Copyright: General Practice Airways Group 2007

Primary Care Respiratory Journal (2007) 16(2): 71-81

PRIMARY CARE
RESPIRATORY
JOURNAL
REVIEW http://www.thepcrj.org

Inhalation therapy: an historical review

a,b,*
Mark Sanders
a Pharmaxis Ltd
b Creator of inhalatorium.com.

Received 6th November 2006; accepted 11th November 2006

KEYWORDS
Summary: Inhalation has been employed as a method for delivering medications
Inhalation therapy;
for more than two thousand years, and the benefits of delivering medication directly
History; to the affected site — the lungs — have been understood for more than two hundred

r o up
Asthma; years. At the beginning of the Industrial Revolution, physicians were inventing
Devices

ays G
therapies and experimenting with ideas for devices: it was a time of great creativity.

ic e A irw
However, by the end of the period the scientist and the regulated pharmaceutical

ct
industry had emerged and the role of the physician had been constrained. Few of the

ra l P r a it e d
devices invented then remain in use today, but many of the principles used are still

e n e ro h ib
embodied in modern devices. This review traces the developments produced by the

P
ig h t G t i o n
early pioneers who applied their creative thoughts to inhalation therapy, and

Copyr d uc
examines how inhaled drug delivery has progressed. The devices pictured are from

Re p ro www.inhalatorium.com, an online museum of inhalation technologies.

© 2007 General Practice Airways Group. All rights reserved.

Contents
Introduction ................................................................................................................ 72
The ‘inhaler’ ............................................................................................................... 72
Inhalation therapy in ancient times .................................................................................... 72
Inhalation therapy: the 1800s ........................................................................................... 73
The treatment of consumption ..................................................................................... 73
Inhalational anaesthesia ............................................................................................. 74
The first pressurised inhaler ........................................................................................ 74
The treatment of asthma ............................................................................................ 74
The first dry powder inhaler ........................................................................................ 75
The Nelson inhaler .................................................................................................... 75
The formal recognition of inhalation therapy .................................................................... 75
The first nebulisation devices ....................................................................................... 76
The age of advertising and the entrepreneur ......................................................................... 76
Notable inhalers and inhaled therapies from a hundred years ago ........................................... 78
The end of the entrepreneur and the age of the scientist ......................................................... 79
Modern times ............................................................................................................... 80
Conclusion .................................................................................................................. 80
References .................................................................................................................. 81

* Correspondence: 15 Friars Walk, Dunstable, Bedfordshire, LU6 3JA, UK

Tel: +44 (0)7711 995614; fax: +44 (0)1582 699732
E-mail address: [email protected]

1471-4418 © 2007 General Practice Airways Group. All rights reserved

doi:10.3132/pcrj.2007.00017

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 Copyright: General Practice Airways Group 2007
72 M. Sanders

Introduction applying medicines directly to the lung is through

the windpipe”. He advocated his own recipe of
It is tempting to think of inhalation therapy as a balsamic vapours in his book, Medical Advice to
modern approach to drug delivery, but this would the Consumptive and Asthmatic Peoples of
negate some thousands of years of history and England,3 controversially aimed at the public
literally hundreds of ingenious devices and hopeful rather than his peers.
medications. This historical review describes the
development of inhalation therapy throughout the
ages, from its first recorded use in Ancient Inhalation therapy in ancient times
Egyptian times through to the numerous different
sorts of inhalation device available today. Long before Bennet, Stern and Mudge were
describing inhalers and advocating inhalation
therapy, inhalation was being practised in many
The ‘inhaler’ parts of the world. The inhalation of the vapour of
black henbane is recorded in the ancient Egyptian
The word ‘inhaler’ was first used by the English Ebers papyrus (1,554 BC); Egyptian physicians
physician, John Mudge. In his 1778 book, A Radical threw the weed onto hot bricks, causing the
and Expeditious Cure for a recent Catarrhous alkaloid contents of the plant to vapourise so that
Cough,1 he discloses to us his invention of an the breathless patient could inhale.
inhaler adapted from a pewter tankard and the use In South and Central America, around 2,000
of opium vapour to treat cough (Figure 1). The years ago, native populations had discovered the

o up
therapeutic and recreational use of tobacco and
r
engraving in his book is not, however, the first
illustration of an inhaler. That honour goes to
ays G
Christopher Bennet in 1654 in his book Theatri

ic e A irw
ct
Tabidorum,2 with an inhaler that bore more than a

a l P r a
passing resemblance to a modern Turbohaler … (see
r it e d
e n e ro h i
Figure 2). These physicians were not just doctors
P b
ig h t G t i o n
Copyr
but they were also inventors and pioneers — there

ro d uc
was no regulated pharmaceutical industry to supply
p
Re
patient needs. Indeed, Mudge had to provide his
readers with the address of a pewterer in Fleet
Street, London who could make the Mudge inhaler.
Inhalation therapy was rationalised by Philip
Stern as early as 1764 — “the only possible way of

Figure 1 John Rudge's pewter tankard inhaler, 1778 Figure 2 Diagram of Christopher Bennet's inhaler, 1654

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 Copyright: General Practice Airways Group 2007
Inhalation therapy: an historical review 73

use a common teapot and inhale through the

spout5 — though the subsequent tea may have had
an oddly balsamic flavour! Perhaps this suggestion
was the original inspiration for the later Nelson’s
inhaler which indeed resembles a teapot …
In 1802 Gent publicised and advocated the
ancient Indian practice of inhaling the vapours
generated by burning the leaves of Datura
Stramonium, and the inhalation of various such
mixtures became very popular throughout the
1800s. Stramonium produces the anticholinergic
agent atropine.
The celebrated physician Thomas Beddoes (1760-
1808) founded the Pneumatic Institute at Clifton,
Bristol, for the treatment of disease by inhalation.
Beddoes’ work6 was the catalyst which fostered the
genius of his assistant, Humphrey Davy.
Figure 3 South American tobacco pipes c. 2000 yrs ago In 1811 François-Joseph Double, a notable
French physician, wrote Traité du Croup,7 a
similar plants. They fashioned pipes which were dissertation on croup, stating, “The inhalation of
often ornately crafted — see Figure 3. vapour, medicated with æther, opium, or cicuta,

up
In China, opium inhalation has a long history, and
o
and pediluvia rendered a little irritating by the

G r
ays
ornate metal inhalers and incense burners are addition of mustard, are also said to be

irw
associated with its practice. Accounts of asthma
A
serviceable.” It remains unclear by what means he

ct i c
predate the earliest accounts of inhalation

r a e preferred the inhalations to be administered.

l P e d
The treatment ofitconsumption
treatment, with the oldest accounts of asthma going

e n e ra ro h
back to the time of the Yellow Emperor of China in
ib
g h t G i o n P
2,600 BC. Huang-Ti, author of the oldest known
i t
Copyr o d uc period was the treatment of consumption. Asthma
A key driver for inhaler development during this
book on internal medicine, identified the use of Ma

Re p r
Huang, much later shown to contain ephedrine.
was a relatively uncommon condition. All the
Inhalation therapy was also practised in other
ancient civilisations: in India, the practice of medications depended on heat to be volatilised or
inhaling the fumes of stramonium and hemp was vapour to be aerosolised.
common, and in Ancient Greece the physician Sir Charles Scudamore in his “Cases illustrating
Hippocrates (460-377 BC) advocated the inhalation and confirming the remedial power of the
of vapours of herbs and resins boiled with vinegar inhalation of iodine and conium in tubercular
and oil which were then drawn into the lungs phthisis and various disordered states of the lungs
through a tube. Over a thousand years later, Rhazes and air-passages” published in 1834,8 describes the
(c850 AD-c923 AD), a physician in Baghdad, use of inhaling the vapour of hot water medicated
advocated the inhalation of the vapour of arsenic. with iodine and conium (hemlock). The treatment
More recently, at the end of the 12th century, was given three times a day for 15-20 minutes each
Maimonides (1135-1204 AD), the Spanish-born time using water at 120ºF. He refers back to Galen’s
physician to the Arab King Saladin, wrote the first use of arsenic fumes or orpiment. Doctors Percival
book on asthma (A Treatise on Asthma) in 1190, and Withering are mentioned for their use of
and recommended numerous treatments inhaling carbonic acid gas generated by the reaction
(including chicken soup and sexual abstention) for of chalk and vinegar and Sir Alexander Crichton is
the king’s son who was asthmatic.4 Among those credited with the practice of inhaling the vapour of
treatments was the inhalation of vapour boiling tar. Scudamore also refers to two French
generated from herbs thrown onto a fire. doctors; M.Gannel for his use of chlorine inhalation,
and Laennec for his endeavours to create an artificial
marine atmosphere by use of seaweed (after having
Inhalation therapy: the 1800s observed improvement in patients taking sea
voyages). Scudamore advocated iodine and conium
Twenty years after the appearance of Mudge’s after having experimented with inhalations of
book,1 Cavallo pointed out that, rather than using stramonium, belladonna, lobelia, ipecacuanha,
a purpose-made inhaler, the patient could simply digitalis, hydrocyanic acid and sulphuric ether.

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 Copyright: General Practice Airways Group 2007
74 M. Sanders

G r o up
A irw ays
Figure 4 The first pressurised inhaler, 1858
r a ct ic e
Figure 5 Hyde Salter's account of burning nitre

e r a l P papers, 1860

h ib it e d the liquid medication

t G e n
This was a long tubeion P ro
h
In 1834 Francis Ramadge developed an inhaler It used pressure to atomise

througho p ig
yther patient wouldpinhale
for treating consumption. 9

o d ucHe t — see Figure 4.

C
records the inhalation ofR
which
vapours,
r
e including tar, The treatment of asthma
slowly.

iodine, chlorine, hemlock, turpentine and others.

In 1860, Henry Hyde Salter published his famous
Inhalational anaesthesia text, On Asthma its Pathology and Treatment.12 He
systematically reviewed the treatment options of
On October 16th 1846, the first demonstration of the period, including inhaled therapies, and
inhaled anaesthesia took place. John Collins distinguished between depressants (ipecacuanha,
Warren performed the operation and William tobacco, tartar-emetic), stimulants (coffee,
Morton delivered the anaesthetic. The surgeon alcohol), and sedatives (tobacco, chloroform,
Henry Bigelow witnessed the operation and left an opium, Stramonium, Lobelia and Indian Hemp). The
excellent account and received much of the inhalation of the fumes of burning nitre papers was
credit. Within three weeks, on November 9, also discussed by Salter. Salter was unsure of the
Bigelow had written and presented his paper to origin of this practice, but estimates that it began
the Boston Society of Medical Improvement;10 an around 1860. He described its efficacy as being
abstract was presented at the American Academy beyond question and gave detailed accounts of four
of Arts and Sciences on November 3. The following treated cases — see Figure 5. The activity of nitre
month inhaled anaesthesia was being tried in papers is attributable to ammonia which is formed
London. Anaesthesia demanded special inhalation during the combustion process. However, vapours,
devices and there were numerous ones which in general, did not form a significant part of his
were rapidly developed. armamentarium. Salter was very negative about
the value of opium in asthma, and regarded it as
The first pressurised inhaler being more a cause than a cure, although he did
accept its role in bronchitic cough.
The first ‘powered’ or pressurised inhaler was In the USA in 1862, Charles Broadbent wrote “A
invented in France by Sales-Girons and was Medical Treatise on the Causes and Curability of
presented at the Medical Academy, Paris in 1858.11 Consumption, Laryngitis, Chronic Catarrh and

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 Copyright: General Practice Airways Group 2007
Inhalation therapy: an historical review 75

Diseases of the Air Passages — Combining the

Treatment by Inhalation by Medicated Vapours”.13
He eloquently makes the case for treatment by
vapour inhalation; “The soothing and quieting
effects of these vapors is brought immediately to
act upon the parts locally irritated and diseased,
by the gentle inhalation of the vapor from a bottle
arranged expressly for the purpose …” He justifies
delivery of the drugs directly to the lungs; “We
contend that no remedy, or combination of
remedies, however potent, whether allopathically
or homeopathically administered through the
medium of the stomach has ever nor can ever cure
a single case of asthma. For the reason that they
do not reach the seat of the disease, their
principal force is spent upon the general system,
and long before they find their way to the lungs,
their power is lost.” His reasoning was very similar
to that of Stern and Mudge many years earlier.
Broadbent describes a rich list of inhalants
familiar to him, explaining that each was made to

o up
the requirements of the individual patient;

G r
ays
“Iodine, Conium, Oxygen, Hydrogen, Nitrogen,

irw
Nitrous gas, a great variety of Gums and Balsamic

ct ic e A
Resins, Vapor of boiling Tar, Hydrocyanic Acid,

l P r a
Camphor, Ammonia, Balsam Tolu, Naphtha,
ra it e d
e n e
Chlorine, Hyoscyamus, Lactuca, Belladona,
P ro h ib
g h t G t i o n
Digitalic, Colchicum a great variety of Balsamic
i
Copyr d uc
Figure 6 The Improved Nelson inhaler, 1865
o
Herbs, Galbanum, Vapor of Vinegar, Nitre,

Re p r
Stramonium, Lobelia, Inflata, Ipecacuanha,
manufactured to this day,
Alcohol, Hydriodate of Potassa, Storax, with very few
Marshmallows, Rose Water, a great variety of modifications. A vast number, many of them quite
Emollient and Narcotic Herbs, &c.” Broadbent was ornate, have been produced under different
clearly a remarkable experimenter in terms of the names and to different designs. Maw’s catalogue16
range of substances that he employed to medicate of 1869 shows two ceramic inhalers together with
his vapours. Mudge inhalers, a Ramadge inhaler and others.

The first dry powder inhaler The formal recognition of inhalation therapy

In London in 1864, Newton patented an inhaling The 1867 edition of the British Pharmacopoeia17
apparatus for the delivery of dry powder was the first to formularise inhalation therapies. It
medications.14 He observed that the powder listed five medications;
needed to be finely pulverised and that it had to
be kept dry — principles that still apply to dry a) vapor acidi hydrocyanici
powder inhalers today. His use of potassium b) vapor chlori
chlorate as a therapy was probably unfortunate c) vapor coniae
because this is now considered to be a lung d) vapor creasoti
irritant. However, this device is probably the e) vapor iodi
earliest recorded dry powder inhaler.
For any medical therapy, listing within a major
The Nelson inhaler pharmacopoeia marks the medical acceptance of
that therapy. In this sense, inhalation therapy had
In 1865, a new invention was reported in The won its spurs and had been formally accepted as a
Lancet15 — the Improved Nelson Inhaler from the means of medical treatment. Nevertheless, most
well-known pharmacy supplier S.Maw & Sons in of the substances listed above would now be
London (see Figure 6). The Nelson inhaler is still considered unsuitable for inhalation.

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 Copyright: General Practice Airways Group 2007
76 M. Sanders

In 1867, Armand Trousseau, one of France’s most

famous doctors, published a series of lectures
which were given in Paris.18 He reviewed asthma in
detail, referring to the inhalation of stramonium,
tobacco, hyoscyamus and belladonna. He also cited
the use of opium, arsenical cigarettes, nitre
papers, and described how to prepare these
products. Trousseau refers to Dr Faure’s method of
inhaling ammonia vapour for 15 minutes (four times
a day) from a vase at a distance of about one foot,
the nostrils needing to be occluded to avoid
unpleasant effects. He observed that some patients
respond better to one medication while others
Figure 7 Siegle's steam spray inhaler, early 1860's
respond better to another.
In 1869 the German doctor Louis Waldenburg,
writing about tuberculosis,19 claims to have also marketed. The ball contained a mixture of
completely cured asthma through the continued glycyrrhiza and white hellebore (Veratrum vide)
use of inhalations. He employed the use of sodium together with a tarry residue smelling of carbolic
chloride inhalations to soften the viscid mucus, acid. The device cost ten shillings and was
and oil of turpentine to stimulate the mucus refillable for five shillings — see Figure 8.
glands. Waldenburg also devised an apparatus for The Carbolic Smoke Ball occupies an important

o up
delivering medicinal gases which he used place in history, not only in terms of the evolution

G r
ays
alongside the other inhalations. of dry powder inhalers but also in law. It was

irw
advertised as being a positive cure for a range of
The first nebulisation devices
ct ic e A
respiratory conditions including influenza, asthma,

r a l P r a it e d
bronchitis, croup, whooping cough and many

n e
e spray and theion Pro
Da Costa published a fine account of inhalation
h ib
others. Testimonials from many notable people

r ig h t G
medications and devices in 1867. 20
Among the
c t
were also published. The advertisement offered a

Siegle’so p y
devices described are
C
the hand-ball
r o d u
p 7). Siegle’s
£100 reward to anyone who contracted influenza
steam spray
R eFigure
inhaler — a German
from the early 1860’s (see
invention having used the Carbolic Smoke Ball according to
the directions. Mrs Calill, despite using her Carbolic
steam spray used the Venturi principle to atomise Smoke Ball in accordance with the directions,
liquid medication, and this was, in effect, the contracted influenza. Her claim for £100
beginning of nebuliser therapy. compensation was ignored by the manufacturer and
Writing in 1878, Berkart identified the use of so her husband, a solicitor, sued. When the case
turpentine and assafoetida as a mucolytic,21 and came to trial in 1892, the defence vigorously argued
commented how they were best administered as that the advertisement did not constitute a binding
inhalations. He also describes a “spray-producing obligation, but the judge found for Mrs Calill, a
apparatus” about which he expressed some decision that was supported in the Court of Appeal.
disappointment, which he rationalised as being This established the legal principle that offers made
due to the spray not always helping the deeper through advertising constitute a legal contract, and
structures of the lung. The importance of droplet consequently the Carbolic Smoke Ball Company
size is now much more thoroughly understood and modified its advertising, focussing instead on the
controlled in modern nebulisers. testimonials of famous users. Mrs Calill lived to the
age of 96, eventually dying of influenza in 1942 …
During the 1880’s through to the early 1900’s
The age of advertising and the there was a proliferation of inhalers and inhalants
entrepreneur produced both in the USA and in Europe. The age of
the ‘quack cure’ had truly begun and the
Frederick Roe patented the Carbolic Smoke Ball in entrepreneurial spirit was applied to curing asthma.
1889 as a ‘device to facilitate the distribution, New plastic materials such as Gutta Percha and
inhalation, and application of medicated Bakelite became available. Distribution systems for
powders’.22 The patent describes a hollow rubber supplying drugs further afield improved and
ball with a sieve across the orifice to de- advertising of medicines became commonplace. All
agglomerate the powder inside. When squeezed, a these aspects contributed to feed the expanding
cloud of powder was produced. A glass version was demand for such ‘cures’. Inhalers were not the only

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 Copyright: General Practice Airways Group 2007
Inhalation therapy: an historical review 77

G r o up
A irw ays
r a ct ic e
e ra l P h ib it e d
t G e n n P ro
ig h t i o
Copyr uc
Figure 8 An advertisement for the Carbolic Smoke Ball, 1889

p ro d
Re

Figure 9 Collage of adverts of various inhalers from around 100 years ago

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 Copyright: General Practice Airways Group 2007
78 M. Sanders

advertised cures for asthma though — magnetism,

ultra-violet rays and numerous pills, creams and
potions were also promoted.

Notable inhalers and inhaled therapies from

a hundred years ago
Antiseptic inhalation. Following Lister’s hugely
important discovery of antiseptic surgery the
notion of inhaled antiseptics was promulgated.
Coal tar derivatives such as Vapocresolene were
promoted. Booth’s Hyomei was another heavily
promoted medication that provided ‘dry air’ from
a small bakelite inhaler. The Cigar Inhaler was a Figure 10 The pillow inhaler
clever discreet design for discreet inhalation of
the antiseptic substance Gomenol. Dr Worst’s
inhaler, a beautifully crafted nickel plated device
was patented in 1901. Compound Oxygen was
another heavily promoted cure that relied heavily
on testimonial advertising. A collage of adverts is
shown in Figure 9.

up
Ceramic inhalers. Numerous versions of the

G r o
ays
Nelson inhaler and other ceramic inhalers

irw
appeared to deliver medicinal products. In Europe

ct ic e A
the enamel inhalers fulfilled a similar purpose.

ra l P r a
Pillow inhaler. This clever approach involved the
it e d
e h ib
Figure 11 Various powders used in combustible inhalers

n ro
use of a small shallow pot in a specially made

h t G e i o n P
pillow. Volatile inhalants were put into the pot and
ig t
Copyr o d uc
these were vapourised through the night, delivering

Re p r
medication to the sleeping patient — see Figure 10.
Combustible powders. These were to be burnt
and the arising vapour inhaled. Most contained
stramonium plus other alkaloids such as
belladonna and lobelia. Well known examples
include Braters Powder, Kinsman Powder, Green
Mountain Powder, Kellogg’s Powder, Schiffmann’s
Powder, and Himrod’s — see Figure 11. Many were
also produced as asthma cigarettes (see Figure 12)
and as a pipe mixture. Figure 12 Asthma cigarettes
Menthol inhalers. Menthol and eucalyptus oil
are well known today as over-the-counter
therapies for cough and cold relief. Since Gaubius
in 1774 first extracted crystals from peppermint
oil, later to be known as menthol, inventors have
been finding ways of delivering its cooling vapours
to the respiratory tract.
Oxygen bars. These were first developed in the
1890s and were reported in Scientific American
(Supplement 999 Feb 23 1895). Just like today,
customers would inhale purified oxygen at a bar. In
France, an establishment was set up in 1891 by
Doctors Labbé, Oudin & Desnos for treating patients
with anaemia and tuberculosis; it was located in
Saint Raphael, France, beneath a casino. Ozone was
generated on the premises by ozonizers and was
available in two concentrations — see Figure 13. Figure 13 Depiction of an Oxygen Bar, 1890's

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 Copyright: General Practice Airways Group 2007
Inhalation therapy: an historical review 79

Figure 15 The Abbott Aerohaler, 1948

successful use of nebulised adrenalin in an oxygen

stream. Adrenalin Chloride (epinephrine) solution
1:100 was supplied in the 1930’s as a bronchial
muscle relaxant, to reverse constriction; it was
Figure 14 The Maxim inhaler, 1909 vapourised through electrical compressors such as

up
the Pneumostat or by hand nebulisers such as the

G r o
ays
Maxim inhaler. Sir Hiram Maxim, an American Parke-Davis Glaseptic. Adrenalin was a life-saving

irw
living in London, was an inveterate inventor. Most drug but had significant associated problems.

ct ic
famous for the Maxim machine gun, he also
e A The use of atropine for the treatment of asthma

l P r a
invented a steam driven flying machine! In August
ra it e d
was also being explored at this time. Von Terray

e n e ro
1909, plagued by the effects of the London
P h ib claimed that atropine given hypodermically was a

g h t G i o n
atmosphere, he developed and patented his own
i t
specific treatment for asthma. Weiss found good

Copyr o d uc
inhaler. It resembled a glass retort and delivered a results from spraying it through the mouth.

Re p r
combination of menthol and pine essence (dirigo),
and was known as the Pipe of Peace. The pack
Throughout the early 20th century there were
some notable inhaler inventions:
included a separate bulbous glass inhaler for nasal • In the 1920s, the first mention of the inhalation
delivery of menthol — see Figure 14. of atropine from an atomizer was made by Hurst.
• In 1924, Schmid and Chen, whilst investigating
Ma Huang, identified ephedrine24 — a substance
The end of the entrepreneur and the similar to adrenaline. This alkaloid was
age of the scientist subsequently used by inhalation.
• In the 1930s, early compressor nebulisers (such
Controls on advertising and promotion imposed by as the Pneumstat) were used to deliver adrenal
the FDA in 1906 sounded a death knell for the extracts and papaverin (Bronchovydrin).
entrepreneurial quack cures, and the scientist • In 1940, isoprenaline was first described by
took over. The general trend was that nationally Konzett, and it rapidly became available for
produced and licensed products superseded inhalation.
locally produced devices. • In 1948, Abbott launched the Aerohalor with a
In 1900 Solis-Cohen first used adrenal extracts preparation of penicillin for inhalation.
to treat asthma considered to be due to vasomotor Additionally a further presentation of the
ataxia.23 The following year Bartlett advised the bronchodilator Norethisderone was also made
use of 2 grains of dessicated adrenal extract three available. The Abbott Aerohalor, a dry powder
times a day. In 1904, Kaplin and Bullowe identified inhaler, used a lactose-based formulation to
the value of adrenalin in asthma and it went on to deliver penicillin from small capsules known as
become the foundation of what we can consider to ‘sifters’ — see Figure 15.
be modern pharmaceutical inhalation therapy. • In 1950, Reeder and Mackay treated pneumonia
From 1910 onwards experiments into the delivery with inhaled corticosteroid, leading to intensive
of adrenalin began. Pick, in 1911, reported investigation into the use of inhaled anti-
successful nebulisation of adrenalin in two inflammatories. Gelfrand, in 1951, reported on
patients. In 1929 Camps reported on the five patients who were treated with nebulised

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 Copyright: General Practice Airways Group 2007
80 M. Sanders

cortisone. In 1955, Foulds used hydrocortisone bronchodilators, relatively free from secondary
in powder form. This work was ultimately to effects on other systems. Salbutamol was
lead to the discovery of beclomethasone nearly formulated in a pMDI, as a dry powder inhaler in the
20 years later. Rotahaler and the Diskhaler, and was also produced
as nebulised, tablet and syrup formulations.
The Rotahaler, a dry powder capsule inhaler,
Modern times simply required twisting for a loaded capsule to be
pulled apart and the powder to be inhaled through
Undoubtedly the most significant event of the a mesh. The Diskhaler represented an important
1950’s was the development in 1955 of the step forward because it did not require reloading
pressurised metered dose inhaler (pMDI).25 Charles for every dose, so it was the first multi-unit dose
Thiel working at Riker (3M) was one of the key dry powder inhaler. This inhaler used a cartridge
workers in the team that developed cold-fill pMDIs with foiled sealed pre-measured doses that were
using special valves developed by Philip perforated at the time of use to permit the drug
Maschberg. The products were shown to be to be inhaled.
effective in studies conducted by Dr Carr at the In 1972 Allen & Hanbury’s marketed the first
Veterans Administration Hospital (Long Beach, inhaled steroid, beclomethasone, in the same
California) in June 1955 and new drug applications inhalers as salbutamol. Numerous steroids have
(NDAs) filed in January 1956 were approved in subsequently been developed, and some have led
March the same year. Medihaler-iso (isoprenaline) to new inhaler developments.
and Medihaler-epi (adrenalin) were launched in The Allen & Hanbury’s technology was refined

up
late March 1956. Nowadays, pMDIs have become a
o
and substantially improved in the Diskus (Accuhaler)

G r
ays
very important inhalation technology with annual which has proved outstandingly popular and which

irw
sales currently in excess of 400 million units. The
A
is used to administer bronchodilator and anti-

ct ic
drugs, of course, have been updated and the

r a e inflammatory drugs and also combinations of the two.

l P t e d
propellant technology improved through the use
i
In 1987, Astra Zeneca launched a novel steroid,

e n e ra ro h i
of less environmentally-damaging HFAs. The use of
b budesonide, in a new multi-dose dry powder

ig h t G t i o n P
pMDIs has, however, been limited by several inhaler that did not depend on each dose being

Copyr o d uc
drawbacks: the need to co-ordinate the inhalation
r
isolated; rather, the drug substance was kept in a

Re p
and the actuation can prove difficult for patients;
the inhalers have lacked dose-counters; and their
reservoir from which individual doses were taken
at administration. This device, the Turbuhaler, has
ability to deliver large doses of drug is limited. also proved very popular and in a similar way is
Bengers Laboratories (subsequently acquired by now used to administer bronchodilators, inhaled
Fison’s Pharmaceuticals) were engaged in testing steroid, and combinations of the two.
the anti-allergic properties of synthetic cromone Subsequent development of dry powder inhalers
derivatives of khellin (an Egyptian plant) during has followed the three themes described above:
the early 1960’s. Dr Roger Altounyan, the real-life capsule inhalers; the multiple-unit dose inhalers;
‘Roger’ of Swallows and Amazons fame, himself an and the reservoir devices.
asthmatic, personally tested the compounds. A
former Spitfire pilot who was very familiar with
aerodynamics, he invented the Spinhaler, a Conclusion
capsule inhaler that used a small propeller to
create turbulence. It was necessary to find There is a rich history of ingenuity and
alternatives to the standard pMDI technology inventiveness that has accompanied the
because the dose to be delivered exceeded the development of inhalation therapy throughout the
capability of pMDI metering valves. Intal (sodium ages. Our understanding of the engineering,
cromoglycate) was launched in 1967 as a Spinhaler pharmacological, and medical science involved has
device. Some years later a pMDI version was improved vastly. At the same time we have now
created, using a lower dose. lifted our sights higher, aiming to use inhalation
The following year, 1968, the remarkable therapy to treat diseases that involve systems
bronchodilator actions of salbutamol were other than the lungs. New inventions await.
described by Lunts, working at Allen and Hanbury’s.
Having been first synthesised in 1966, it was
marketed in 1969 as Ventolin, and rapidly became Conflict of interest declaration
the most prescribed bronchodilator globally.
Salbutamol was the first of the selective The author is employed by Pharmaxis Ltd, holds

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Inhalation therapy: an historical review 81

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