver of In Vivo Bioequivalence Studies. in Drug Metabolism Reviews
Taylor & Francis Inc, Philadelphia., 41, 59-59.
https://hdl.handle.net/21.15107/rcub_farfar_1194

Kovacević I, Parojčić J, Tubić-Grozdanis M, Langguth P. Physiologically Based In Silico Prediction of Intestinal Drug Absorption Used as a Tool to Justify the Waiver of In Vivo Bioequivalence Studies. in Drug Metabolism Reviews. 2009;41:59-59.
https://hdl.handle.net/21.15107/rcub_farfar_1194 .

Kovacević, Ivan, Parojčić, Jelena, Tubić-Grozdanis, Marija, Langguth, Peter, "Physiologically Based In Silico Prediction of Intestinal Drug Absorption Used as a Tool to Justify the Waiver of In Vivo Bioequivalence Studies" in Drug Metabolism Reviews, 41 (2009):59-59,
https://hdl.handle.net/21.15107/rcub_farfar_1194 .