"Air Passage," Feature Article, May 2003

air passage

With the right pressure and size, taking your medicine could be as easy as inhaling.

This article was prepared by staff writers in conjunction with outside contributors.

A company is developing a family of inhalation devices that can do more than treat respiratory ailments. They can deliver medication for diabetes and other conditions by spraying it to reach the bloodstream through the lungs. The company, Aradigm Corp. of Hayward, Calif., now has one of the inhalers—designed to deliver insulin—near the end of its clinical trials, well along the road toward the federal greenlight for commercial introduction.

When a layman hears "inhaler," he thinks of treatment for asthma or bronchitis. The device could be used for that, according to Aradigm's principal mechanical engineer, Rob Clark, but it can also use the lungs as the avenue to the bloodstream, where medicine can be introduced efficiently to the body.

Computer image of pressure at a key moment.

The trick, he said, is to make the spray droplets fine enough to penetrate to the lungs' tiny sacs, the alveoli, where exchanges between blood and the outside world take place. The aerosol particles must be "in the range of a few microns," he explained.

Aradigm calls the system AERx. The version in clinical trials fits the hand and accepts a disposable strip that contains 50 microliters of insulin solution sealed inside a blister of laminated plastic. The disposable strip also contains a laser-machined nozzle, an array of very fine holes that will cause the liquid to divide into a mist of micrometer-scale droplets. An electrically actuated piston drives the liquid from its reservoir through the nozzle array and into the respiratory system.

To take the medicine, the patient breathes through the device. A differential pressure transducer in the inhaler senses when the patient's breathing has reached the best condition for receiving the medication and, at that point, automatically triggers the piston. The patient can determine beforehand how much of the drug to take. Piston travel is electronically controlled to regulate the dosage.

To make sure all the insulin takes the proper route, the AERx inhaler has a clamp that bears down on the strip during delivery. The clamp channels the liquid and keeps it from escaping in the wrong direction.

"This clamp is designed to create a pressure around the periphery far in excess of the hydraulic pressure within the reservoir, ensuring that the peel seal cannot open in the clamped regions," said Eric Johansson, director of electrical engineering and project leader at Aradigm.

The product took shape as a 3-D CAD file in Pro/Engineer software from PTC of Needham, Mass. To study how the piston and clamp would perform under pressure, the 3-D model went through finite element analysis in PTC's Pro/Mechanica.

The AERx strip fits a hand-held delivery device. On actuation, a clamp reinforces the drug reservoir so the right dose will flow where it needs to go.

Physical prototypes, tested using a pressure-sensitive film, confirmed FEA results. The film, called Pressurex, is made by Fuji Photo Film Co. Ltd. of Japan and marketed by Sensor Products Inc. of East Hanover, N.J. It is a sandwich in which two sheets of polyester hold a layer of microcapsules and a layer of developer. The capsules break at different pressures to release a chemical. The developer fixes the chemical as a magenta pattern. The darker the shade, the greater the pressure.

Topaq, a companion product combining a calibrated scanner with Windows-based software, did high-resolution analysis of the film and generated a multicolor image. Sensor Products says that the computer analysis gives values accurate within 4 percent.

Aradigm is extending the AERx idea to other medical uses. For instance, it has a lockable configuration for administering opiates. The company says devices can deliver testosterone through the lungs to raise the libido in post-menopausal women, or drugs to treat hepatitis and some cancers. The company has designed a second generation of the products, smaller than those in trials, including a mechanical version that won't need a battery.