Κατεύθυνση Βιομηχανική Φαρμακευτική
Library of the School of Science

2024-05-02

2024

Karagianni Spyridoula

Associate Professor Maria Vertzoni
Department of Pharmacy, National and Kapodistrian University of Athens, Greece
(Academic Supervisor, Member of the Advisory committee)
Professor Christos Reppas
Department of Pharmacy, National and Kapodistrian University of Athens, Greece
(Member of the Advisory committee)
Associate Professor Aris Dokoumetzidis
PhD, Department of Pharmacy, National and Kapodistrian University of Athens, Greece
(Member of the Advisory committee

Developing an in vitro methodology for the assessment of drug presence in the upper gastrointestinal lumen when the dose is administered to healthy adults after a high-calorie, high-fat meal

English

Developing an in vitro methodology for the assessment of drug presence in the upper gastrointestinal lumen when the dose is administered to healthy adults after a high-calorie, high-fat meal

Purpose: To develop a biorelevant gastrointestinal transfer system (BioGITfed) for studying the drug
transfer process from the antrum through the upper small intestine 30 min after the ingestion of a
high-calorie, high-fat meal to healthy adults and to evaluate the usefulness of BioGITfed in predicting
concentrations in the antrum and in the upper small intestine after disintegration of immediate
release dosage forms in the antrum of healthy adults based on luminal data.
Methods: The methodology was designed based on existing key parameter values for
gastrointestinal transfer kinetics estimated from luminal data collected after the administration of
the high calorie high fat meal (Dietrich et al 2024). Its implementation in vitro was based on a fourcompartment setup. Reproducibility of the transfer process was evaluated under conditions where
paracetamol solution or danazol suspension were present in gastric compartment. The usefulness of
BioGITfed in predicting luminal concentrations was evaluated using danazol suspension and
itraconazole amorphous solid dispersion pellets from Sporanox® capsules. The level of simulation
and the pH of the medium simulating the gastric contents and the rotational speed of the paddles
were optimized. The transfer process as well as concentrations of danazol and itraconazole
measured in the gastric and the duodenal compartment of BioGITfed were compared with data
previously collected in the antrum and in the upper small intestine, respectively, of healthy adults,
after administration of identical preparations/dosage forms 30 min after the ingestion of a highcalorie, high-fat meal.
Results: The transfer process was performed according to theoretically expected values. The transfer
process and danazol apparent concentration in the aqueous phase of gastric contents and in the
micellar phase of duodenal contents of BioGITfed were in line with luminal data in humans when
Level III FeSSGF-V3 was used in the gastric compartment. Itraconazole apparent concentration in the
colloidal phase of the gastric and duodenal contents of BioGITfed overestimated the apparent
concentration in the colloidal phase of the gastric contents and the contents of the upper small
intestine collected for healthy adults. Itraconazole apparent concentration in the aqueous phase of
the gastric contents and in the micellar phase of the duodenal contents of BioGITfed were in line
with the apparent concentration in the colloidal phase of the contents collected from the antrum
and the upper small intestine of healthy adults when Level III FeSSGF-V3 (pH 4) was used in
BioGITfed gastric compartment.
Conclusions: BioGITfed system could be useful for the evaluation of the impact of gastrointestinal
transfer on concentrations, after oral administration of solid disintegrating dose units. However, the
in vitro evaluation of luminal product performance in the fed state requires consideration of the
sample treatment procedures in order to be useful

Science

fed state, in vitro methods, biorelevant media, drug dissolution, gastrointestinal absorption, BioGIT, drug transfer process, high-calorie, high-fat meal

No

0

Yes

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https://pergamos.lib.uoa.gr/uoa/dl/object/3397932