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
Само за регистроване кориснике
2014
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
Food effect / Viscosity / Disintegration / Dissolution / Poorly-permeable drugs / Absorption simulationИзвор:
European Journal of Pharmaceutical Sciences, 2014, 61, 40-53Издавач:
- Elsevier Science BV, Amsterdam
Финансирање / пројекти:
- German Academic Exchange Service (DAAD)
DOI: 10.1016/j.ejps.2014.04.008
ISSN: 0928-0987
PubMed: 24751672
WoS: 000338597800007
Scopus: 2-s2.0-84902543492
Институција/група
PharmacyTY - 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 . .