Artificial Lipid Membrane Permeability Method for Predicting Intestinal Drug Transport: Probing the Determining Step in the Oral Absorption of Sulfadiazine; Influence of the Formation of Binary and Ternary Complexes with Cyclodextrins.

We propose an in vitro permeability assay by using a modified lipid membrane to predict the in vivo intestinal passive permeability of drugs. Two conditions were tested, one with a gradient pH (pH 5.5 donor/pH 7.

Binding of sulfamethazine to β-cyclodextrin and methyl-β-cyclodextrin.

β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) complexes with sulfamethazine (SMT) were prepared and characterized by different experimental techniques, and the effects of βCD and MβCD on drug solubility were assessed via phase-solubility analysis. The phase-solubility diagram for the drug showed an increase in water solubility, with the following affinity constants calculated: 40.4±0.

Complexation of sulfonamides with beta-cyclodextrin studied by experimental and theoretical methods.

The complex formation between three structurally related sulfonamides (sulfadiazine (SDZ), sulfamerazine (SMR), and sulfamethazine (SMT)) and beta-cyclodextrin (beta-CD) was studied, by exploring its structure affinity relationship. In all the cases, 1:1 stoichiometries were determined with different relative affinities found by phase solubility (SDZ:beta-CD > SMR:beta-CD > SMT:beta-CD) and nuclear magnetic resonance (NMR) (SMT:beta-CD > SMR:beta-CD > SDZ:beta-CD) studies. The spatial configurations determined by NMR were in agreement with those obtained by molecular modeling, showing that SDZ included its aniline ring into beta-CD, while SMR and SMT included the substituted pyrimidine ring.