Products Under Development
Several pharmaceutical companies are developing pulmonary insulin delivery systems. These products are in various stages of development and fall into two main groups: solution and dry powder formulations ( Table 1 ), which are delivered through different patented inhaler systems.[9,10,11,12] Each of the formulations are based on regular human insulin.
The most widely studied insulin product for pulmonary delivery is Exubera, a rapid-acting insulin in powder form.[12] This particular product contains insulin powder (particle size of <7.5 μm) combined with dry powder carrier. This dry powder carrier is generally amorphous and enhances stability of insulin during storage. The powder preparation is packed into blisters with different dosages, and a specialized inhaler is used to deliver the drug to the lungs. This specialized inhaler generates a pulse of compressed air, thus deagglomerating the dry powder insulin into a cloud and delivering it from the blister into a reservoir, from which it is to be inhaled. The standing cloud of aerosol eliminates highvelocity impact of insulin on the throat and upper airway; the device encourages a slow, deep inspiration for maximum deep-lung delivery. The product has been studied extensively in patients with type 1 and type 2 diabetes mellitus. The bioavailability of this product is approximately 10%, compared with regular human insulin administered by subcutaneous injection.[13]
The AERx Insulin Diabetes Management System (AERx iDMS) delivers a liquid form of human insulin.[14] The delivery device includes a unique breath-guidance system that allows patients to breathe optimally and reproducibly. The drug is delivered to the lung only when the breathing is correct. This feature is not available in any other aerosolized insulin products being developed. This device also features a datadownloading system, facilitating the review of dose administration data and breathing technique. This system uses strips with liquid insulin, which makes dosage adjustment possible to the nearest unit, as is done with insulin injections. The system has been studied in patients with type 1 and type 2 diabetes mellitus. The bioavailability of insulin following the use of AERx iDMS was 1317%. The electronic monitoring features also provide clinicians with valuable information about patient dosing regimens and compliance.[14]
Other pulmonary insulin delivery systems, including ProMaxx, AIR, Spiros, and Technosphere, are also under investigation. ProMaxx uses a proprietary technology to prepare 15-μm microspheres. These microspheres can release drug immediately or provide sustained drug release over minutes or months. The product shows excellent in vitro stability and reproducible size.
AIR uses a proprietary technology to prepare large porous microparticles.[15,16,17] The density of the particles is less than 0.4 g/cm3, which allows particles over 5 μm in geometric diameter to deposit into the deep-lung region. In a comparison with small, nonporous insulin particles, these large porous particles had a 24 times longer duration of action (4 hours versus 96 hours). Alkermes is currently conducting the Phase II clinical trial, and Eli Lilly is providing the financial support for product development.
Technosphere Insulin System is an ordered lattice array of spherical particles and 18% insulin formulated as a crystalline dry powder.[18] The aerodynamic diameter of the particles is 0.45.8 μm. A commercially available asthma inhaler was used to deliver Technosphere insulin during the proof-of-concept study. The bioavailability of Technosphere insulin is 1526%. In another study using radiolabeled particles, the Technosphere insulin was equally distributed across the whole area of both lungs.[19]
The newest pulmonary insulin product under development is Aerodose insulin. The product is designed to deliver a proprietary liquid insulin formulation. A breath-activated inhaler incorporates a cartridge that allows patients to adjust the dosage based on their insulin requirements. The product has been studied in a small group of patients with type 2 diabetes mellitus.[20] This study showed that the relative bioavailability of inhaled Aerodose insulin was approximately 21%. Despite promising results, Aerogen Corporation failed to secure a financial partner and halted development of the product in January 2003.
Am J Health Syst Pharm. 2005;62(13):1359-1364. © 2005 American Society of Health-System Pharmacists
Cite this: Inhaled Insulin for Diabetes Mellitus - Medscape - Jul 01, 2005.
