title: Improvement of stability and absorbability of dry insulin powder for inhalation by powder-combination technique.
abstract: The effect of pulmonary absorption enhancers on the stability of active ingredients is an important factor for successful inhalation therapy as well as the effect on pharmacological activity and safety. We examined the effect of pulmonary absorption enhancers on the stability of insulin in dry powders prepared by a spray-drying technique. Although the hypoglycemic effect was greatly improved when a dry insulin powder containing citric acid (MIC SD) was administered, insulin in the MIC SD was unstable compared with the other powders examined. Bacitracin and Span 85, which are potent pulmonary absorption enhancers of insulin formulated in solutions, showed no deteriorative effect on the stability of dry insulin powder. However, they did not improve the hypoglycemic effect of insulin in dry powders. We modified the insulin dosage form with citric acid to improve the insulin stability at room temperature without loss of hypoglycemic activity. MIC Mix was formulated as a combination of insulin powder (MI') and citric acid powder (MC). MIC Mix showed hypoglycemic activity comparable to MIC SD while the insulin stability was much better than that of MIC SD at a 60 degrees C/dry condition. However, moisture lowered the insulin stability and changed the particle morphology of MIC Mix with time at a 60 degrees C/75% relative humidity condition, suggesting that a package preventing moisture absorption was necessary for the MIC Mix powder.
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Todo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
authors.forename: Kotaro
authors.initials: K
authors.lastname: Iida
authors.forename: Kazumi
authors.initials: K
authors.lastname: Danjo
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001414:Bacitracin / Q000737:chemistry; D001786:Blood Glucose / Q000032:analysis; D019343:Citric Acid / Q000737:chemistry; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D006601:Hexoses / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism; D008297:Male; D010316:Particle Size; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical; D014961:X-Ray Diffraction
chemical_list: D001786:Blood Glucose; D006601:Hexoses; D007328:Insulin; D011208:Powders; D001414:Bacitracin; D019343:Citric Acid; C005693:sorbitan trioleate