Note: Descriptions are shown in the official language in which they were submitted.
CA 03118060 2021-04-28
WO 2020/089640 PCT/GB2019/053095
AEROSOLISABLE FORMULATION
FIELD OF THE INVENTION
The present disclosure relates to an aerosolisable formulation, a method of
forming the
same, a container containing the same, a device containing the same and
processes and
uses of the same.
BACKGROUND TO THE INVENTION
Electronic aerosol provision systems such as e-cigarettes generally contain a
reservoir of
liquid which is to be vaporised, typically containing nicotine. When a user
inhales on the
device, a heater is activated to vaporise a small amount of liquid, which is
therefore inhaled
by the user.
The use of e-cigarettes in the UK has grown rapidly, and it has been estimated
that there are
now over a million people using them in the UK.
One challenge faced in providing such systems is to provide from the aerosol
provision
device an aerosol to be inhaled which provides consumers with an acceptable
experience.
Some consumers may prefer an e-cigarette that generates an aerosol that
closely 'mimics'
smoke inhaled from a tobacco product such as a cigarette. Aerosols from e-
cigarettes and
smoke from tobacco products such as cigarettes provides to the user a complex
chain of
flavour in the mouth, nicotine absorption in the mouth and throat, followed by
nicotine
absorption in the lungs. These various aspects are described by users in terms
of flavour,
intensity/quality, impact, irritation/smoothness and nicotine reward. Nicotine
contributes to a
number of these factors, and is strongly associated with factors such as
impact, irritation and
smoothness; these are readily perceived by consumers, and e-cigarettes may
offer too much
or too little of these parameters for consumers, depending upon individual
preferences.
Nicotine reward is particularly complex as it results from both the amount of
and speed with
which nicotine is absorbed from the lining of the mouth, this is typically
nicotine in the vapour
phase, and from the amount and speed nicotine that is absorbed from the lungs,
this is
typically nicotine in the particulate phase of the aerosol which is inhaled.
Each of these
factors, and their balance, can strongly contribute to consumer acceptability
of an e-
cigarette. Providing means to optimise the overall vaping experience is
therefore desirable to
e-cigarette manufacturers.
1
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
A further challenge facing such systems is the continued demand for harm
reduction. Harm
from cigarette and e-cigarette devices primarily comes from toxicants.
Therefore, there is a
desire to reduce or remove the components which may form toxicants.
SUMMARY OF THE INVENTION
In one aspect there is provided an aerosolisable formulation comprising
(i) water in an amount of at least 50 wt.% based on the aerosolisable
formulation; and
(ii) nicotine;
wherein the nicotine is present in an amount of no greater than lwt.c/o based
on the
aerosolisable formulation.
In one aspect there is provided a process for forming an aerosol, the process
comprising
aerosolising an aerosolisable formulation comprising
(i) water in an amount of at least 50 wt.% based on the aerosolisable
formulation; and
(ii) nicotine;
wherein the nicotine is present in an amount of no greater than lwt.c/o based
on the
aerosolisable formulation.
In one aspect there is provided a contained aerosolisable formulation
comprising
(a) a container; and
(b) an aerosolisable formulation comprising
(i) water in an amount of at least 50 wt.% based on the aerosolisable
formulation;
and
(ii) nicotine;
wherein the nicotine is present in an amount of no greater than lwt.c/o based
on the
aerosolisable formulation.
In one aspect there is provided an electronic aerosol provision system
comprising:
(a) an aerosoliser for aerosolising formulation for inhalation by a user of
the electronic
aerosol provision system;
(b) a power supply comprising a cell or battery for supplying power to the
aerosoliser
(c) an aerosolisable formulation comprising
(i) water in an amount of at least 50 wt.% based on the aerosolisable
formulation;
and
(ii) nicotine;
wherein the nicotine is present in an amount of no greater than lwt.c/o based
on the
2
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
aerosolisable formulation.
DETAILED DESCRIPTION
As discussed herein is provided an aerosolisable formulation comprising (i)
water in an
amount of at least 50 wt.% based on the aerosolisable formulation; and (ii)
nicotine; wherein
the nicotine is present in an amount of no greater than 1wt.% based on the
aerosolisable
formulation. We have found that an advantageous system may be provided in
which an
aerosolisable formulation contains water in an amount of at least 50 wt.%
based on the
aerosolisable formulation and contains nicotine in an amount of no greater
than 1wt.% based
on the aerosolisable formulation. We have surprising found that in such a high
water system,
providing nicotine in a maximum amount of no greater than 1wt.% provides the
optimum
sensory perception for the user. In particular, control of nicotine to this
maximum amount
provides a nicotine 'hit' and/or sensory perception preferred by users. This
desirable nicotine
'hit' and/or flavour release is in contrast to 'traditional' e-liquids based
on glycerol and
propylene glycol which users sometimes do not use because of perceived
differences in
respect of nicotine 'hit' and/or flavour release provided by tobacco based
cigarettes.
We have also identified that water-based system may be provided in which
aerosolised
formulation is formed from an aerosolisable formulation at a low temperature.
This is in
contrast to 'traditional' e-cigarettes which use a heater, typically applied
to liquids based on
glycerol and propylene glycol to form an aerosolised formulation. The
provision of such a
system and the avoidance of heating may address problems of the prior art
relating to the
formation of toxicants. More specifically, we have identified a water-based
system which, by
selection of a very high water content delivers desirable nicotine 'hit'
and/or flavour release
but avoids the need to use the heaters associated with prior liquids based on
glycerol and
propylene glycol. In the present system, the number of components present may
be reduced
leading to less chance of forming breakdown products/toxicants. In particular,
the use of
water allows for the replacement of some or all of the glycerol, propylene
glycol, 1,3-propane
diol and mixtures thereof typically used in e-cigarettes.
For ease of reference, these and further aspects of the present invention are
now discussed
under appropriate section headings. However, the teachings under each section
are not
necessarily limited to each particular section.
Water
3
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
As discussed herein the aerosolisable formulation comprises water in an amount
of at least
50 wt.% based on the aerosolisable formulation. In one aspect water is present
in an amount
of at least 55 wt.% based on the aerosolisable formulation. In one aspect
water is present in
an amount of at least 60 wt.% based on the aerosolisable formulation. In one
aspect water is
present in an amount of at least 65 wt.% based on the aerosolisable
formulation. In one
aspect water is present in an amount of at least 70 wt.% based on the
aerosolisable
formulation. In one aspect water is present in an amount of at least 75 wt.%
based on the
aerosolisable formulation. In one aspect water is present in an amount of at
least 80 wt.%
based on the aerosolisable formulation. In one aspect water is present in an
amount of at
least 85 wt.% based on the aerosolisable formulation. In one aspect water is
present in an
amount of at least 90 wt.% based on the aerosolisable formulation. In one
aspect water is
present in an amount of at least 95 wt.% based on the aerosolisable
formulation. In one
aspect water is present in an amount of at least 99 wt.% based on the
aerosolisable
formulation.
In one aspect water is present in an amount of from 50 to 99 wt.% based on the
aerosolisable formulation. In one aspect water is present in an amount of from
55 to 99 wt.%
based on the aerosolisable formulation. In one aspect water is present in an
amount of from
60 to 99 wt.% based on the aerosolisable formulation. In one aspect water is
present in an
amount of from 65 to 99 wt.% based on the aerosolisable formulation. In one
aspect water is
present in an amount of from 70 to 99 wt.% based on the aerosolisable
formulation. In one
aspect water is present in an amount of from 75 to 99 wt.% based on the
aerosolisable
formulation. In one aspect water is present in an amount of from 80 to 99 wt.%
based on the
aerosolisable formulation. In one aspect water is present in an amount of from
85 to 99 wt.%
based on the aerosolisable formulation. In one aspect water is present in an
amount of from
90 to 99 wt.% based on the aerosolisable formulation. In one aspect water is
present in an
amount of from 95 to 99 wt.% based on the aerosolisable formulation.
As discussed herein the use of water allows for the replacement of some or all
of the
glycerol, propylene glycol, 1,3-propane diol and mixtures thereof typically
used in e-
cigarettes. In one aspect the aerosolisable formulation contains glycerol,
propylene glycol,
1,3-propane diol and mixtures thereof in a combined amount of no greater than
10 wt.%
based on the aerosolisable formulation or based on the aerosolisable
formulation. In one
aspect the aerosolisable formulation contains glycerol, propylene glycol, 1,3-
propane diol
and mixtures thereof in a combined amount of no greater than 8 wt.% based on
the
aerosolisable formulation or based on the aerosolisable formulation. In one
aspect the
aerosolisable formulation contains glycerol, propylene glycol, 1,3-propane
diol and mixtures
4
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
thereof in a combined amount of no greater than 5 wt.% based on the
aerosolisable
formulation or based on the aerosolisable formulation. In one aspect the
aerosolisable
formulation contains glycerol, propylene glycol, 1,3-propane diol and mixtures
thereof in a
combined amount of no greater than 2 wt.% based on the aerosolisable
formulation or based
on the aerosolisable formulation. In one aspect the aerosolisable formulation
contains
glycerol, propylene glycol, 1,3-propane diol and mixtures thereof in a
combined amount of no
greater than 1 wt.% based on the aerosolisable formulation or based on the
aerosolisable
formulation. In one aspect the aerosolisable formulation contains glycerol,
propylene glycol,
1,3-propane diol and mixtures thereof in a combined amount of no greater than
0.5 wt.%
based on the aerosolisable formulation or based on the aerosolisable
formulation. In one
aspect the aerosolisable formulation contains glycerol, propylene glycol, 1,3-
propane diol
and mixtures thereof in a combined amount of no greater than 0.2 wt.% based on
the
aerosolisable formulation or based on the aerosolisable formulation. In one
aspect the
aerosolisable formulation contains glycerol, propylene glycol, 1,3-propane
diol and mixtures
thereof in a combined amount of no greater than 0.1 wt.% based on the
aerosolisable
formulation or based on the aerosolisable formulation. In one aspect the
aerosolisable
formulation contains glycerol, propylene glycol, 1,3-propane diol and mixtures
thereof in a
combined amount of no greater than 0.01 wt.% based on the aerosolisable
formulation or
based on the aerosolisable formulation. In one aspect the aerosolisable
formulation contains
no glycerol, propylene glycol, 1,3-propane diol and mixtures thereof.
In one aspect the aerosolisable formulation contains glycerol, propylene
glycol, and mixtures
thereof in a combined amount of no greater than 10 wt.% based on the
aerosolisable
formulation or based on the aerosolisable formulation. In one aspect the
aerosolisable
formulation contains glycerol, propylene glycol, and mixtures thereof in a
combined amount
of no greater than 8 wt.% based on the aerosolisable formulation or based on
the
aerosolisable formulation. In one aspect the aerosolisable formulation
contains glycerol,
propylene glycol, and mixtures thereof in a combined amount of no greater than
5 wt.%
based on the aerosolisable formulation or based on the aerosolisable
formulation. In one
aspect the aerosolisable formulation contains glycerol, propylene glycol, and
mixtures
thereof in a combined amount of no greater than 2 wt.% based on the
aerosolisable
formulation or based on the aerosolisable formulation. In one aspect the
aerosolisable
formulation contains glycerol, propylene glycol, and mixtures thereof in a
combined amount
of no greater than 1 wt.% based on the aerosolisable formulation or based on
the
aerosolisable formulation. In one aspect the aerosolisable formulation
contains glycerol,
propylene glycol, and mixtures thereof in a combined amount of no greater than
0.5 wt.%
based on the aerosolisable formulation or based on the aerosolisable
formulation. In one
5
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
aspect the aerosolisable formulation contains glycerol, propylene glycol, and
mixtures
thereof in a combined amount of no greater than 0.2 wt.% based on the
aerosolisable
formulation or based on the aerosolisable formulation. In one aspect the
aerosolisable
formulation contains glycerol, propylene glycol, and mixtures thereof in a
combined amount
of no greater than 0.1 wt.% based on the aerosolisable formulation or based on
the
aerosolisable formulation. In one aspect the aerosolisable formulation
contains glycerol,
propylene glycol, and mixtures thereof in a combined amount of no greater than
0.01 wt.%
based on the aerosolisable formulation or based on the aerosolisable
formulation. In one
aspect the aerosolisable formulation contains no glycerol, propylene glycol,
and mixtures
thereof.
In one aspect the aerosolisable formulation contains glycerol in an amount of
no greater than
10 wt.% based on the aerosolisable formulation or based on the aerosolisable
formulation. In
one aspect the aerosolisable formulation contains glycerol in an amount of no
greater than 8
wt.% based on the aerosolisable formulation or based on the aerosolisable
formulation. In
one aspect the aerosolisable formulation contains glycerol in an amount of no
greater than 5
wt.% based on the aerosolisable formulation or based on the aerosolisable
formulation. In
one aspect the aerosolisable formulation contains glycerol in an amount of no
greater than 2
wt.% based on the aerosolisable formulation or based on the aerosolisable
formulation. In
one aspect the aerosolisable formulation contains glycerol in an amount of no
greater than 1
wt.% based on the aerosolisable formulation or based on the aerosolisable
formulation. In
one aspect the aerosolisable formulation contains glycerol in an amount of no
greater than
0.5 wt.% based on the aerosolisable formulation or based on the aerosolisable
formulation.
In one aspect the aerosolisable formulation contains glycerol in an amount of
no greater than
0.2 wt.% based on the aerosolisable formulation or based on the aerosolisable
formulation.
In one aspect the aerosolisable formulation contains glycerol in an amount of
no greater than
0.1 wt.% based on the aerosolisable formulation or based on the aerosolisable
formulation.
In one aspect the aerosolisable formulation contains glycerol in an amount of
no greater than
0.01 wt.% based on the aerosolisable formulation or based on the aerosolisable
formulation.
In one aspect the aerosolisable formulation contains no glycerol.
In one aspect the aerosolisable formulation contains propylene glycol in an
amount of no
greater than 10 wt.% based on the aerosolisable formulation or based on the
aerosolisable
formulation. In one aspect the aerosolisable formulation contains propylene
glycol in an
amount of no greater than 8 wt.% based on the aerosolisable formulation or
based on the
aerosolisable formulation. In one aspect the aerosolisable formulation
contains propylene
glycol in an amount of no greater than 5 wt.% based on the aerosolisable
formulation or
6
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
based on the aerosolisable formulation. In one aspect the aerosolisable
formulation contains
propylene glycol in an amount of no greater than 2 wt.% based on the
aerosolisable
formulation or based on the aerosolisable formulation. In one aspect the
aerosolisable
formulation contains propylene glycol in an amount of no greater than 1 wt.%
based on the
aerosolisable formulation or based on the aerosolisable formulation. In one
aspect the
aerosolisable formulation contains propylene glycol in an amount of no greater
than 0.5 wt.%
based on the aerosolisable formulation or based on the aerosolisable
formulation. In one
aspect the aerosolisable formulation contains propylene glycol in an amount of
no greater
than 0.2 wt.% based on the aerosolisable formulation or based on the
aerosolisable
formulation. In one aspect the aerosolisable formulation contains propylene
glycol in an
amount of no greater than 0.1 wt.% based on the aerosolisable formulation or
based on the
aerosolisable formulation. In one aspect the aerosolisable formulation
contains propylene
glycol in an amount of no greater than 0.01 wt.% based on the aerosolisable
formulation or
based on the aerosolisable formulation. In one aspect the aerosolisable
formulation contains
no propylene glycol.
Nicotine
Nicotine formulations may be provided having desirable properties of flavour,
impact,
.. irritation, smoothness and/or nicotine reward for the user. In one aspect
nicotine is present in
an amount of no greater than 0.9wt.c/o based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of no greater than
0.8wt.c/o based
on the total weight of the aerosolisable formulation. In one aspect nicotine
is present in an
amount of no greater than 0.7wt.c/o based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of no greater than
0.6wt.c/o based
on the total weight of the aerosolisable formulation. In one aspect nicotine
is present in an
amount of no greater than 0.5wt.c/o based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of no greater than
0.4wt.c/o based
on the total weight of the aerosolisable formulation. In one aspect nicotine
is present in an
amount of no greater than 0.3wt.c/o based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of no greater than
0.2wt.c/o based
on the total weight of the aerosolisable formulation. In one aspect nicotine
is present in an
amount of no greater than 0.15wt.c/o based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of no greater than
0.1wt.c/o based
on the total weight of the aerosolisable formulation.
In one aspect nicotine is present in an amount of from 0.01 to 1 wt% based on
the total
7
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
weight of the aerosolisable formulation. In one aspect nicotine is present in
an amount of
from 0.02 to 1 wt% based on the total weight of the aerosolisable formulation.
In one aspect
nicotine is present in an amount of from 0.05 to 1 wt% based on the total
weight of the
aerosolisable formulation. In one aspect nicotine is present in an amount of
from 0.08 to 1
wt% based on the total weight of the aerosolisable formulation. In one aspect
nicotine is
present in an amount of from 0.1 to 1 wt% based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of from 0.15 to 1
wt% based on
the total weight of the aerosolisable formulation. In one aspect nicotine is
present in an
amount of from 0.01 to 0.8 wt% based on the total weight of the aerosolisable
formulation. In
one aspect nicotine is present in an amount of from 0.02 to 0.8 wt% based on
the total
weight of the aerosolisable formulation. In one aspect nicotine is present in
an amount of
from 0.05 to 0.8 wt% based on the total weight of the aerosolisable
formulation. In one
aspect nicotine is present in an amount of from 0.08 to 0.8 wt% based on the
total weight of
the aerosolisable formulation. In one aspect nicotine is present in an amount
of from 0.1 to
0.8 wt% based on the total weight of the aerosolisable formulation. In one
aspect nicotine is
present in an amount of from 0.15 to 0.8 wt% based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of from 0.01 to
0.5 wt% based on
the total weight of the aerosolisable formulation. In one aspect nicotine is
present in an
amount of from 0.02 to 0.5 wt% based on the total weight of the aerosolisable
formulation. In
one aspect nicotine is present in an amount of from 0.05 to 0.5 wt% based on
the total
weight of the aerosolisable formulation. In one aspect nicotine is present in
an amount of
from 0.08 to 0.5 wt% based on the total weight of the aerosolisable
formulation. In one
aspect nicotine is present in an amount of from 0.1 to 0.5 wt% based on the
total weight of
the aerosolisable formulation. In one aspect nicotine is present in an amount
of from 0.15 to
0.5 wt% based on the total weight of the aerosolisable formulation. In one
aspect nicotine is
present in an amount of from 0.01 to 0.4 wt% based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of from 0.02 to
0.4 wt% based on
the total weight of the aerosolisable formulation. In one aspect nicotine is
present in an
amount of from 0.05 to 0.4 wt% based on the total weight of the aerosolisable
formulation. In
one aspect nicotine is present in an amount of from 0.08 to 0.4 wt% based on
the total
weight of the aerosolisable formulation. In one aspect nicotine is present in
an amount of
from 0.1 to 0.4 wt% based on the total weight of the aerosolisable
formulation. In one aspect
nicotine is present in an amount of from 0.15 to 0.5 wt% based on the total
weight of the
aerosolisable formulation. In one aspect nicotine is present in an amount of
from 0.01 to 0.3
wt% based on the total weight of the aerosolisable formulation. In one aspect
nicotine is
present in an amount of from 0.02 to 0.3 wt% based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of from 0.05 to
0.3 wt% based on
8
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
the total weight of the aerosolisable formulation. In one aspect nicotine is
present in an
amount of from 0.08 to 0.3 wt% based on the total weight of the aerosolisable
formulation. In
one aspect nicotine is present in an amount of from 0.1 to 0.3 wt% based on
the total weight
of the aerosolisable formulation. In one aspect nicotine is present in an
amount of from 0.15
to 0.3 wt% based on the total weight of the aerosolisable formulation. In one
aspect nicotine
is present in an amount of from 0.01 to 0.3 wt% based on the total weight of
the
aerosolisable formulation. In one aspect nicotine is present in an amount of
from 0.01 to 0.25
wt% based on the total weight of the aerosolisable formulation. In one aspect
nicotine is
present in an amount of from 0.01 to 0.2 wt% based on the total weight of the
aerosolisable
formulation. In one aspect nicotine is present in an amount of from 0.01 to
0.15 wt% based
on the total weight of the aerosolisable formulation. In one aspect nicotine
is present in an
amount of from 0.02 to 0.15 wt% based on the total weight of the aerosolisable
formulation.
In one aspect nicotine is present in an amount of from 0.05 to 0.15 wt% based
on the total
weight of the aerosolisable formulation. In one aspect nicotine is present in
an amount of
from 0.1 to 0.15 wt% based on the total weight of the aerosolisable
formulation.
As is understood by one skilled in the art, nicotine may exist in unprotonated
form,
monoprotonated form or diprotonated form. The structures of each of these
forms are given
below.
N N
H/ 1_4
.3 H \cH3
cH3
Unprotonated nicotine monoprotonated nicotine
diprotonated nicotine
Reference in the specification to protonated form means both monoprotonated
nicotine and
diprotonated nicotine. Reference in the specification to amounts in the
protonated form
means the combined amount of monoprotonated nicotine and diprotonated
nicotine.
Furthermore, when reference is made to a fully protonated formulation it will
be understood
that at any one time there may be very minor amounts of unprotonated nicotine
present, e.g.
less than 1% unprotonated.
In one aspect the formulation may comprise nicotine in protonated form. In one
aspect the
formulation may comprise nicotine in unprotonated form. In one aspect the
formulation
comprises nicotine in unprotonated form and nicotine in monoprotonated form.
In one aspect
9
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
the formulation comprises nicotine in unprotonated form and nicotine in
diprotonated form. In
one aspect the formulation comprises nicotine in unprotonated form, nicotine
in
monoprotonated form and nicotine in diprotonated form.
In one aspect at least 5wtcYo of the nicotine present in the formulation is in
protonated form.
In one aspect at least lOwtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 15wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 20wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 25wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 30wtcY0 of the nicotine present in the formulation is
in protonated form.
In one aspect at least 35wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 40wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 45wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 50wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 55wtcYo of the nicotine present in the formulation is
in protonated form.
In one aspect at least 60wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 65wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 70wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 75wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 80wtcY0 of the nicotine present in the formulation is
in protonated form.
In one aspect at least 85wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 90wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 95wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 99wtc/o of the nicotine present in the formulation is
in protonated form.
In one aspect at least 99.9wtcY0 of the nicotine present in the formulation is
in protonated
form.
In one aspect from 50 to 95 wt% of the nicotine present in the formulation is
in protonated
form. In one aspect from 55 to 95 wt% of the nicotine present in the
formulation is in
protonated form. In one aspect from 60 to 95 wt% of the nicotine present in
the formulation
is in protonated form. In one aspect from 65 to 95 wt% of the nicotine present
in the
formulation is in protonated form. In one aspect from 70 to 95 wt% of the
nicotine present in
the formulation is in protonated form. In one aspect from 75 to 95 wt% of the
nicotine present
in the formulation is in protonated form. In one aspect from 80 to 95 wt% of
the nicotine
present in the formulation is in protonated form. In one aspect from 85 to 95
wt% of the
nicotine present in the formulation is in protonated form. In one aspect from
90 to 95 wt% of
the nicotine present in the formulation is in protonated form.
CA 03118060 2021-04-28
WO 2020/089640 PCT/GB2019/053095
The relevant amounts of nicotine which are present in the formulation in
protonated form are
specified herein. These amounts may be readily calculated by one skilled in
the art. Nicotine,
3-(1-methylpyrrolidin-2-y1) pyridine, is a diprotic base with pKa of 3.12 for
the pyridine ring
and 8.02 for the pyrrolidine ring It can exist in pH-dependent protonated
(mono- and di-) and
non-protonated (free base) forms which have different bioavailability.
f \
H 4. j
(
\ =:::
The distribution of protonated and non-protonated nicotine will vary at
various pH
increments.
-,
K1/41----\ H+ H H r--N f- \
. =
H+
---N- -- ''N:e - ----\---' '' N '=
.,=-) :., ...,:.,
ge
The fraction of non-protonated nicotine will be predominant at high pH levels
whilst a
decrease in the pH will see an increase of the fraction of protonated nicotine
(mono- or di-
depending on the pH). If the relative fraction of protonated nicotine and the
total amount of
nicotine in the sample are known, the absolute amount of protonated nicotine
can be
calculated.
The relative fraction of protonated nicotine in formulation can be calculated
by using the
Henderson-Hasselbalch equation, which describes the pH as a derivation of the
acid
dissociation constant equation, and it is extensively employed in chemical and
biological
systems. Consider the following equilibrium:
B + H+ -"".: BH+
The Henderson-Hasselbalch equation for this equilibrium is:
[B]
pH = pKa + log-,--
IBH +1
Where [B] is the amount of non-protonated nicotine (i.e. free base), [BH+] the
amount of
11
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
protonated nicotine (i.e. conjugate acid) and pKa is the reference pKa value
for the
pyrrolidine ring nitrogen of nicotine (pKa=8.02). The relative fraction of
protonated nicotine
can be derived from the alpha value of the non-protonated nicotine calculated
from the
Henderson-Hasselbalch equation as:
[B]
[Bli +1
%protonatecl nicotine = 100 { [B]
(*100} 1 +
[BH +1
Determination of pKa values of nicotine formulations was carried out using the
basic
approach described in "Spectroscopic investigations into the acid¨base
properties of nicotine
at different temperatures", Peter M. Clayton, Carl A. Vas, Tam T. T. Bui, Alex
F. Drake and
Kevin McAdam, .Anal. Methods, 2013,5, 81-88.
Acid
In one aspect the aerosolisable formulation further comprises an acid. The
acid may be any
suitable acid. In one aspect the acid is an organic acid. In one aspect the
acid is a carboxylic
acid. In one aspect the acid is an organic carboxylic acid.
In one aspect the acid is selected from the group consisting of acetic acid,
lactic acid, formic
acid, citric acid, benzoic acid, pyruvic acid, levulinic acid, succinic acid,
tartaric acid, sorbic
acid, propionic acid, phenylacetic acid, and mixtures thereof. In one aspect
the acid is
selected from the group consisting of citric acid, benzoic acid, levulinic
acid, lactic acid,
sorbic acid, and mixtures thereof. In one aspect the acid is selected from the
group
consisting of citric acid, benzoic acid, levulinic acid, and mixtures thereof.
In one aspect the
acid is at least citric acid. In one aspect the acid consists of citric acid.
In one aspect the acid is selected from acids having a pka of from 2 to 5. In
one aspect the
acid is a weak acid. In one aspect the acid is a weak organic acid.
The acid may be present in any suitable amount. In one aspect the acid is
present in an
amount of no greater than 6 wt% based on the aerosolisable formulation. In one
aspect the
acid is present in an amount of from 0.01 to 6 wt% based on the aerosolisable
formulation.
In one aspect the acid is present in an amount of from 0.02 to 6 wt% based on
the
aerosolisable formulation. In one aspect the acid is present in an amount of
from 0.05 to 6
12
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
wrio based on the aerosolisable formulation. In one aspect the acid is present
in an amount
of from 0.08 to 6 wt% based on the aerosolisable formulation. In one aspect
the acid is
present in an amount of from 0.01 to 5 wt% based on the aerosolisable
formulation. In one
aspect the acid is present in an amount of from 0.02 to 5 wt% based on the
aerosolisable
formulation. In one aspect the acid is present in an amount of from 0.05 to 5
wt% based on
the aerosolisable formulation. In one aspect the acid is present in an amount
of from 0.08 to
5 wt% based on the aerosolisable formulation. In one aspect the acid is
present in an
amount of no greater than 4 wt% based on the aerosolisable formulation. In one
aspect the
acid is present in an amount of from 0.01 to 4 wt% based on the aerosolisable
formulation.
In one aspect the acid is present in an amount of from 0.02 to 4 wt% based on
the
aerosolisable formulation. In one aspect the acid is present in an amount of
from 0.05 to 4
wt% based on the aerosolisable formulation. In one aspect the acid is present
in an amount
of from 0.08 to 4 wt% based on the aerosolisable formulation. In one aspect
the acid is
present in an amount of no greater than 3 wt% based on the aerosolisable
formulation. In
one aspect the acid is present in an amount of from 0.01 to 3 wt% based on the
aerosolisable formulation. In one aspect the acid is present in an amount of
from 0.02 to 3
wt% based on the aerosolisable formulation. In one aspect the acid is present
in an amount
of from 0.05 to 3 wt% based on the aerosolisable formulation. In one aspect
the acid is
present in an amount of from 0.08 to 3 wt% based on the aerosolisable
formulation. In one
aspect the acid is present in an amount of no greater than 2 wt% based on the
aerosolisable
formulation. In one aspect the acid is present in an amount of from 0.01 to 2
wt% based on
the aerosolisable formulation. In one aspect the acid is present in an amount
of from 0.02 to
2 wt% based on the aerosolisable formulation. In one aspect the acid is
present in an
amount of from 0.05 to 2 wt% based on the aerosolisable formulation. In one
aspect the acid
is present in an amount of from 0.08 to 2 wt% based on the aerosolisable
formulation. In one
aspect the acid is present in an amount of no greater than 1 wt% based on the
aerosolisable
formulation. In one aspect the acid is present in an amount of from 0.01 to 1
wt% based on
the aerosolisable formulation. In one aspect the acid is present in an amount
of from 0.02 to
1 wt% based on the aerosolisable formulation. In one aspect the acid is
present in an
amount of from 0.05 to 1 wt% based on the aerosolisable formulation. In one
aspect the acid
is present in an amount of from 0.08 to 1 wt% based on the aerosolisable
formulation. In one
aspect the acid is present in an amount of from 0.1 to 1 wt% based on the
aerosolisable
formulation. In one aspect the acid is present in an amount of no greater than
0.6 wt% based
on the aerosolisable formulation. In one aspect the acid is present in an
amount of from 0.01
to 0.6 wt% based on the aerosolisable formulation. In one aspect the acid is
present in an
amount of from 0.02 to 0.6 wt% based on the aerosolisable formulation. In one
aspect the
acid is present in an amount of from 0.05 to 0.6 wt% based on the
aerosolisable formulation.
13
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
In one aspect the acid is present in an amount of from 0.08 to 0.6 wt% based
on the
aerosolisable formulation. In one aspect the acid is present in an amount of
from 0.1 to 0.6
wt% based on the aerosolisable formulation. In one aspect the acid is present
in an amount
of no greater than 0.5 wt% based on the aerosolisable formulation. In one
aspect the acid is
present in an amount of from 0.01 to 0.5 wt% based on the aerosolisable
formulation. In one
aspect the acid is present in an amount of from 0.02 to 0.5 wt% based on the
aerosolisable
formulation. In one aspect the acid is present in an amount of from 0.05 to
0.5 wt% based on
the aerosolisable formulation. In one aspect the acid is present in an amount
of from 0.08 to
0.5 wt% based on the aerosolisable formulation. In one aspect the acid is
present in an
amount of no greater than 0.2 wt% based on the aerosolisable formulation. In
one aspect the
acid is present in an amount of from 0.01 to 0.2 wt% based on the
aerosolisable formulation.
In one aspect the acid is present in an amount of from 0.02 to 0.2 wt% based
on the
aerosolisable formulation. In one aspect the acid is present in an amount of
from 0.05 to 0.2
wt% based on the aerosolisable formulation. In one aspect the acid is present
in an amount
of from 0.08 to 0.2 wt% based on the aerosolisable formulation. In one aspect
the acid is
present in an amount of no greater than 0.1 wt% based on the aerosolisable
formulation. In
one aspect the acid is present in an amount of from 0.01 to 0.1 wt% based on
the
aerosolisable formulation. In one aspect the acid is present in an amount of
from 0.02 to 0.1
wt% based on the aerosolisable formulation. In one aspect the acid is present
in an amount
of from 0.05 to 0.1 wt% based on the aerosolisable formulation. In one aspect
the acid is
present in an amount of from 0.08 to 0.1 wt% based on the aerosolisable
formulation.
In one aspect the acid has a solubility in water of at least 2g/L at 20 C. In
one aspect the
acid has a solubility in water of at least 5g/L at 20 C. In one aspect the
acid has a solubility
in water of at least 10g/L at 20 C. In one aspect the acid has a solubility
in water of at least
20g/L at 20 C. In one aspect the acid has a solubility in water of at least
50g/L at 20 C. In
one aspect the acid has a solubility in water of at least 100g/L at 20 C. In
one aspect the
acid has a solubility in water of at least 200g/L at 20 C. In one aspect the
acid has a
solubility in water of at least 300g/L at 20 C. In one aspect the acid has a
solubility in water
of at least 400g/L at 20 C. In one aspect the acid has a solubility in water
of at least 500g/L
at 20 C. In one aspect the acid has a solubility in water of at least 600g/L
at 20 C. In one
aspect the acid has a solubility in water of at least 700g/L at 20 C. In one
aspect the acid
has a solubility in water of at least 800g/L at 20 C. In one aspect the acid
has a solubility in
water of at least 900g/L at 20 C. In one aspect the acid has a solubility in
water of at least
1000g/L at 20 C. In one aspect the acid has a solubility in water of at least
1100g/L at 20 C.
The amount of acid and the solubility of the acid may be selected such that a
given amount
14
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
of the acid will dissolve in the water. In one aspect at 20 C at least 20% of
the acid
dissolves in the water. In one aspect at 25 C at least 20% of the acid
dissolves in the water.
In one aspect at 30 C at least 20% of the acid dissolves in the water. In one
aspect at 20 C
at least 35% of the acid dissolves in the water. In one aspect at 20 C at
least 40% of the
acid dissolves in the water. In one aspect at 20 C at least 45% of the acid
dissolves in the
water. In one aspect at 20 C at least 50% of the acid dissolves in the water.
In one aspect
at 20 C at least 55% of the acid dissolves in the water.
In the aspects of the invention that nicotine is present, the molar ratio of
acid to nicotine may
be selected as desired. In one aspect the molar ratio of acid to nicotine is
from 5:1 to 1:5. In
one aspect the molar ratio of acid to nicotine is from 4:1 to 1:4. In one
aspect the molar ratio
of acid to nicotine is from 3:1 to 1:3. In one aspect the molar ratio of acid
to nicotine is from
2:1 to 1:2. In one aspect the molar ratio of acid to nicotine is from 1.5:1 to
1:1.5. In one
aspect the molar ratio of acid to nicotine is from 1.2:1 to 1:1.2. In one
aspect the molar ratio
of acid to nicotine is from 5:1 to 1:1. In one aspect the molar ratio of acid
to nicotine is from
4:1 to 1:1. In one aspect the molar ratio of acid to nicotine is from 3:1 to
1:1. In one aspect
the molar ratio of acid to nicotine is from 2:1 to 1:1. In one aspect the
molar ratio of acid to
nicotine is from 1.5:1 to 1:1. In one aspect the molar ratio of acid to
nicotine is from 1.2:1 to
1:1.
In one aspect the total content of acid present in the formulation is no
greater than 5 mole
equivalents based on the nicotine. In one aspect the total content of acid
present in the
formulation is no greater than 4 mole equivalents based on the nicotine. In
one aspect the
total content of acid present in the formulation is no greater than 3 mole
equivalents based
on the nicotine. In one aspect the total content of acid present in the
formulation is no
greater than 2 mole equivalents based on the nicotine. In one aspect the total
content of acid
present in the formulation is no greater than 1 mole equivalents based on the
nicotine.
In one aspect the total content of acid present in the formulation is no less
than 0.01 mole
equivalents based on the nicotine. In one aspect the total content of acid
present in the
formulation is no less than 0.05 mole equivalents based on the nicotine. In
one aspect the
total content of acid present in the formulation is no less than 0.1 mole
equivalents based on
the nicotine. In one aspect the total content of acid present in the
formulation is no less than
0.2 mole equivalents based on the nicotine. In one aspect the total content of
acid present in
the formulation is no less than 0.3 mole equivalents based on the nicotine. In
one aspect the
total content of acid present in the formulation is no less than 0.4 mole
equivalents based on
the nicotine. In one aspect the total content of acid present in the
formulation is no less than
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
0.5 mole equivalents based on the nicotine. In one aspect the total content of
acid present in
the formulation is no less than 0.7 mole equivalents based on the nicotine.
Flavour
As discussed herein, the aerosolisable formulation may comprise one or more
flavours or
flavouring components. As used herein, the terms "flavour" and "flavourant"
refer to
materials which, where local regulations permit, may be used to create a
desired taste or
aroma in a product for adult consumers. They may include extracts (e.g.
liquorice,
hydrangea, Japanese white bark magnolia leaf, chamomile, fenugreek, clove,
menthol,
Japanese mint, aniseed, cinnamon, herb, wintergreen, cherry, berry, peach,
apple,
Drambuie, bourbon, scotch, whiskey, spearmint, peppermint, lavender, cardamom,
celery,
cascarilla, nutmeg, sandalwood, bergamot, geranium, honey essence, rose oil,
vanilla,
lemon oil, orange oil, cassia, caraway, cognac, jasmine, ylang-ylang, sage,
fennel, piment,
ginger, anise, coriander, coffee, or a mint oil from any species of the genus
Mentha), flavour
enhancers, bitterness receptor site blockers, sensorial receptor site
activators or stimulators,
sugars and/or sugar substitutes (e.g., sucralose, acesulfame potassium,
aspartame,
saccharine, cyclamates, lactose, sucrose, glucose, fructose, sorbitol, or
mannitol), and other
additives such as charcoal, chlorophyll, minerals, botanicals, or breath
freshening agents.
They may be imitation, synthetic or natural ingredients or blends thereof.
They may be in any
suitable form, for example, oil, liquid, or powder. The one or more flavours
may be selected
from the group consisting of (4-(para-)methoxyphenyI)-2-butanone, vanillin, y-
undecalactone, menthone, 5-propenyl guaethol, menthol, para-mentha-8-thioI-3-
one and
mixtures thereof. In one aspect the flavour is at least menthol.
If present, the one or more flavours may be present in any suitable amount. In
one aspect
the one or more flavours are present in a total amount of no greater than 10
wt.% based on
the aerosolisable formulation. In one aspect the one or more flavours are
present in a total
amount of no greater than 7 wt.% based on the aerosolisable formulation. In
one aspect the
one or more flavours are present in a total amount of no greater than 5 wt.%
based on the
aerosolisable formulation. In one aspect the one or more flavours are present
in a total
amount of no greater than 4 wt.% based on the aerosolisable formulation. In
one aspect the
one or more flavours are present in a total amount of no greater than 3 wt.%
based on the
aerosolisable formulation. In one aspect the one or more flavours are present
in a total
amount of no greater than 2wt.cY0 based on the aerosolisable formulation. In
one aspect the
one or more flavours are present in a total amount of no greater than 1wt.c/o
based on the
aerosolisable formulation.
16
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
In one aspect the one or more flavours are present in a total amount of from
0.01 to 5wt.c/o
based on the aerosolisable formulation. In one aspect the one or more flavours
are present
in a total amount of from 0.01 to 4wt.c/o based on the aerosolisable
formulation. In one
aspect the one or more flavours are present in a total amount of from 0.01 to
3wt.cY0 based
on the aerosolisable formulation. In one aspect the one or more flavours are
present in a
total amount of from 0.01 to 2wt.c/o based on the aerosolisable formulation.
In one aspect the
one or more flavours are present in a total amount of from 0.01 to 1wt.c/o
based on the
aerosolisable formulation. In one aspect the one or more flavours are present
in a total
.. amount of from 0.01 to 0.5wt.% based on the aerosolisable formulation.
Formulation
In one aspect, if the aerosolisable formulation contains one or more
cyclodextrins, then the
aerosolisable formulation contains no flavours that can be encapsulated by the
one or more
cyclodextrins. In one aspect, if the aerosolisable formulation contains one or
more
cyclodextrins, then the aerosolisable formulation contains no flavours.
As will be appreciated, one or more cyclodextrins may or may not be present in
any suitable
amount in the aerosolisable formulation. In one aspect the one or more
cyclodextrins are
present in a total amount of no greater than 12 wt.% based on the
aerosolisable formulation.
In one aspect the one or more cyclodextrins are present in a total amount of
no greater than
10 wt.% based on the aerosolisable formulation. In one aspect the one or more
cyclodextrins
are present in a total amount of no greater than 9 wt.% based on the
aerosolisable
formulation. In one aspect the one or more cyclodextrins are present in a
total amount of no
greater than 8 wt.% based on the aerosolisable formulation. In one aspect the
one or more
cyclodextrins are present in a total amount of no greater than 7 wt.% based on
the
aerosolisable formulation. In one aspect the one or more cyclodextrins are
present in a total
amount of no greater than 6 wt.% based on the aerosolisable formulation. In
one aspect the
one or more cyclodextrins are present in a total amount of no greater than 5
wt.% based on
the aerosolisable formulation. In one aspect the one or more cyclodextrins are
present in a
total amount of no greater than 4 wt.% based on the aerosolisable formulation.
In one aspect
the one or more cyclodextrins are present in a total amount of no greater than
3 wt.% based
on the aerosolisable formulation. In one aspect the one or more cyclodextrins
are present in
a total amount of no greater than 2 wt.% based on the aerosolisable
formulation. In one
aspect the one or more cyclodextrins are present in a total amount of no
greater than 1 wt.%
based on the aerosolisable formulation. In one aspect the one or more
cyclodextrins are
17
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
present in a total amount of no greater than 0.1 wt.% based on the
aerosolisable formulation.
In one aspect the one or more cyclodextrins are present in a total amount of
no greater than
0.01 wt.% based on the aerosolisable formulation. In one aspect the one or
more
cyclodextrins are present in a total amount of no greater than 0.001 wt.%
based on the
aerosolisable formulation.
The one or more cyclodextrins may be selected from the group consisting of
unsubstituted
cyclodextrins, substituted cyclodextrins and mixtures thereof. In one aspect
at least one
cyclodextrin is an unsubstituted cyclodextrin. In one aspect the one or more
cyclodextrins
are selected from the group consisting of unsubstituted cyclodextrins. In one
aspect at least
one cyclodextrin is a substituted cyclodextrin. In one aspect the one or more
cyclodextrins
are selected from the group consisting of substituted cyclodextrins.
In one aspect the one or more cyclodextrins are selected from the group
consisting of
unsubstituted (a)-cyclodextrin, substituted (a)-cyclodextrin, unsubstituted
(p)-cyclodextrin,
substituted (p)-cyclodextrin, unsubstituted (y)-cyclodextrin, substituted (y)-
cyclodextrin, and
mixtures thereof. In one aspect the one or more cyclodextrins are selected
from the group
consisting of unsubstituted (p)-cyclodextrin, substituted (3)-cyclodextrin,
and mixtures
thereof.
In one aspect the one or more cyclodextrins are selected from the group
consisting of
unsubstituted (a)-cyclodextrin, unsubstituted (p)-cyclodextrin, unsubstituted
(y)-cyclodextrin,
and mixtures thereof. In one aspect the one or more cyclodextrins is selected
from
unsubstituted (3)-cyclodextrin.
In one aspect the one or more cyclodextrins are selected from the group
consisting of
substituted (a)-cyclodextrin, substituted (p)-cyclodextrin, substituted (y)-
cyclodextrin, and
mixtures thereof. In one aspect the one or more cyclodextrins is selected from
substituted
(p)-cyclodextrins. Chemical substitutions at the 2-, 3-, and 6-hydroxyl sites
are envisaged,
and in particular substitution at the 2-position.
In one aspect the one or more cyclodextrins are selected from the group
consisting of 2-
hyd roxy- propyl-a-cyclodextrin, 2-hydroxy-propyl-3-cyclodextrin,
2-hydroxy-propyl-y-
cyclodextrin and mixtures thereof. In one aspect the one or more cyclodextrins
is at least 2-
hydroxy-propyl-a-cyclodextrin. In one aspect the one or more cyclodextrins is
at least 2-
hydroxy-propyl-3-cyclodextrin. In one aspect the one or more cyclodextrins is
at least 2-
18
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
hydroxy-propyl-y-cyclodextrin.
2-hydroxy-propyl derivatives of cyclodextrins, such as 2-hydroxy-propyl-3-
cyclodextrin have
increased solubility in water when compared to base cyclodextrins such as p-
cyclodextrin.
In further aspects, the aerosolisable formulation contains cyclodextrins in a
total amount of
no greater than 0.001 wt.% based on the aerosolisable formulation, such as
cyclodextrins in
a total amount of no greater than 1x10-4 wt.% based on the aerosolisable
formulation, such
as cyclodextrins in a total amount of no greater than 1x10-5 wt.% based on the
aerosolisable
formulation, such as cyclodextrins in a total amount of no greater than 1x10-6
wt.% based on
the aerosolisable formulation. Thus in further aspects, the present invention
provides
(1) an aerosolisable formulation comprising
(i) water in an amount of at least 50 wt.% based on the aerosolisable
formulation; and
(ii) nicotine;
wherein the nicotine is present in an amount of no greater than 1wt.cY0 based
on the
aerosolisable formulation; and
wherein cyclodextrins are present in a total amount of from 0 to 0.001 wt.%
based on the
aerosolisable formulation.
(2) a process for forming an aerosol, the process comprising aerosolising an
aerosolisable
formulation comprising
(i) water in an amount of at least 50 wt.% based on the aerosolisable
formulation; and
(ii) nicotine;
wherein the nicotine is present in an amount of no greater than 1wt.c/o based
on the
aerosolisable formulation; and
wherein cyclodextrins are present in a total amount of from 0 to 0.001 wt.%
based on the
aerosolisable formulation.
(3) a contained aerosolisable formulation comprising
(a) a container; and
(b) an aerosolisable formulation, comprising
(i) water in an amount of at least 50 wt.% based on the aerosolisable
formulation;
and
(ii) nicotine;
wherein the nicotine is present in an amount of no greater than 1wt.c/o based
on the
aerosolisable formulation; and
wherein cyclodextrins are present in a total amount of from 0 to 0.001 wt.%
based on
the aerosolisable formulation.
(4) an electronic aerosol provision system comprising:
19
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
(a) an aerosoliser for aerosolising formulation for inhalation by a user of
the electronic
aerosol provision system;
(b) a power supply comprising a cell or battery for supplying power to the
aerosoliser
(c) an aerosolisable formulation , comprising
(i) water in an amount of at least 50 wt.% based on the aerosolisable
formulation;
and
(ii) nicotine;
wherein the nicotine is present in an amount of no greater than 1wt.c/o based
on the
aerosolisable formulation; and
wherein cyclodextrins are present in a total amount of from 0 to 0.001 wt.%
based on
the aerosolisable formulation.
Process
As discussed herein, in one aspect there is provided a process for forming an
aerosol, the
process comprising aerosolising an aerosolisable formulation comprising
(i) water in an amount of at least 50 wt.% based on the aerosolisable
formulation; and
(ii) nicotine;
wherein the nicotine is present in an amount of no greater than 1wt.c/o based
on the
aerosolisable formulation.
In the process the aerosol may be formed by a process performed at a
temperature below
60 C.In the process the aerosol may be formed by a process performed at a
temperature
below 50 C. In the process the aerosol may be formed by a process performed at
a
temperature below 40 C. In the process the aerosol may be formed by a process
performed
at a temperature below 30 C. In the process the aerosol may be formed by a
process
performed at a temperature below 25 C. In the process the aerosol may be
formed by a
process which does not involve heating.
In the process the aerosol may be formed by applying ultrasonic energy to the
aerosolisable
formulation.
In one aspect the aerosol has a D50 of from 2 to 6pm. References in the
present
specification to particle size distribution, D50, D10 or D90 refer to values
measured in
accordance with British and European Pharmacopoeia, 2.9.31 Particle Size
Analysis By
Laser Light Diffraction (see BRITISH PHARMACOPOEIA COMMISSION. (2014), British
Pharmacopoeia. London, England: Stationery Office and COUNCIL OF EUROPE.
(2013).
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
European Pharmacopoeia. Strasbourg, France: Council of Europe). The terms D50,
Dv50
and Dx50 are interchangeable. The terms D10, Dv10 and Dx10 are
interchangeable. The
terms D90, Dv90 and Dx90 are interchangeable.
In one aspect the aerosol has a D50 of from 2.5 to 6pm. In one aspect the
aerosol has a
D50 of from 3 to 6pm. In one aspect the aerosol has a D50 of from 3.5 to 6pm.
In one aspect
the aerosol has a D50 of from 4 to 6pm. In one aspect the aerosol has a D50 of
from 4.5 to
6pm. In one aspect the aerosol has a D50 of from 5 to 6pm. In one aspect the
aerosol has a
D50 of from 2.5 to 5.5pm. In one aspect the aerosol has a D50 of from 3 to
5.5pm. In one
aspect the aerosol has a D50 of from 3.5 to 5.5pm. In one aspect the aerosol
has a D50 of
from 4 to 5.5pm. In one aspect the aerosol has a D50 of from 4.5 to 5.5pm. In
one aspect
the aerosol has a D50 of from 5 to 5.5pm.
In one aspect the aerosol has a D10 of at least 0.5pm. In one aspect the
aerosol has a D10
of at least 1pm. In one aspect the aerosol has a D10 of at least 2pm.
In one aspect the aerosol has a D90 of no greater than 15pm. In one aspect the
aerosol has
a D90 of no greater than 12pm. In one aspect the aerosol has a D90 of no
greater than
lOpm.
In one aspect D50 is measured after exclusion of particles having a particle
size of less than
1pm. In one aspect D10 is measured after exclusion of particles having a
particle size of less
than 1pm. In one aspect D90 is measured after exclusion of particles having a
particle size
of less than 1pm.
The formulation may be contained or delivered by any means. In one aspect the
present
invention provides a contained aerosolisable formulation comprising (a) one or
more
containers; and (b) an aerosolisable formulation as defined herein. The
container may be
any suitable container, for example to allow for the storage or delivery of
the formulation. In
one aspect the container is configured for engagement with an electronic
aerosol provision
system. The container may be configured to become fluidly in communication
with an
electronic aerosol provision system so that formulation may be delivered to
the electronic
aerosol provision system. As described above, the present disclosure relates
to container
which may be used in an electronic aerosol provision system, such as an e-
cigarette.
Throughout the following description the term "e-cigarette" is used; however,
this term may
be used interchangeably with electronic aerosol provision system.
21
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
As discussed herein, the container of the present invention is typically
provided for the
delivery of aerosolisable formulation to or within an e-cigarette. The
aerosolisable
formulation may be held within an e-cigarette or may be sold as a separate
container for
subsequent use with or in an e-cigarette. As understood by one skilled in the
art, e-cigarettes
may contain a unit known as a detachable cartomiser which typically comprises
a reservoir
of aerosolisable formulation, a wick material and a heating element for
vaporising the
aerosolisable formulation. In some e-cigarettes, the cartomiser is part of a
single-piece
device and is not detachable. In one aspect the container is a cartomiser or
is part of a
cartomiser. In one aspect the container is not a cartomiser or part of a
cartomiser and is a
container, such as a tank, which may be used to deliver nicotine formulation
to or within an
e-cigarette.
In one aspect the container is part of an e-cigarette. Therefore in a further
aspect the present
invention provides an electronic aerosol provision system comprising: an
aerosolisable
formulation as defined herein; an aerosoliser for aerosolising formulation for
inhalation by a
user of the electronic aerosol provision system; and a power supply comprising
a cell or
battery for supplying power to the aerosoliser.
The process of the present invention may comprises additional steps either
before the steps
listed, after the steps listed or between one or more of the steps listed.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will now be described in further detail by way of
example only with
.. reference to the accompanying figures in which:-
Figure 1 shows a graph illustrating variation of psKa2 with nicotine
concentration; and
Figure 2 shows the nicotine hit, irritation and impact rating of Mojito
formulation.
The invention will now be described with reference to the following non-
limiting example.
Examples
Example 1
A series of tests were conducted using commercially available vibrating mesh
nebuliser
devices. The "nicotine free" device was loaded with formulation containing
88.0% (w/w)
water, 6.0% propylene glycol containing vanilla flavour, and 6.0 glycerol.
22
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
A similar device was prepared wherein 1.2% w/w nicotine was added to the
formulation, with
the water content was commensurately reduced to 86.8% (w/w).
A similar device was prepared wherein 0.6% w/w nicotine was added to the
formulation, with
the water content was commensurately adjusted to 87.4% (w/w).
A similar device was prepared wherein 0.3% w/w nicotine was added to the
formulation, with
the water content was commensurately adjusted to 87.7% (w/w).
A similar device was prepared wherein 0.1% w/w nicotine was added to the
formulation, with
the water content was commensurately adjusted to 87.9% (w/w).
One each of these devices was presented to 8 panellists comprising e-cigarette
users, and
the panellists were asked to puff on the devices in a sequential monadic
fashion for 5 puffs
on each device. They were asked to identify the preferred nicotine strength
from the four
offered to them.
8 panellists preferred a nicotine strength below 1.2% (w/w), 7 people
preferred a nicotine
strength below 0.6% (w/w), and 5 people preferred a nicotine strength below
0.3% (w/w).
Example 2
Three flavoured formulations with different water ratios and nicotine content
were assessed
by up to 10 panellists, which are experienced vapers with different nicotine
tolerances.
A series of tests were conducted using commercially available vibrating mesh
nebuliser
devices. The device was loaded with formulation containing 97.2% (w/w) water,
2.0% (w/w)
propylene glycol containing amaretto flavour, and 0.8% (w/w) nicotine.
A similar device was prepared wherein 0.9% (w/w) nicotine was added to the
formulation,
with the water content was commensurately reduced to 97.1% (w/w).
A similar device was prepared wherein 1.1% (w/w) nicotine was added to the
formulation,
with the water content was commensurately reduced to 96.9% (w/w).
23
CA 03118060 2021-04-28
WO 2020/089640
PCT/GB2019/053095
The summary of tested formulations and their properties are presented in the
table below.
Panellists were asked to evaluate the formulations in a randomised manner.
During the
sensory evaluation the panellists ranked several sensory attributes such as
throat irritation
and chest impact from low (1) to high (9). The panellists were also asked to
indicate the
most favourite formulation among the tested.
Formulation Water, Nicotine, (P)-Cyclodextrin Ng panellists
(w/w) % (w/w) %
Amaretto 97.2 0.8 absent 10
Amaretto 97.1 0.9 absent 10
Amaretto 96.9 1.1 absent 10
4 out of 10 panellists preferred Amaretto with 0.8 % (w/w) nicotine strength,
3 out of 10
panellists preferred Amaretto with 0.9% (w/w) nicotine strength, 2 out of 10
panellists which
were high nicotine users preferred Amaretto with 1.1 % (w/w) nicotine
strength, and 1 out of
10 panellists did not like any of the formulations. Overall 7 out of 10
preferred Amaretto
formulation with <1% (w/w) nicotine.
Further formulations were prepared also containing (3)-cyclodextrin and were
tested by 6
panellists in the same manner as the Amaretto formulation.
The device was loaded with formulation containing 73.4% (w/w) water, 10.0%
(w/w) 2-
hydroxy-propyl-3-cyclodextrin, 13% (w/w) glycerol 2.0% (w/w) propylene glycol
containing
mojito flavour, 0.8% (w/w) nicotine and 0.8% (w/w) benzoic acid.
.. A similar device was prepared wherein 0.9% (w/w) nicotine was added to the
formulation,
with the water content was commensurately reduced to 73.2% (w/w).
A similar device was prepared wherein 1.1% (w/w) nicotine was added to the
formulation,
with the water content was commensurately reduced to 72.8% (w/w).
The summary of tested formulations and their properties are presented in the
table below.
Formulation Water, Nicotine, (P)-Cyclodextrin Ng panellists
(w/w) % (w/w) %
Mojito 73.4 0.8 present 6
Mojito 73.2 0.9 present 6
24
CA 03118060 2021-04-28
WO 2020/089640 PCT/GB2019/053095
Mojito 72.8 1.1 present 6
4 out of 6 panellists preferred Mojito with 0.8% (w/w) nicotine strength, 1
out of 6 panellists
preferred Mojito with 1.1 % (w/w) nicotine strength and 1 out of 6 panellists
did not like any
of the formulations. Overall 4 out of 6 preferred Mojito formulation with <1%
nicotine.
Nicotine hit, irritation and impact were rated and are shown in Figure 2. As
can be seen from
Figure 2 Mojito with 1.1 (w/w) % nicotine formulation was rated the highest
for nicotine hit,
irritation and impact.
Various modifications and variations of the present invention will be apparent
to those skilled
in the art without departing from the scope and spirit of the invention.
Although the invention
has been described in connection with specific preferred embodiments, it
should be
understood that the invention as claimed should not be unduly limited to such
specific
embodiments. Indeed, various modifications of the described modes for carrying
out the
invention which are obvious to those skilled in chemistry or related fields
are intended to be
within the scope of the following claims.
