DEEP LUNG AEROSOL DEVICES

518 Vincent Street, Spring City, PA 19475 USA PN: +1 (610) 948-7100, FX: +1 (610) 948-2018

Internet: amici-inc.com/drugdelivery.htm, e-mail: mbono@amici-inc.com

Product Brief

Swirler® Aerosol System Generally speaking, people tend to associate nebulizers with asthma patients where a drug, in aerosol form, is used to treat a patient’s breathing difficulties. In their minds, nebulizers are all the same, just different shapes, sizes and colors from different manufacturers. In most cases this is true. The exception is for ‘Systemic Aerosol Drug Delivery’ where the aerosol droplets must be smaller than 1.1 micron in size to negotiate the airways for deposition in the alveoli. The ‘Systemic Aerosol Drug Delivery’ market is presently estimated to be $25 Billion per year. At the moment, the only approved deep lung aerosol drug is Pfizer’s ‘Exubera’ which is an insulin for diabetic’s. Many companies are attempting to compete for their piece of the ‘Systemic Aerosol Therapeutic’ business with poorly performing aerosol devices. The following information shows the ideal deep lung aerosol generating devices to be the ‘Micro Cirrus’ and the ‘Swirler’. Their major difference is that the Swirler generates sub-micronic droplets three times faster. In mechanical terms, our lungs can be described as the site of gas exchange. Oxygen and deep lung aerosolized medications are extracted from the air we inhale, at the alveolar level, and infused into the bloodstream to be distributed throughout the body. The anatomy of the human respiratory system is very much like a hollowed out inverted deciduous tree with the leaves resembling the alveoli. Balls of different sizes, dropped into this tree trunk example, will stop traveling at the limit of their diameters. To deposit in the leaves, balls must be small enough to pass through the last bifurcation. In order for particles or droplets to deposit in the alveoli (deep lung) they must be smaller than 1.1 micrometers in size. The Swirler Patents resulted from the need for “Alveolar Targeted Medications” are used for “Nuclear Medicine Lung Diagnostics” as well as “Systemic Aerosol Drug Delivery”. Jet Nebulizers were selected for their:

• Proven sub-micronic aerosol capabilities • Operational familiarity • Manufacturing and testing simplicity • Disposability and Cost

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Typical Jet Nebulizers operate by directing an airflow (gas) through an Air Inlet that passes through the first Orifice causing liquid from the reservoir, to siphon between two walls (Liquid feed channel) and come in contact with the air stream. The combined air and liquid then travel through a second orifice for sizing and directed to a Baffle causing the stream to break up into droplets. Smaller droplets exit through the Outlet and larger droplets fall back into the Reservoir for re-nebulization. Droplet sizes are determined mainly by the stream and orifice dimensions. Simplistic examples of this concept are:

To defy the ‘droplet size to rate-of-production compromise’, one obvious solution is to increase the number of airstreams. This is achieved, in the Swirler Nebulizer, by swirling the airflow that not only siphons the liquid, but also creates a shearing affect on the liquid, resulting in a thin circular output resembling continuously connected streams. See the shearing example below to the left and the actual cross sectional Swirler design drawing to the right.

The performance comparison chart to the right shows the Swirler is:

Outlet

Air inlet

Baffle

Liquid feed channel

Liquid reservoir

Orifice

Swirler

Ideal for Alveolar Drug Delivery

Nebulizer Median ObscurationRaindrop TM 1.14 µm 23.86%

UltraVent TM 1.02 µm 18.97%

Micro Cirrus TM 0.64 µm 8.66%

Swirler ® 0.62 µm 21.04%

Orifice

Liquid feed channel

Outlet

Air inlet

Baffle

Liquid reservoir

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• Superior in Alveolar Deposition (.62 microns) • Has small loss of drug in the Airway • High Rate of Delivery (21.04% Obscuration)

The lung images below compare the same patient under the same conditions except for the nebulizer choice. The 200K on the image indicates the number of data points (number of scintillation events) in the whole field of view. The Swirler image shows a much greater amount of drug is deposited in the deep lung (alveoli). The Brand X image shows less drug deposited in the alveoli and the remaining in the mouth, airways, esophagus, stomach, duodenum etc. with less deep lung deposition. The Swirler Radioaerosol System, Model 7030 with the narrower spectrum, has been serving Diagnostic Nuclear Medicine globally since 1997 through AMICI, Inc. Many other patented Swirler devices are presently available for Systemic Aerosol (deep lung) Drug Delivery. All Swirler products are 100% quality tested to be leakage free prior to shipping. Certifications: GMP, CE, ISO9001 and ISO14385. Intellectual Property : USA =5603314, 5611332, 6230703, 5630409, D295,797 & D433,125 EU = EP-UK0830164 AUS = 713481 Publications for Diagnostic Imaging and Systemic Therapeutic Aerosols:

• Evaluation and Design of Nebulizers for Nuclear Medicine Diagnostics.. • Deep Lung Delivery of Water-Insoluble Drug NanochrystalsTM via the AMICI SwirlerTM Nebulizer System. • Hyperpolarized 3He MR Imaging of Pulmonary Function. • 99MTC-ENS vs 99MTC-DTPA as Aerosol Lung Scintiscanning Agents.