Optimization of nasal delivery of insulin

Polireddy Dondeti, University of Rhode Island


Insulin was loaded into drug carriers such as ammonium glycyrrhizinate (AG), polyacrylic acid (PAA), cross-linked polyacrylic acid (CPAA), polyethylene oxide (PEO) and chitosan (CHTN) by two methods: supercritical fluid processing and freeze-drying. Both the loading methods resulted in powders that differed significantly in particle morphology, size distributions, release profiles and thermograms. When evaluated in diabetic rabbits, the powders loaded with insulin by carbon dioxide infusion resulted in significantly higher absorption in terms of pharmacokinetic and pharmacodynamic parameters as compared to those powders prepared by freeze-drying. There was a three-fold increase in the nasal bioavailability when AG was used as a drug carrier (9.8% vs 2.9%). A bioavailability of 8.1% was obtained for CO2 infused PAA powder as compared to much lower absorption seen with freeze-dried formulation. Similarly, a two fold increase in bioavailability was observed when CO$\sb2$ infused CPAA powder formulation was compared with the freeze-dried powder (3.6% vs 1.8%). Nasal administration of PEO and CHTN powders loaded with insulin by CO$\sb2$ infusion resulted in low bioavailabilities of 1.55% and 1.18% respectively. Among the powders evaluated, polyacrylic acid and ammonium glycyrrhizinate and carbon dioxide infusion as drug-loading method seem to offer good potential for development of a nasal powder dosage form for insulin.^ Insulin spray solutions containing two bioadhesive polymers microcrystalline cellulose (MCC) and Plastoid L50 alone or in combination with enhancers such as sodium taurocholate (ST), ammonium glycyrrhizinate (AG) or glycyrrhetinic acid (GA) at 1% w/v level, were characterized in-vitro for globule size distributions and rheological properties. When evaluated in-vivo, higher absorption of insulin was attained with sprays containing combination of polymers and enhancers. Among the sprays evaluated, MCC+ST provided the maximum nasal bioavailability of insulin (8.4%) followed by MCC+AG (7.8%). Also the presence of preservatives in formulation has significantly increased the absorption of insulin (1.9% to 6.3%). Thus the nasal spray containing bioadhesive polymer and reduced levels of enhancer seems to be a viable alternative to the injection of insulin. ^

Subject Area

Chemistry, Biochemistry|Chemistry, Pharmaceutical|Health Sciences, Pharmacy

Recommended Citation

Polireddy Dondeti, "Optimization of nasal delivery of insulin" (1994). Dissertations and Master's Theses (Campus Access). Paper AAI9526558.