Human insulin plus sodium glycocholate in a nasal spray formulation: improved bioavailability and effectiveness in normal subjects.
Intranasal insulin is effective in raising serum insulin (IRI) levels and lowering blood glucose levels in normal subjects and in diabetics, but its bioavailability is low. Our aim was to improve the bioavailability of intranasally administered insulin in normal subjects as a prerequisite to extended clinical trials. Solutions of regular porcine and human insulin, 40 U/ml, with sodium glycocholate 1 % w/v as a surfactant, administered in drops (0.9 U/Kg b.w.), were equally effective in terms of bioavailability and of hypoglycaemic activity. Spray solutions (0.5 U/Kg b.w.) of human insulin, 100 U/ml, were more effective than drops, and of the two surfactants employed, sodium glycocholate 4 % w/v was significantly more effective than 9-lauryl-ether and more effective than other formulations used here or described by other authors. Although being subject to further improvement, the formulation of human insulin 100 U/ml plus sodium glycocholate 4 % w/v delivered as a spray solution described in this study appears to be worthy of clinical trials in diabetic patients.
Pontiroli
A E
AE
Istituto Scientifico San Raffaele, Cattedra di Clinica Medica, Universitá di Milano, Italy.
Alberetto
M
M
Pajetta
E
E
Calderara
A
A
Pozza
G
G
D000281:Administration, Intranasal; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D004311:Double-Blind Method; D006000:Glycocholic Acid; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D001786:Blood Glucose; D007328:Insulin; D006000:Glycocholic Acid