TY  - JOUR
AU  - Medarević, Đorđe 
AU  - Cvijić, Sandra
AU  - Dobričić, Vladimir
AU  - Mitrić, Miodrag
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
PY  - 2018
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0928098718303919
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7861
AB  - This study aimed to improve dissolution rate of valsartan in an acidic environment and consequently its oral bioavailability by solid dispersion formulation. Valsartan was selected as a model drug due to its low oral bioavailability (~23%) caused by poor solubility of this drug in the low pH region of gastrointestinal tract (GIT) and presence of absorption window in the upper part of GIT. Solid dispersions were prepared by solvent evaporation method with Eudragit® E100, Soluplus® or polyvinylpyrrolidone K25 (PVP K25) in drug:polymer weight ratios of 1:1, 1:2, 1:4 and 1:6 and further subjected to solid-state characterization and in vitro drug dissolution testing in 0.1 M HCl. The expected drug plasma concentration vs. time profiles after oral administration of the selected solid dispersion formulations were predicted using physiologically-based in silico modeling. Fast and complete dissolution of valsartan, with >80% of dissolved drug within the first 10 min of testing, was observed only from solid dispersions prepared with Eudragit® E100 in drug:polymer ratios of 1:2, 1:4 and 1:6. In all other samples, valsartan dissolution was slow and incomplete. Solid-state characterization showed amorphous nature of both pure drug and solid dispersion samples, as well as favourable intermolecular interactions between valsartan and polymers over interactions between drug molecules. The constructed in silico model predicted >40% of increase in valsartan bioavailability, Cmax and AUC values from selected solid dispersion formulations compared to conventional solid oral dosage form such as IR capsules. Based on the results of the in vitro-in silico study, formulation of solid dispersions of valsartan with Eudragit® E100 polymer can be considered as a promising approach for improving valsartan bioavailability. © 2018 Elsevier B.V.
T2  - European Journal of Pharmaceutical Sciences
T1  - Assessing the potential of solid dispersions to improve dissolution rate and bioavailability of valsartan: In vitro-in silico approach
VL  - 124
SP  - 188
EP  - 198
DO  - 10.1016/j.ejps.2018.08.026
ER  - 

@article{
author = "Medarević, Đorđe  and Cvijić, Sandra and Dobričić, Vladimir and Mitrić, Miodrag and Đuriš, Jelena and Ibrić, Svetlana",
year = "2018",
abstract = "This study aimed to improve dissolution rate of valsartan in an acidic environment and consequently its oral bioavailability by solid dispersion formulation. Valsartan was selected as a model drug due to its low oral bioavailability (~23%) caused by poor solubility of this drug in the low pH region of gastrointestinal tract (GIT) and presence of absorption window in the upper part of GIT. Solid dispersions were prepared by solvent evaporation method with Eudragit® E100, Soluplus® or polyvinylpyrrolidone K25 (PVP K25) in drug:polymer weight ratios of 1:1, 1:2, 1:4 and 1:6 and further subjected to solid-state characterization and in vitro drug dissolution testing in 0.1 M HCl. The expected drug plasma concentration vs. time profiles after oral administration of the selected solid dispersion formulations were predicted using physiologically-based in silico modeling. Fast and complete dissolution of valsartan, with >80% of dissolved drug within the first 10 min of testing, was observed only from solid dispersions prepared with Eudragit® E100 in drug:polymer ratios of 1:2, 1:4 and 1:6. In all other samples, valsartan dissolution was slow and incomplete. Solid-state characterization showed amorphous nature of both pure drug and solid dispersion samples, as well as favourable intermolecular interactions between valsartan and polymers over interactions between drug molecules. The constructed in silico model predicted >40% of increase in valsartan bioavailability, Cmax and AUC values from selected solid dispersion formulations compared to conventional solid oral dosage form such as IR capsules. Based on the results of the in vitro-in silico study, formulation of solid dispersions of valsartan with Eudragit® E100 polymer can be considered as a promising approach for improving valsartan bioavailability. © 2018 Elsevier B.V.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Assessing the potential of solid dispersions to improve dissolution rate and bioavailability of valsartan: In vitro-in silico approach",
volume = "124",
pages = "188-198",
doi = "10.1016/j.ejps.2018.08.026"
}

Medarević, Đ., Cvijić, S., Dobričić, V., Mitrić, M., Đuriš, J.,& Ibrić, S.. (2018). Assessing the potential of solid dispersions to improve dissolution rate and bioavailability of valsartan: In vitro-in silico approach. in European Journal of Pharmaceutical Sciences, 124, 188-198.
https://doi.org/10.1016/j.ejps.2018.08.026

Medarević Đ, Cvijić S, Dobričić V, Mitrić M, Đuriš J, Ibrić S. Assessing the potential of solid dispersions to improve dissolution rate and bioavailability of valsartan: In vitro-in silico approach. in European Journal of Pharmaceutical Sciences. 2018;124:188-198.
doi:10.1016/j.ejps.2018.08.026 .

Medarević, Đorđe , Cvijić, Sandra, Dobričić, Vladimir, Mitrić, Miodrag, Đuriš, Jelena, Ibrić, Svetlana, "Assessing the potential of solid dispersions to improve dissolution rate and bioavailability of valsartan: In vitro-in silico approach" in European Journal of Pharmaceutical Sciences, 124 (2018):188-198,
https://doi.org/10.1016/j.ejps.2018.08.026 . .