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. 2017 Feb;30(1):20-41.
doi: 10.1089/jamp.2016.1297. Epub 2016 Oct 17.

The History of Therapeutic Aerosols: A Chronological Review

Free PMC article

The History of Therapeutic Aerosols: A Chronological Review

Stephen W Stein et al. J Aerosol Med Pulm Drug Deliv. .
Free PMC article


In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems. The innovative inhalers and drugs discovered by the pharmaceutical aerosol industry, particularly since 1956, have improved the quality of life of literally hundreds of millions of people. Yet, the delivery of therapeutic aerosols has a surprisingly rich history dating back more than 3500 years to ancient Egypt. The delivery of atropine and related compounds has been a crucial inhalation therapy throughout this period and the delivery of associated structural analogs remains an important therapy today. Over the centuries, discoveries from many cultures have advanced the delivery of therapeutic aerosols. For thousands of years, therapeutic aerosols were prepared by the patient or a physician with direct oversight of the patient using custom-made delivery systems. However, starting with the Industrial Revolution, advancements in manufacturing resulted in the bulk production of therapeutic aerosol delivery systems produced by people completely disconnected from contact with the patient. This trend continued and accelerated in the 20th century with the mass commercialization of modern pharmaceutical inhaler products. In this article, we will provide a summary of therapeutic aerosol delivery from ancient times to the present along with a look to the future. We hope that you will find this chronological summary intriguing and informative.

Keywords: atropine; dry powder inhaler; inhaler; metered dose inhaler; nebulizer; therapeutic aerosol.

Conflict of interest statement

Author Disclosure Statement No competing financial interests exist.


<b>FIG. 1.</b>
FIG. 1.
A schematic representation of the oldest known reference (c. 1554 BC) of therapeutic aerosol delivery in which smoke of henbane plants was inhaled through the stalk of a reed.
<b>FIG. 2.</b>
FIG. 2.
The oldest known drawing of a therapeutic inhaler device developed in 1654 by the English physician Christopher Bennet. Image courtesy of Mark Sanders.
<b>FIG. 3.</b>
FIG. 3.
A drawing (a) and photo (b) of the Mudge Inhaler.(17) As the patient inhaled through the flexible mouthpiece, air was drawn through the three holes on the handle and the air was bubbled through the medicated liquid before exiting the mouthpiece. The right side of the drawing shows the valve configuration, which utilized a small cork that moved and allowed the exhaled breath of the patient to exit the tankard. Images courtesy of Mark Sanders.
<b>FIG. 4.</b>
FIG. 4.
Page's asthma cigarettes containing stramonium, tea leaves, chestnut leaves, and gum benzoin. Image courtesy of Mark Sanders.
<b>FIG. 5.</b>
FIG. 5.
The pulverisateur developed by Jean Sales-Girons in 1858. Image courtesy of Mark Sanders.
<b>FIG. 6.</b>
FIG. 6.
A drawing of the first DPI invented by Ira Warren in 1852.
<b>FIG. 7.</b>
FIG. 7.
A picture (a) and schematic drawing (b) of Abbott's Aerohalor. Images courtesy of Mark Sanders.
<b>FIG. 8.</b>
FIG. 8.
A drawing of the first MDI, Medihaler Iso, which consisted of a plastic-coated glass vial crimped to a 50 mcl metering valve, the formulation, and the plastic mouthpiece adapter.
<b>FIG. 9.</b>
FIG. 9.
A photograph of the first commercial breath actuated MDI, the Autohaler, along with a transparent demonstrator device.
<b>FIG. 10.</b>
FIG. 10.
Schematic drawings of two early DPI devices. Images courtesy of Andy Clark.
<b>FIG. 11.</b>
FIG. 11.
The number of U.S. patent families containing the phrase “metered dose inhaler or dry powder inhaler” in the title, claims, or abstract plotted against the year of the priority filing.
<b>FIG. 12.</b>
FIG. 12.
The number of published HFA MDI patents for the 10 companies with the largest patent portfolios (with the percentage of all HFA MDI patents). Adapted from Rogueda et al.(64)
<b>FIG. 13.</b>
FIG. 13.
The Diskus DPI as provided to the patient (a) and after disassembly to show the coil dosing strip containing the 60 individual foil blisters [bottom right portion of the image (b)].
<b>FIG. 14.</b>
FIG. 14.
Powders harvested from commercial DPIs. (a) Spray-dried recombinant human insulin from Exubera. (b) Pulmospheres™ from Tobi® Podhaler™. (c) An ordered blend of lactose and salbutamol harvested from Asmasal Clickhaler.
<b>FIG. 15.</b>
FIG. 15.
A picture of a Respimat inhaler.

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