Partition coefficients of beta-blockers in bile salt/lecithin micelles as a tool to assess the role of mixed micelles in gastrointestinal absorption

• Type: Article in International Scientific Journal
• Date: 2001

Authors

de Castro, B (Author) FCUP; Gameiro, P (Author) FCUP; Guimaraes, C (Author) Other; Lima, JLFC (Author) FFUP; Reis, S (Author) FFUP

Journal

Title: Biophysical Chemistry

Vol. 90

Pages: 31-43

ISSN: 0301-4622

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 25 Citations

Scopus - 29 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-000-W39

DOI: 10.1016/s0301-4622(01)00126-0

Abstract (EN): The objective of this study was to develop non-invasive spectroscopic methods to quantify the partition coefficients of two beta -blockers, atenolol and nadolol, in aqueous solutions of bile salt micelles and to assess the effect of lecithin on the partition coefficients of amphiphilic drugs in mixed bile salt/lecithin micelles, which were used as a simple model for the naturally occurring mixed micelles in the gastrointestinal tract. The partition coefficients (K-p) at 25.0 +/- 0.1 degreesC and at 0.1 M NaCl ionic strength were determined by spectrofluorimetry and by derivative spectrophotometry, by fitting equations that relate molar extinction coefficients and relative fluorescence intensities to the partition constant K-p. Drug partition was controlled by the: (i) drug properties, with the more soluble drug in water (atenolol) exhibiting smaller values of K-p, and with both drugs interacting more extensively in the protonated form; and by (ii) the bile salt monomers, with the dihydroxylic salts producing larger values of K-p for the beta -blockers, and with glycine conjugation of the bile acid increasing the values of K-p for the beta -blockers. Addition of lecithin to bile salt micelles decreases the values of K-p of the beta -blockers. Mixed micelles incorporate hydrophobic compounds due to their large size and the fluidity of their core, but amphiphilic drugs, for which the interactions are predominantly polar/electrostatic, are poorly incorporated in mixed micelles of bile salts/lecithin.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13