The effects of cyclodextrins on drug absorption. I. In vitro observations

A two-phase transfer system, water with organic solvent, was used to investigate the effect of cyclodextrins on transport of dissolved lipophilic drugs from the aqueous to the organic layer. Four model drugs, diazepam, medazepam, n-butyl-p-aminobenzoate and n-pentyl-p-aminobenzoate were used. Stability constants of different cyclodextrin complexes were determined by a phase solubility technique or by a spectral displacement technique. It was found that the first-order transport rate constants of the drugs were hardly affected by complexation with β-cyclodextrin. This phenomenon could be explained by displacement of the drug from the cyclodextrin complex by organic solvent near the interface. This process results in a unique system which has a low concentration of free drug in the bulk of the aqueous layer, whereas near the interface a relatively high concentration of free drug exists. It could be demonstrated that the properties of the organic solvent also influenced the transport rate of complexed dru