Intranasal bioavailability of insulin powder formulations: effect of permeation enhancer-to-protein ratio.
The intranasal administration of powder formulations containing insulin and the permeation enhancer sodium tauro-24,25-dihydrofusidate (STDHF) were investigated in the sheep model. Both the hypoglycemic response and the serum insulin levels increased as the mole ratio of STDHF to insulin was increased from 0 to 16.8. In vitro dissolution rates of the powders and the rapid tmax (approximately 5 min) observed after intranasal administration suggest that the absorption of insulin is not dissolution limited. The bioavailabilities (F) of the powder formulations ranged from 2.9 to 37.8%. In comparison, the F values for a solution formulation with a STDHF:insulin ratio of 8.4 administered as either drops or spray were 15.7 and 37.4%, respectively. The permeation enhancer STDHF increases mucosal permeability and reduces the average molecular weight of the insulin species.
Lee
W A
WA
California Biotechnology Inc., Mountain View 94043.
Narog
B A
BA
Patapoff
T W
TW
Wang
Y J
YJ
D000042:Absorption; D000277:Adjuvants, Pharmaceutic; D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D001682:Biological Availability; D005260:Female; D005672:Fusidic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D010539:Permeability; D011208:Powders; D011506:Proteins / Q000378:metabolism; D012996:Solutions
D000277:Adjuvants, Pharmaceutic; D000336:Aerosols; D007328:Insulin; D011208:Powders; D011506:Proteins; D012996:Solutions; D005672:Fusidic Acid; C053824:tauro-24,25-dihydrofusidate