Supervisors info:
Ειρήνη Παντερή, Καθηγήτρια Τμήμα Φαρμακευτικής ΕΚΠΑ,
Φώτης Τσόπελας, Επίκουρος Καθηγητής Τμήμα Φαρμακευτικής ΕΚΠΑ,
Άννα Τσαντίλη- Κακουλίδου, Ομότιμη Καθηγήτρια Τμήμα Φαρμακευτικής ΕΚΠΑ
Summary:
The aim of this diploma thesis was the investigation of the mechanism of elution of
pharmaceutical active substances, by the method of liquid chromatography, in presence
of micelles, while using the non-ionic surfactant Tween 80. Then, based on the
experimentally retention rate of the 84 drugs which analyzed, was correlated with some
pharmacokinetic properties, which are useful for the development and evaluation of
new drugs.
To determine the retention rate, a reverse phase column was used as the static phase in
a water bath at 370C and for the stationary phase and the buffer drug, with pH 7.4 and
the eluent was a buffer, with pH 7,4, combined with the non-ionic surfactant Tween 80.
For simulation reasons of gastrointestinal tract which appears a pH graduation and
given that acidic drugs show reduced ionization and increased lipophilicity at acidic pH
values, 30 of the drugs studied in the context of this diploma thesis (mainly acidic and
ampholytic) were also investigated at pH 5,5 of the same buffer.
Correlations were performed between the resulting retention rate (logkwTween80) with the
dividend coefficient and the allocation coefficient, both generating successful
correlation results. Then, additional correlations were made between the logkwTween80
with the retention rates that had been obtained in similar experiments using different
surfactants, but also with the chromatographic coefficients of immobilized IAM. All
correlations, except for IAM, were satisfactory.
Finally, the correlation with pharmacokinetic properties was studied. Indicatively, a
moderate correlation was made with cell permeability through intestinal epithelial
Caco-2 cell lines and not satisfactory correlation was made with the permeability
through artificial membrane lines, PAMPA. At the same time, predictive models were
applied in order to correlate protein binding and gastrointestinal absorption of oral
drugs. The results for the simulation of the gastrointestinal absorption were quite
satisfactory, while the models for the protein binding prediction models were
moderately satisfactory.
Keywords:
Biomimetic Chromatography, Micellar Chromatography, Liquid Chromatography, Tween 80, Lipophilia, Pharmacokinetics, Cellular Permeability, Gastrointestinal Absorption, Protein Binding