NASAL INSULIN DELIVERY IN RABBITS USING SOYBEAN-DERIVED STERYLGLUCOSIDE AND STEROL MIXTURES AS NOVEL ENHANCERS IN SUSPENSION DOSAGE FORMS

The effect of a soybean-derived sterol mixture (SS) and a steryl gluco side mixture (SG) as enhancers of the nasal absorption of insulin in r abbits was investigated. SS consists of beta-sitosterol (Sit), campest erol (Camp), stigmasterol (Stig) and brassicasterol (Bras), and SG is a mixture of their monoglucosides. For each component of SS tested for efficacy in promoting the systemic absorption of nasally administered insulin, the following order was observed: Sit greater than or equal to Camp > Stig. This finding was in agreement with the order of the en hancers' lipophilicity. In the case of SG, the effect of beta-sitoster ol beta-D-glucoside (Sit-G) was significantly greater than that of sc. The pharmacological bioavailability was 6.7% for SG and 11.3% for Sit -G in the suspension dosage forms. SG showed a greater degree of enhan cement of insulin permeation through the nasal mucosa than SS. To eluc idate the contribution of SG to the enhanced absorption, insulin perme ation through an artificial membrane and the nasal mucosa was investig ated in vitro, and the results were compared with those for SS. The fi ndings suggest that sc and SS have some effect on nasal mucosa lipids.