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

• Autor(a) principal: de Castro, Baltazar
• Data de Publicação: 2001
• Outros Autores: Gameiro, Paula, Guimarães, Carla, Lima, José L.F.C, Reis, Salette
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10284/8324
• topic: Partition coefficients; Bile salts; Solubility; Mixed micelles; β-blockers

The objective of this study was to develop non-invasive spectroscopic methods to quantify the partition coefficients of two β-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 (Kp) at 25.0±0.1°C 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 Kp. Drug partition was controlled by the: (i) drug properties, with the more soluble drug in water (atenolol) exhibiting smaller values of Kp, 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 Kp for the β-blockers, and with glycine conjugation of the bile acid increasing the values of Kp for the β-blockers. Addition of lecithin to bile salt micelles decreases the values of Kp of the β-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.