Inhaled insulin is better absorbed when administered as a dry powder compared to solution in the presence or absence of alkylglycosides.
OBJECTIVE
This study was performed to investigate the safety of alkylglycosides administered via the respiratory route and to compare the pulmonary absorption profiles of insulin administered as dry powder inhaler and inhaler solution.


METHODS
The safety of a series of alkylglycosides with varying alkyl chain lengths was studied by measuring the enzymatic activities in the bronchoalveolar lavage (BAL) fluid of rat lungs. Pulmonary formulations of insulin plus octylmaltoside were administered either as solution or lyophilized dry powder to anesthetized rats, and absorption of insulin was assessed by measuring plasma insulin and glucose levels. The physical characterization of the dry powder formulation was performed using scanning electron microscope (SEM) and Fourier transform infrared spectrophotometer (FTIR).


RESULTS
The BAL analysis showed that there was a gradual increase in the amount of lung injury markers released with the increase in the hydrophobic chain length of alkylglycosides. The pulmonary administration of lyophilized dry powder of insulin plus octylmaltoside or its solution counterpart showed that the bioavailability of powder formulation was about 2-fold higher than that of the formulation administered as solution. The SEM studies showed a subtle difference in the surface morphologies of formulation particles after lyophilization. FTIR data showed minor interactions between the peptide and excipients upon lyophilization.


CONCLUSIONS
Of the alkylglycosides tested, octylmaltoside was least toxic in releasing lung injury markers. Octylmaltoside-based dry powder insulin formulations were more efficacious in enhancing pulmonary insulin absorption and reducing plasma glucose levels compared with the formulations administered as a solution.
Hussain
Alamdar
A
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter, Amarillo, Texas 79106, USA.
Majumder
Quamrul H
QH
Ahsan
Fakhrul
F
D000280:Administration, Inhalation; D000818:Animals; D019540:Area Under Curve; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D006027:Glycosides / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D009330:Nebulizers and Vaporizers; D019999:Pharmaceutical Solutions; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared
D005079:Excipients; D006027:Glycosides; D007004:Hypoglycemic Agents; D007328:Insulin; D019999:Pharmaceutical Solutions; D011208:Powders