Formulation and evaluation of insulin dry powder for inhalation.
OBJECTIVE
Dry powder formulation of insulin for pulmonary administration was prepared to obtain increased drug deposition in the alveolar absorptive region. The deposition was studied by investigating the dispersion and deaggregation of insulin from the carrier lactose using an Andersen cascade impactor and twin stage impinger. The subsequent absorption following the deposition was studied by in vivo method.


METHODS
Insulin in solution with absorption promoters was lyophilized. The powder was incorporated with lactose of different grades and their combinations as carriers to deliver using an inhaler device. Solid-state characteristics of the carrier as well as the drug powder were assessed by particle size and distribution measurement. The flow properties such as moisture content, powder density, angle of repose, and carr's compressibility index of the powder mixture were determined. The aerosol behavior of the powder was studied by dispersion using rotahaler(c) connected to a twin-stage impinger (TSI) and an eight-stage Andersen cascade impactor (ACI) operating at different flow rates of 30-90 l/min. The in vivo performance was studied by deliverance to the respiratory tract of guinea pigs. The intratracheal bioavailability with respective to intravenous route was calculated by measuring the blood glucose reduction.


RESULTS
The coarser particles of lactose in fractions of carrier containing a wide particle size distribution impacted in the preseperator of cascade impactor, and only the particle less than 10 microm size entered stage 0-stage 7. Formulation containing 1:1 mixture of Respitose ML006 (62%<50 microm) and Respitose ML003 (37.8%<50 microm) as carrier imparts well deaggregation of insulin, and higher deposition leads to 52.3% of fine particle fraction at 60 Lit/min and in vivo bioavailability of 82%.


CONCLUSIONS
Insulin formulations containing 1:1 mixture of Respitose ML006 and Respitose ML003 as carrier can impart deeper deposition of drug particles and cause higher bioavailability. This suggests that carrier used in the formulation influenced the amount of insulin deposition in the alveolar region of the lung. Hence, it was concluded that the availability of insulin for systemic absorption depends on the particle size of the drug as well as the carrier lactose.
Mahesh Kumar
T
T
Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, M S University of Baroda, Gujarat, India.
Misra
Ambikanandan
A
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007785:Lactose / Q000737:chemistry*; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders
D000336:Aerosols; D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011208:Powders; D007785:Lactose