Note: Descriptions are shown in the official language in which they were submitted.
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This invention relates to apparatus for converting liquid composi-
tions into aerosol form for inhalation and is particularly concerned with ato-
mizers which contain a piezo-electric oscillation system and which may be used
for the administration as aerosols of liquid compositions containing medica-
ments, and to a method for making an atomizer plate.
~ or certain purposes, for example the administration of antibio-
tic substances for bronchospasmolysis, it is essential that pharmaceutical
compositions which are inhaled in aerosol form should reach the lung, where
they are active. For this to occur the inhaled compositions must be in the
form of small droplets. If the droplets are too large they tend to precipi-
tate prematureiy on inhalation, e.g. in the mouth or in the upper airways, so
that the medicaments are ineffective or their desired effect is achieved to
a lesser degree.
Aerosol devices which function by means of atomization of liquids
at an atomizer plate coupled to the oscillations of a piezo-electric oscilla-
tion system are described for example in German Offenlegungsschriften P 20 32
433, P 23 08 584, P 24 45 791, P 25 37 765 and P 26 37 162. These devices in
general suffer from the disadvantage of producing too gr~at a proportion of
droplets which are too large and which precipitate prematurely on inhalation.
It is an object of the present invention to provide an apparatus
capable of producing an aerosol having a high proportion of small droplets,
especially droplets which are sufficiently small so as to avoid premature
precipitation on inhalation.
We have found that such an object may be achieved by providing
the atomizer plate of a conventional device ~for example as described in the
offenlegungsschriften mentioned above) with a coating comprising a thin film
of one or more elastomers.
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Accordingly the present invention provides an apparatus for use in
converting a liquid composition into aerosol form for inhalation, which
apparatus comprises an oscillatory atomizer plate having a working surface
positioned so as in use to receive the liquid composition and a piezo-electric
system which in use controls the oscillatory movement of the atomizer plate
whereby the liquid composition received on the said working surface is con-
verted into aerosol form for inhalation, the working surface of the atomizer
plate being provided with a film of an elastomeric composition having a thick-
ness of 50 to 500 ~m.
According to a further feature of the present invention, there is
provided an atomizer plate adapted for use in an apparatus according to the
invention as hereinbefore defined and having a working surface provided with
a film of an elastomeric composition whose thickness is in the range o~ from
50 to 500 ~m. The elastomeric film should be thin and preferably has a thick-
ness of from 100 to 300 ~m. The film can comprise elastomers of many different
types, alone or mixed with alastomers or with other materials. Polyurethanes
are an example of a suitable class of elastomers.
According to a still further aspect of the invention, there is pro-
vided a method of making an atomizer plate for use in an apparatus for con-
verting a liquid into aerosol form for inhalation, comprising the steps of
i cleaning the plate with a cleaning agent;
ii applying to the surface of the plate a polyurethane precursor
comprising a 50% solution of di-isocyanatephenylmethane and a polyvalent poly-
ether alcohol in anhydrous toluene adjusted to a viscosity of 23 poise;
iii arranging the plate in a horizontal position to produce an
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homogeneous layer;
iv curing the coating in a humid atmosphere for 24 hours at approx-
imately 18C and 50% relative humidity, to coat the plate with a film whose
thickness is in the range of from 50 to 500 ~m.
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The atomizer plate is desirably made from a metal having approp-
riate physical and chemical properties, for example stainless steel. The
elastomers may be applied to the surface of the plate for example in the form
of concentrated solutions in suitable solvents, e.g. organic solvents, from
which the solvent may be removed by evaporation, or the elastomers may be
applied in the form of monomers and/or prepolymers, optionally in solution
and polymerization may take place in situ followed by evaporation of solvent
where necessary. For example polyurethanes may be polymerized in situ on the
atomizer plate which in that case requires no previous treatment other than
to ensure that it is thoroughly clean. In some circumstances (especially
where elastomers other than polyurethanes are used) treatment of the surface
of the plate with a primer may improve bonding of the elastomer to the plate.
The invention will now be more particularly described in the fol-
lowing non-limiting examples.
Example 1: Preparation of an Atomization Apparatus of the Invention
The working surface of the atomizer plate ~made of stainless
steel) of an inhalation apparatus according to German Offenlegungsschrift 2
308 584 is cleaned with methylene chloride. A polyurethane precursor consist-
ing of 50 mg of a 50% solution of di-isocyanatephenylmethane and a polyvalent
polyether alcohol in anhydrous ~oluene, adjusted to a viscosity of 23 poise,
is applied to the working surface. With the atomizer plate in horizontal
position, the mixture distributes over the working surface in such a way that
a homogeneous layer is produced. The coating is cured in a humid atmosphere,
curing being generally finished after 24 hours at approx. 18C and 50% rela-
tive humidity. A film of 200 ~m thickness with a breaking tension of 340%
and a tensile strength of 0.35 kg results.
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ExampIe 2 Comparative Tests
Tests were performed on dogs in which bronchospasm was induced
with acetyl chloride. A dose of 200 ~g of fenoterol was administered in each
case. The apparatus coated as in example 1 was tested against a commercial
metering aerosol functioning by propellant gas delivering the above dose upon
valve actuation and against an apparatus constructed in accordance with
German Qffenlegungsschift 2 308 584 having an uncoated atomizer plate. The
effect of the dose adminis~ered by the apparatus of the invention was equi-
; valent to that delivered by the metering aerosol. The apparatus with the un-
coated atomizer plate however had no noticeable effect on the tested animals.
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