An Investigation into the Influence of Experimental Conditions on In Vitro Drug Release from Immediate-Release Tablets of Levothyroxine Sodium and Its Relation to Oral Bioavailability
Abstract
The aim of this study was to investigate the influence of experimental conditions on levothyroxine sodium release from two immediate-release tablet formulations which narrowly passed the standard requirements for bioequivalence studies. The in vivo study was conducted as randomised, single-dose, two-way cross-over pharmacokinetic study in 24 healthy subjects. The in vitro study was performed using various dissolution media, and obtained dissolution profiles were compared using the similarity factor value. Drug solubility in different media was also determined. The in vivo results showed narrowly passing bioequivalence. Considering that levothyroxine sodium is classified as Class III drug according to the Biopharmaceutics Classification System, drug bioavailability will be less sensitive to the variation in its dissolution characteristics and it can be assumed that the differences observed in vitro in some of investigated media probably do not have significant influence on the absorptio...n process, as long as rapid and complete dissolution exists. The study results indicate that the current regulatory criteria for the value of similarity factor in comparative dissolution testing, as well as request for very rapid dissolution (more than 85% of drug dissolved in 15 min), are very restricted for immediate-release dosage forms containing highly soluble drug substance and need further investigation. The obtained results also add to the existing debate on the appropriateness of the current bioequivalence standards for levothyroxine sodium products.
Keywords:
bioequivalence / dissolution / immediate release / levothyroxine sodium / solubilitySource:
AAPS PharmSciTech, 2011, 12, 3, 938-948Publisher:
- Springer, New York
Funding / projects:
DOI: 10.1208/s12249-011-9660-8
ISSN: 1530-9932
PubMed: 21748540
WoS: 000294492900016
Scopus: 2-s2.0-80052568377
Collections
Institution/Community
PharmacyTY - JOUR AU - Kocić, Ivana AU - Homšek, Irena AU - Dacević, Mirjana AU - Parojčić, Jelena AU - Miljković, Branislava PY - 2011 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1476 AB - The aim of this study was to investigate the influence of experimental conditions on levothyroxine sodium release from two immediate-release tablet formulations which narrowly passed the standard requirements for bioequivalence studies. The in vivo study was conducted as randomised, single-dose, two-way cross-over pharmacokinetic study in 24 healthy subjects. The in vitro study was performed using various dissolution media, and obtained dissolution profiles were compared using the similarity factor value. Drug solubility in different media was also determined. The in vivo results showed narrowly passing bioequivalence. Considering that levothyroxine sodium is classified as Class III drug according to the Biopharmaceutics Classification System, drug bioavailability will be less sensitive to the variation in its dissolution characteristics and it can be assumed that the differences observed in vitro in some of investigated media probably do not have significant influence on the absorption process, as long as rapid and complete dissolution exists. The study results indicate that the current regulatory criteria for the value of similarity factor in comparative dissolution testing, as well as request for very rapid dissolution (more than 85% of drug dissolved in 15 min), are very restricted for immediate-release dosage forms containing highly soluble drug substance and need further investigation. The obtained results also add to the existing debate on the appropriateness of the current bioequivalence standards for levothyroxine sodium products. PB - Springer, New York T2 - AAPS PharmSciTech T1 - An Investigation into the Influence of Experimental Conditions on In Vitro Drug Release from Immediate-Release Tablets of Levothyroxine Sodium and Its Relation to Oral Bioavailability VL - 12 IS - 3 SP - 938 EP - 948 DO - 10.1208/s12249-011-9660-8 ER -
@article{ author = "Kocić, Ivana and Homšek, Irena and Dacević, Mirjana and Parojčić, Jelena and Miljković, Branislava", year = "2011", abstract = "The aim of this study was to investigate the influence of experimental conditions on levothyroxine sodium release from two immediate-release tablet formulations which narrowly passed the standard requirements for bioequivalence studies. The in vivo study was conducted as randomised, single-dose, two-way cross-over pharmacokinetic study in 24 healthy subjects. The in vitro study was performed using various dissolution media, and obtained dissolution profiles were compared using the similarity factor value. Drug solubility in different media was also determined. The in vivo results showed narrowly passing bioequivalence. Considering that levothyroxine sodium is classified as Class III drug according to the Biopharmaceutics Classification System, drug bioavailability will be less sensitive to the variation in its dissolution characteristics and it can be assumed that the differences observed in vitro in some of investigated media probably do not have significant influence on the absorption process, as long as rapid and complete dissolution exists. The study results indicate that the current regulatory criteria for the value of similarity factor in comparative dissolution testing, as well as request for very rapid dissolution (more than 85% of drug dissolved in 15 min), are very restricted for immediate-release dosage forms containing highly soluble drug substance and need further investigation. The obtained results also add to the existing debate on the appropriateness of the current bioequivalence standards for levothyroxine sodium products.", publisher = "Springer, New York", journal = "AAPS PharmSciTech", title = "An Investigation into the Influence of Experimental Conditions on In Vitro Drug Release from Immediate-Release Tablets of Levothyroxine Sodium and Its Relation to Oral Bioavailability", volume = "12", number = "3", pages = "938-948", doi = "10.1208/s12249-011-9660-8" }
Kocić, I., Homšek, I., Dacević, M., Parojčić, J.,& Miljković, B.. (2011). An Investigation into the Influence of Experimental Conditions on In Vitro Drug Release from Immediate-Release Tablets of Levothyroxine Sodium and Its Relation to Oral Bioavailability. in AAPS PharmSciTech Springer, New York., 12(3), 938-948. https://doi.org/10.1208/s12249-011-9660-8
Kocić I, Homšek I, Dacević M, Parojčić J, Miljković B. An Investigation into the Influence of Experimental Conditions on In Vitro Drug Release from Immediate-Release Tablets of Levothyroxine Sodium and Its Relation to Oral Bioavailability. in AAPS PharmSciTech. 2011;12(3):938-948. doi:10.1208/s12249-011-9660-8 .
Kocić, Ivana, Homšek, Irena, Dacević, Mirjana, Parojčić, Jelena, Miljković, Branislava, "An Investigation into the Influence of Experimental Conditions on In Vitro Drug Release from Immediate-Release Tablets of Levothyroxine Sodium and Its Relation to Oral Bioavailability" in AAPS PharmSciTech, 12, no. 3 (2011):938-948, https://doi.org/10.1208/s12249-011-9660-8 . .