OBJECTIVE: Gastric delivery has been utilized for oral delivery of peptides. However, target site of the delivery is uncontrollable due to the housekeeping wave. In addition, dilution and spreading of peptides and permeation enhancers in the stomach may limit the oral peptide bioavailability. In this study, we developed mucoadhesive tablets containing SNAC and a GIP/GLP1 dual agonist peptide (LY) to localize the peptide delivery and minimize the dilution effect in the stomach.
METHODS: The mucoadhesive tablets were prepared as bilayer or trilayer tablets with sodium alginate on one or both sides of the formulation layer (LY/SNAC). Mucoadhesion tests were conducted using a rotating cylinder mounted with isolated rat and minipig gastric tissues, and in vivo in monkeys. Oral bioavailability of the peptide was determined in monkeys via oral administration of the mucoadhesive tablets.
RESULTS: The mucoadhesive tablets dissolved > 80% within 15 min at pH 6.8. The trilayer SNAC tablets adhered to the isolated gastric tissues. Following oral administration to monkeys, 10/10 mucoadhesive tablets were retained in the monkey stomach 10-20 min post-dose compared to 1/3 SNAC control tablets. Oral bioavailability of LY peptide was of similar magnitude as that achieved with the SNAC control tablet. In vivo dissolution of the mucoadhesive tablets was slower than the control tablets leading to lower SNAC concentration at the tablet site in the monkey stomach.
CONCLUSION: These data suggest that the mucoadhesive tablets improved gastric retention but did not increase oral bioavailability of the LY peptide following gastric delivery in monkeys.
