The aim of this case study was to develop a drug-specific absorption model for levothyroxine (LT4) using mechanistic gastrointestinal simulation technology (GIST) implemented in the GastroPlus (TM) software package. The required input parameters were determined experimentally, in silico predicted and/or taken from the literature. The simulated plasma profile was similar and in a good agreement with the data observed in the in vivo bioequivalence study, indicating that the GIST model gave an accurate prediction of LT4 oral absorption. Additionally, plasma concentrationtime profiles were simulated based on a set of experimental and virtual in vitro dissolution data in order to estimate the influence of different in vitro drug dissolution kinetics on the simulated plasma profiles and to identify biorelevant dissolution specification for LT4 immediate-release (IR) tablets. A set of experimental and virtual in vitro data was also used for correlation purposes. In vitroin vivo correlation mo...del based on the convolution approach was applied in order to assess the relationship between the in vitro and in vivo data. The obtained results suggest that dissolution specification of more than 85% LT4 dissolved in 60 min might be considered as biorelevant dissolution specification criteria for LT4 IR tablets. Copyright
Keywords:
levothyroxine / gastrointestinal simulation / dissolution / in vitro-in vivo correlation
Source:
Biopharmaceutics & Drug Disposition, 2012, 33, 3, 146-159
TY - JOUR
AU - Kocić, Ivana
AU - Homšek, Irena
AU - Dacević, Mirjana
AU - Cvijić, Sandra
AU - Parojčić, Jelena
AU - Vučićević, Katarina
AU - Prostran, Milica
AU - Miljković, Branislava
PY - 2012
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1704
AB - The aim of this case study was to develop a drug-specific absorption model for levothyroxine (LT4) using mechanistic gastrointestinal simulation technology (GIST) implemented in the GastroPlus (TM) software package. The required input parameters were determined experimentally, in silico predicted and/or taken from the literature. The simulated plasma profile was similar and in a good agreement with the data observed in the in vivo bioequivalence study, indicating that the GIST model gave an accurate prediction of LT4 oral absorption. Additionally, plasma concentrationtime profiles were simulated based on a set of experimental and virtual in vitro dissolution data in order to estimate the influence of different in vitro drug dissolution kinetics on the simulated plasma profiles and to identify biorelevant dissolution specification for LT4 immediate-release (IR) tablets. A set of experimental and virtual in vitro data was also used for correlation purposes. In vitroin vivo correlation model based on the convolution approach was applied in order to assess the relationship between the in vitro and in vivo data. The obtained results suggest that dissolution specification of more than 85% LT4 dissolved in 60 min might be considered as biorelevant dissolution specification criteria for LT4 IR tablets. Copyright
PB - Wiley-Blackwell, Malden
T2 - Biopharmaceutics & Drug Disposition
T1 - A case study on the in silico absorption simulations of levothyroxine sodium immediate-release tablets
VL - 33
IS - 3
SP - 146
EP - 159
DO - 10.1002/bdd.1780
ER -
@article{
author = "Kocić, Ivana and Homšek, Irena and Dacević, Mirjana and Cvijić, Sandra and Parojčić, Jelena and Vučićević, Katarina and Prostran, Milica and Miljković, Branislava",
year = "2012",
abstract = "The aim of this case study was to develop a drug-specific absorption model for levothyroxine (LT4) using mechanistic gastrointestinal simulation technology (GIST) implemented in the GastroPlus (TM) software package. The required input parameters were determined experimentally, in silico predicted and/or taken from the literature. The simulated plasma profile was similar and in a good agreement with the data observed in the in vivo bioequivalence study, indicating that the GIST model gave an accurate prediction of LT4 oral absorption. Additionally, plasma concentrationtime profiles were simulated based on a set of experimental and virtual in vitro dissolution data in order to estimate the influence of different in vitro drug dissolution kinetics on the simulated plasma profiles and to identify biorelevant dissolution specification for LT4 immediate-release (IR) tablets. A set of experimental and virtual in vitro data was also used for correlation purposes. In vitroin vivo correlation model based on the convolution approach was applied in order to assess the relationship between the in vitro and in vivo data. The obtained results suggest that dissolution specification of more than 85% LT4 dissolved in 60 min might be considered as biorelevant dissolution specification criteria for LT4 IR tablets. Copyright",
publisher = "Wiley-Blackwell, Malden",
journal = "Biopharmaceutics & Drug Disposition",
title = "A case study on the in silico absorption simulations of levothyroxine sodium immediate-release tablets",
volume = "33",
number = "3",
pages = "146-159",
doi = "10.1002/bdd.1780"
}
Kocić, I., Homšek, I., Dacević, M., Cvijić, S., Parojčić, J., Vučićević, K., Prostran, M.,& Miljković, B.. (2012). A case study on the in silico absorption simulations of levothyroxine sodium immediate-release tablets. in Biopharmaceutics & Drug Disposition
Wiley-Blackwell, Malden., 33(3), 146-159.
https://doi.org/10.1002/bdd.1780
Kocić I, Homšek I, Dacević M, Cvijić S, Parojčić J, Vučićević K, Prostran M, Miljković B. A case study on the in silico absorption simulations of levothyroxine sodium immediate-release tablets. in Biopharmaceutics & Drug Disposition. 2012;33(3):146-159.
doi:10.1002/bdd.1780 .
Kocić, Ivana, Homšek, Irena, Dacević, Mirjana, Cvijić, Sandra, Parojčić, Jelena, Vučićević, Katarina, Prostran, Milica, Miljković, Branislava, "A case study on the in silico absorption simulations of levothyroxine sodium immediate-release tablets" in Biopharmaceutics & Drug Disposition, 33, no. 3 (2012):146-159,
https://doi.org/10.1002/bdd.1780 . .
