Barbara Haeberlin

Cyclodextrins — Useful excipients for oral peptide administration?

Abstract Cyclodextrins have been investigated for their potential use as excipients for the oral delivery of peptides. A modified calcitonin and the somatostatin analog octapeptide octreotide (Sandostatin ® ) were chosen as model drugs. Both the potential of cyclodextrins for metabolic and physicochemical stabilization, as well as their use as absorption enhancers were evaluated in vitro using the Caco-2 cell monolayer model and in in situ absorption experiments with rats. Physical mixtures of the peptides with α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxypropyl-β-cyclodextrin and dimethyl-β-cyclodextrin were used throughout the experiments. The use of β-cyclodextrin and hydroxypropyl-β-cyclodextrin resulted in an increased chemical and enzymatic stability of the peptides. β-Cyclodextrin, γ-cyclodextrin and hydroxypropyl-β-cyclodextrin also showed absorption enhancing properties in the in vitro system as well as in the in situ study. No beneficial effects were observed for α-cyclodextrin. An enhanced permeation of the paracellular marker PEG-4000 across the cell monolayers in the presence of distinct cyclodextrins indicated an impairment of the tight junctional integrity as one reason for improved peptide absorption. The results suggest that distinct cyclodextrins have protective and absorption enhancing effects on peptides by preparing simple physical mixtures of the two components. However, the extent of protection and absorption enhancement seems to depend strongly on the nature of the peptide used as well as the chosen cyclodextrin.