Influence of deposition and spray pattern of nasal powders on insulin bioavailability.
The influence of the deposition pattern and spray characteristics of nasal powder formulations on the insulin bioavailability was investigated in rabbits. The formulations were prepared by freeze drying a dispersion containing a physical mixture of drum dried waxy maize starch (DDWM)/Carbopol 974P (90/10, w/w) or a spray-dried mixture of Amioca starch/Carbopol 974P (25/75, w/w). The deposition in the nasal cavity of rabbits and in a silicone human nose model after actuation of three nasal delivery devices (Monopowder, Pfeiffer and experimental system) was compared and related to the insulin bioavailability. Posterior deposition of the powder formulation in the nasal cavity lowered the insulin bioavailability. To study the spray pattern, the shape and cross-section of the emitted powder cloud were analysed. It was concluded that the powder bulk density of the formulation influenced the spray pattern. Consequently, powders of different bulk density were prepared by changing the solid fraction of the freeze dried dispersion and by changing the freezing rate during freeze drying. After nasal delivery of these powder formulations no influence of the powder bulk density and of the spray pattern on the insulin bioavailability was observed.
Pringels
E
E
Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.
Callens
C
C
Vervaet
C
C
Dumont
F
F
Slegers
G
G
Foreman
P
P
Remon
J P
JP
D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D005612:Freeze Drying; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061389:Insulin, Regular, Pork; D008953:Models, Anatomic; D009079:Mucociliary Clearance; D009296:Nasal Cavity / Q000378:metabolism*; D009330:Nebulizers and Vaporizers; D011208:Powders; D011817:Rabbits
D000336:Aerosols; D007004:Hypoglycemic Agents; D007328:Insulin; D061389:Insulin, Regular, Pork; D011208:Powders; C000006:insulin, neutral