1998 AAPS Annual Meeting

 

2234

ENHANCED NASAL DELIVERY OF I NSULIN FROM AN OIL-IN-WATER EMULSION VEHICLE. Ranjana Mitra*, Alex Chu, Isabelle Pezron and Ashim K. Mitra. Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri, Kansas City, MO 64110.

 

Purpose.

The objective of this research project is to improve nasal absorption of a hydrophilic peptide Insulin. It has been hypothesized that by incorporating this peptide in the aqueous continuous phase of an oil in water emulsion, nasal transport can be enhanced.

Methods.

Various compositions of o/w and w/o emulsions have been prepared by mixing soy bean oil with Tween 80 + Span 80 [ emulsifier] and by incorporating aqueous phase of peptide, containing 0.04 mg/ml [ 1 U/ml] Insulin . The emulsion was perfused continuously through the rat nasal cavity using an in situ perfusion technique. Percent (%) remaining of blood glucose was monitored by Chemstrip method. Simultaneous appearance of the drug in plasma was monitored using a radio immunoassay procedure.

Results.

Formulation

Pharmacokinetic

Results (n = 3-5)

Pharmacodynamic

Results (n = 3-5)

 

CSS

uIU/ml

(AUC)0-180 min

Glucose redu at t=60 (%)

(AAC)0-120 min

Insulin in saline

110

22600

± 8400

12

2700

± 1000

Ins.in 50/50,o/w

446

64900

± 13500

39

4520

± 200

Ins.in 95/5,o/w

480

49560

± 8500

61

6220

± 800

Ins in 20/80,w/o

25

1400

± 1000

0

0

Conclusions.

When insulin is incorporated in w/o emulsion absorption is found to be completely inhibited probably due to the very low permeability of insulin across the continuous oil phase. The o/w emulsion (95 % water and 5 % oil) appeared to cause maximum enhancement of insulin nasal absorption and may be used as a liquid vehicle for the optimum nasal delivery of this bioactive peptide. Presence of lipid probably enhances transcytotic transport of the peptide.

Acknowledgment.

Hoechst-Marion-Roussel.