Buccal delivery of fluorescein isothiocyanate-dextran 4400 and the peptide drug buserelin with glycodeoxycholate as an absorption enhancer in pigs

Delivery of drugs via the buccal mucosa is an alternative for the low oral absorption and inconvenient parenteral administration of hydrophilic macromolecular drugs. Due to the low permeability of the buccal epithelium the use of absorption enhancers is a prerequisite. In this study, buccal delivery of fluorescein isothiocyanate-labelled dextran 4400 (FD4) and the peptide drug buserelin was investigated in vivo, in pigs. The delivery device consisted of an application chamber with a solution of FD4 or buserelin, and was attached to the buccal mucosa for 4 h using an adhesive patch. A randomized cross-over study including intravenous administration and buccal delivery without and with 10 mM sodium glycodeoxycholate (GDC) as absorption enhancer was performed in pigs. After buccal administration steady-state plasma levels were rapidly achieved. Go-administration of 10 mM GDC increased the absolute bioavailability from 1.8 +/- 0.5% to 12.7 +/- 2.0% for FD4, and from 1.0 +/- 0.3% to 5.3 +/- 1.1% for buserelin. From the present studies it is concluded that buccal administration is a suitable route of delivery for macromolecules and hydrophilic compounds such as peptide drugs.