Self-emulsifying drug delivery systems (SEDDS): In vivo-proof of concept for oral delivery of insulin glargine

In spite of recent progress made in the field of peptide and protein delivery, oral administration of insulin and similar drugs remains a challenge. In this study, lipophilicity of insulin glargine (IG) was successfully increased via hydrophobic ion pairing (HIP) with sodium octadecyl sulfate to enable incorporation into self-emulsifying drug delivery systems (SEDDS). Two SEDDS formulations (F1: 20% Labrasol (R) ALF, 30% polysorbate 80, 10% Croduret 50, 20% oleyl alcohol, 20% Maisine (R) CC; F2: 30% Labrasol (R) ALF, 20% polysorbate 80, 30% Kolli-phor (R) HS 15, 20% Plurol (R) oleique CC 497) were developed and loaded with the IG-HIP complex. Further ex-periments confirmed increased lipophilicity of the complex, achieving LogDSEDDS/release medium values of 2.5 (F1) and 2.4 (F2) and ensuring sufficient amounts of IG within the droplets after dilution. Toxicological assays indicated minor toxicity and no toxicity inherent to the incorporated IG-HIP complex. SEDDS formulations F1 and F2 were administered to rats via oral gavage and resulted in a bioavailability of 0.55% and 0.44%, corre-sponding to a 7.7-fold and 6.2-fold increased bioavailability, respectively. Thus, incorporation of complexed insulin glargine into SEDDS formulations provides a promising approach to facilitate its oral absorption.