ENHANCED INTESTINAL-ABSORPTION OF AN RGD PEPTIDE FROM WATER-IN-OIL MICROEMULSIONS OF DIFFERENT COMPOSITION AND PARTICLE-SIZE

The fibrinogen receptor antagonist SK and F 106760 is a water-soluble tetrapeptide (M(r) 634) with very low oil/water partitioning and membr ane permeability. Thus, the intraduodenal bioavailability of this pept ide in the rat from a saline formulation was found to be less than 1%. Upon formulation, however, in w/o microemulsions of different composi tion and particle size, the intraduodenal bioavailability of SK and F 106760 was increased up to 29% depending on the microemulsion composit ion. There was no apparent correlation between the particle size of mi croemulsions (mean droplet diameter of 0.010-1.0 mu m) and enhanced ab sorption. None of the investigated microemulsions induced gross change s in gastrointestinal mucosa at a dosing volume of 3.3 ml/kg. Lipids c ontaining medium-chain fatty acids play a major role on the observed a bsorption enhancement. These findings further support the use of micro emulsion formulations for oral drug/peptide delivery, provided however , that development issues with these systems are properly addressed.