U.S. patent application number 17/290319 was filed with the patent office on 2021-12-16 for aerosolisable formulation.
The applicant listed for this patent is NICOVENTURES TRADING LIMITED. Invention is credited to Ross CABOT.
Application Number | 20210386110 17/290319 |
Document ID | / |
Family ID | 1000005865004 |
Filed Date | 2021-12-16 |
United States Patent
Application |
20210386110 |
Kind Code |
A1 |
CABOT; Ross |
December 16, 2021 |
AEROSOLISABLE FORMULATION
Abstract
An aerosolized formulation comprising (i) water in an amount of
at least 85 wt. % based on the aerosolizable formulation; and (ii)
nicotine. A process for forming an aerosol, the process comprising
aerosolizing an aerosolizable formulation comprising (i) water in
an amount of at least 85 wt. % based on the aerosolizable
formulation; and (ii) nicotine or one or more flavors. A contained
aerosolizable formulation in a container, and an electronic aerosol
provision system having an aerosolizer for aerosolizing the
aerosolizable formulation for inhalation by a user.
Inventors: |
CABOT; Ross; (London,
GB) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NICOVENTURES TRADING LIMITED |
London |
|
GB |
|
|
Family ID: |
1000005865004 |
Appl. No.: |
17/290319 |
Filed: |
October 31, 2019 |
PCT Filed: |
October 31, 2019 |
PCT NO: |
PCT/GB2019/053092 |
371 Date: |
April 30, 2021 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A24F 40/05 20200101;
A24F 40/10 20200101; A24B 15/167 20161101 |
International
Class: |
A24B 15/167 20060101
A24B015/167; A24F 40/05 20060101 A24F040/05; A24F 40/10 20060101
A24F040/10 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 1, 2018 |
GB |
1817865.7 |
Claims
1. An aerosolizable formulation comprising: (i) water in an amount
of at least 85 wt. % based on the aerosolizable formulation; and
(ii) nicotine.
2. An aerosolizable formulation according to claim wherein water is
present in an amount of at least 90 wt. % based on the
aerosolizable formulation.
3. An aerosolizable formulation according to claim wherein water is
present in an amount of at least 95 wt. % based on the
aerosolizable formulation.
4. An aerosolizable formulation according to claim 1, wherein water
is present in an amount of at least 95 wt. % based on the
aerosolizable formulation.
5. An aerosolizable formulation according to claim 1, wherein water
is present in an amount of at least 99 wt. % based on the
aerosolizable formulation.
6. An aerosolizable formulation according to claim 1, wherein the
nicotine is present in an amount of no greater than 1 wt. % based
on the aerosolizable formulation.
7. An aerosolizable formulation according to claim 1, wherein the
nicotine is present in an amount of from 0.01 to 0.6 wt. % based on
the aerosolizable formulation.
8. An aerosolizable formulation according to claim 1, wherein the
aerosolizable formulation further comprises an acid.
9. An aerosolizable formulation according to claim 8, wherein 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.
10. An aerosolizable formulation according to claim 8, wherein the
acid is selected from the group consisting of citric acid, benzoic
acid, levulinic acid, sorbic acid, lactic acid, and mixtures
thereof.
11. An aerosolizable formulation according to claim 8, wherein the
acid comprises is citric acid.
12. An aerosolizable formulation according to claim 8, wherein a
total content of acid present in the formulation is no greater than
1 mole equivalents based on the nicotine.
13. An aerosolizable formulation according to claim 8, wherein a
total content of acid present in the solution is no less than 0.1
mole equivalents based on the nicotine.
14. An aerosolizable formulation according to claim 1, further
comprising one or more flavors.
15. An aerosolizable formulation according to claim 14, wherein the
one or more flavors is selected from the group consisting of
(4-(para-) methoxyphenyl)-2-butanone, vanillin,
.gamma.-undecalactone, menthone, 5-propenyl guaethol, menthol,
para-mentha-8-thiol-3-one and mixtures thereof.
16. An aerosolizable formulation according to claim 14, wherein the
one or more flavors comprises menthol.
17. An aerosolizable formulation according to claim 14, wherein the
one or more flavors is flavours are present in a total amount of no
greater than 2 wt. % based on the aerosolizable formulation.
18. An aerosolizable formulation according to claim 14, wherein the
one or more flavors is present in a total amount of from 0.01 to 1
wt. % based on the aerosolizable formulation.
19. An aerosolizable formulation according to claim 1, further
comprising one or more cyclodextrins, wherein the aerosolizable
formulation contains no flavors that can be encapsulated by the one
or more cyclodextrins
20. An aerosolizable formulation according to claim 1, further
comprising one or more cyclodextrins, wherein the aerosolizable
formulation contains no flavors.
21. A process for forming an aerosol, the process comprising:
aerosolising an aerosolizable formulation, the aerosolizable
formulation comprising: (i) water in an amount of at least 85 wt. %
based on the aerosolizable formulation; and (ii) nicotine or one or
more flavors.
22. A process according to claim 21, wherein the aerosolizable
formulation comprises nicotine and, optionally, one or more
flavors.
23. (canceled)
24. A process according to claim 21, wherein the aerosolizable
formulation is aerosolized to form the aerosol at a temperature
below 50.degree. C.
25. A process according to claim 21, wherein aerosolizing the
aerosolizable formulation comprises applying ultrasonic energy to
the aerosolizable formulation.
26. A contained aerosolizable formulation comprising: (a) a
container; and (b) an aerosolizable formulation, the aerosolizable
formulation comprising: (i) water in an amount of at least 85 wt. %
based on the aerosolizable formulation; and (ii) nicotine.
27. (canceled)
28. A contained aerosolizable formulation according to claim 26,
wherein the container is configured for engagement with an
electronic aerosol provision system.
29. An electronic aerosol provision system comprising: (a) an
aerosolizer for aerosolizing an aerosolizable 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 aerosolizer; and (c) the aerosolizable formulation,
comprising: (i) water in an amount of at least 85 wt. % based on
the aerosolizable formulation; and (ii) nicotine or one or more
flavors.
30. An electronic aerosol provision system according to claim 29,
wherein the aerosolizable formulation comprises nicotine and,
optionally, one or more flavors.
31. (canceled)
Description
PRIORITY CLAIM
[0001] The present application is a National Phase entry of PCT
Application No. PCT/GB2019/053092, filed Oct. 31, 2019 which claims
priority from GB Patent Application No. 1817865.7 filed Nov. 1,
2018, each of which is hereby fully incorporated herein by
reference.
FIELD OF THE INVENTION
[0002] The present disclosure relates to an aerosolizable
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
[0003] Electronic aerosol provision systems such as e-cigarettes
generally contain a reservoir of liquid which is to be vaporized,
typically containing nicotine. When a user inhales on the device, a
heater is activated to vaporize a small amount of liquid, which is
therefore inhaled by the user.
[0004] 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.
[0005] 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 flavor 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 flavor, 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
vapor 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.
[0006] 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
[0007] In one aspect there is provided an aerosolizable formulation
comprising
[0008] (i) water in an amount of at least 85 wt. % based on the
aerosolizable formulation; and
[0009] (ii) nicotine. In this aspect, if the aerosolizable
formulation contains one or more cyclodextrins, then the
aerosolizable formulation may contain no flavors that can be
encapsulated by the one or more cyclodextrins.
[0010] In one aspect there is provided an aerosolizable formulation
comprising
[0011] (i) water in an amount of at least 95 wt. % based on the
aerosolizable formulation; and
[0012] (ii) nicotine.
[0013] In one aspect there is provided a process for forming an
aerosol, the process comprising aerosolizing an aerosolizable
formulation comprising
[0014] (i) water in an amount of at least 85 wt. % based on the
aerosolizable formulation; and
[0015] (ii) nicotine or one or more flavors. In this aspect, if the
aerosolizable formulation contains one or more cyclodextrins, then
the aerosolizable formulation may contain no flavors that can be
encapsulated by the one or more cyclodextrins.
[0016] In one aspect there is provided a process for forming an
aerosol, the process comprising aerosolizing an aerosolizable
formulation comprising
[0017] (i) water in an amount of at least 95 wt. % based on the
aerosolizable formulation; and
[0018] (ii) nicotine.
[0019] In one aspect there is provided a contained aerosolizable
formulation comprising (a) a container; and (b) an aerosolizable
formulation, comprising (i) water in an amount of at least 85 wt. %
based on the aerosolizable formulation; and (ii) nicotine. In this
aspect, if the aerosolizable formulation contains one or more
cyclodextrins, then the aerosolizable formulation may contain no
flavors that can be encapsulated by the one or more
cyclodextrins.
[0020] In one aspect there is provided a contained aerosolizable
formulation comprising
[0021] (a) a container; and
[0022] (b) an aerosolizable formulation, comprising [0023] (i)
water in an amount of at least 95 wt. % based on the aerosolizable
formulation; and [0024] (ii) nicotine.
[0025] In one aspect there is provided an electronic aerosol
provision system comprising: (a) an aerosolizer for aerosolizing
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 aerosolizer (c) an aerosolizable
formulation, comprising (i) water in an amount of at least 85 wt. %
based on the aerosolizable formulation; and (ii) nicotine or one or
more flavors. In this aspect, if the aerosolizable formulation
contains one or more cyclodextrins, then the aerosolizable
formulation may contain no flavors that can be encapsulated by the
one or more cyclodextrins.
[0026] In one aspect there is provided an electronic aerosol
provision system comprising:
[0027] (a) an aerosolizer for aerosolizing formulation for
inhalation by a user of the electronic aerosol provision
system;
[0028] (b) a power supply comprising a cell or battery for
supplying power to the aerosolizer
[0029] (c) an aerosolizable formulation, comprising [0030] (i)
water in an amount of at least 95 wt. % based on the aerosolizable
formulation; and [0031] (ii) nicotine.
BRIEF DESCRIPTION OF THE DRAWINGS
[0032] The present disclosure will now be described in further
detail by way of example only with reference to the accompanying
FIGURE in which:
[0033] FIG. 1 shows a graph illustrating variation of
p.sub.sK.sub.a2 with nicotine concentration.
DETAILED DESCRIPTION
[0034] As discussed herein is provided an aerosolizable formulation
comprising (i) water in an amount of at least 85 wt. % based on the
aerosolizable formulation; and (ii) nicotine. There is further
provided a process for forming an aerosol, the process comprising
aerosolizing an aerosolizable formulation comprising
[0035] (i) water in an amount of at least 85 wt. % based on the
aerosolizable formulation; and
[0036] (ii) nicotine or one or more flavors.
[0037] We have found that an advantageous system may be provided in
which an aerosolizable formulation contains a very high content of
water and is used to deliver nicotine and/or flavor.
[0038] We have surprising found that the very high water content
provides a sensory perception for the user which is desirably close
to the nicotine `hit` and/or flavor release provided by tobacco
based cigarettes. This desirable nicotine `hit` and/or flavor
release is in contrast to `traditional` e-liquids based on glycerol
and propylene glycol which users sometimes do not use because of
the perceived differences in respect of nicotine `hit` and/or
flavor release provided by tobacco based cigarettes.
[0039] We have also identified that water-based system may be
provided in which aerosolized formulation is formed from an
aerosolizable 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
aerosolized 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 flavor
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.
[0040] For ease of reference, these and further aspects of the
present disclosure are now discussed under appropriate section
headings. However, the teachings under each section are not
necessarily limited to each particular section.
[0041] Water
[0042] As discussed herein the aerosolizable formulation comprises
water in an amount of at least 85 wt. % based on the aerosolizable
formulation. In one aspect water is present in an amount of at
least 87 wt. % based on the aerosolizable formulation. In one
aspect water is present in an amount of at least 89 wt. % based on
the aerosolizable formulation. In one aspect water is present in an
amount of at least 91 wt. % based on the aerosolizable formulation.
In one aspect water is present in an amount of at least 93 wt. %
based on the aerosolizable formulation. In one aspect water is
present in an amount of at least 95 wt. % based on the
aerosolizable formulation. In one aspect water is present in an
amount of at least 97 wt. % based on the aerosolizable formulation.
In one aspect water is present in an amount of at least 99 wt. %
based on the aerosolizable formulation. In one aspect water is
present in an amount of at least 99 wt. % based on the
aerosolizable formulation. In one aspect water is present in an
amount of at least 99.1 wt. % based on the aerosolizable
formulation. In one aspect water is present in an amount of at
least 99.2 wt. % based on the aerosolizable formulation. In one
aspect water is present in an amount of at least 99.3 wt. % based
on the aerosolizable formulation. In one aspect water is present in
an amount of at least 99.4 wt. % based on the aerosolizable
formulation. In one aspect water is present in an amount of at
least 99.5 wt. % based on the aerosolizable formulation. In one
aspect water is present in an amount of at least 99.6 wt. % based
on the aerosolizable formulation. In one aspect water is present in
an amount of at least 99.7 wt. % based on the aerosolizable
formulation. In one aspect water is present in an amount of at
least 99.8 wt. % based on the aerosolizable formulation. In one
aspect water is present in an amount of at least 99.9 wt. % based
on the aerosolizable formulation.
[0043] In one aspect water is present in an amount of from 85 to
99.9 wt. % based on the aerosolizable formulation. In one aspect
water is present in an amount of from 90 to 99.9 wt. % based on the
aerosolizable formulation. In one aspect water is present in an
amount of from 92 to 99.9 wt. % based on the aerosolizable
formulation. In one aspect water is present in an amount of from 94
to 99.9 wt. % based on the aerosolizable formulation. In one aspect
water is present in an amount of from 95 to 99.9 wt. % based on the
aerosolizable formulation. In one aspect water is present in an
amount of from 96 to 99.9 wt. % based on the aerosolizable
formulation. In one aspect water is present in an amount of from 97
to 99.9 wt. % based on the aerosolizable formulation. In one aspect
water is present in an amount of from 98 to 99.9 wt. % based on the
aerosolizable formulation. In one aspect water is present in an
amount of from 99 to 99.9 wt. % based on the aerosolizable
formulation.
[0044] 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 aerosolizable 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
aerosolizable formulation. In one aspect the aerosolizable
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 aerosolizable formulation. In one aspect the
aerosolizable formulation contains glycerol, propylene glycol,
1,3-propane diol and mixtures thereof in a combined amount of no
greater than 5 wt. % based on the aerosolizable formulation. In one
aspect the aerosolizable 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 aerosolizable formulation.
In one aspect the aerosolizable 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
aerosolizable formulation. In one aspect the aerosolizable
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 aerosolizable formulation. In one aspect the
aerosolizable 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 aerosolizable formulation. In
one aspect the aerosolizable 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
aerosolizable formulation. In one aspect the aerosolizable
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 aerosolizable formulation. In one aspect the
aerosolizable formulation contains no glycerol, propylene glycol,
1,3-propane diol and mixtures thereof.
[0045] In one aspect the aerosolizable formulation contains
glycerol, propylene glycol, and mixtures thereof in a combined
amount of no greater than 10 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
glycerol, propylene glycol, and mixtures thereof in a combined
amount of no greater than 8 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
glycerol, propylene glycol, and mixtures thereof in a combined
amount of no greater than 5 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
glycerol, propylene glycol, and mixtures thereof in a combined
amount of no greater than 2 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
glycerol, propylene glycol, and mixtures thereof in a combined
amount of no greater than 1 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
glycerol, propylene glycol, and mixtures thereof in a combined
amount of no greater than 0.5 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
glycerol, propylene glycol, and mixtures thereof in a combined
amount of no greater than 0.2 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
glycerol, propylene glycol, and mixtures thereof in a combined
amount of no greater than 0.1 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
glycerol, propylene glycol, and mixtures thereof in a combined
amount of no greater than 0.01 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
no glycerol, propylene glycol, and mixtures thereof.
[0046] In one aspect the aerosolizable formulation contains
glycerol in an amount of no greater than 10 wt. % based on the
aerosolizable formulation. In one aspect the aerosolizable
formulation contains glycerol in an amount of no greater than 8 wt.
% based on the aerosolizable formulation. In one aspect the
aerosolizable formulation contains glycerol in an amount of no
greater than 5 wt. % based on the aerosolizable formulation. In one
aspect the aerosolizable formulation contains glycerol in an amount
of no greater than 2 wt. % based on the aerosolizable formulation.
In one aspect the aerosolizable formulation contains glycerol in an
amount of no greater than 1 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
glycerol in an amount of no greater than 0.5 wt. % based on the
aerosolizable formulation. In one aspect the aerosolizable
formulation contains glycerol in an amount of no greater than 0.2
wt. % based on the aerosolizable formulation. In one aspect the
aerosolizable formulation contains glycerol in an amount of no
greater than 0.1 wt. % based on the aerosolizable formulation. In
one aspect the aerosolizable formulation contains glycerol in an
amount of no greater than 0.01 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
no glycerol.
[0047] In one aspect the aerosolizable formulation contains
propylene glycol in an amount of no greater than 10 wt. % based on
the aerosolizable formulation. In one aspect the aerosolizable
formulation contains propylene glycol in an amount of no greater
than 8 wt. % based on the aerosolizable formulation. In one aspect
the aerosolizable formulation contains propylene glycol in an
amount of no greater than 5 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
propylene glycol in an amount of no greater than 2 wt. % based on
the aerosolizable formulation. In one aspect the aerosolizable
formulation contains propylene glycol in an amount of no greater
than 1 wt. % based on the aerosolizable formulation. In one aspect
the aerosolizable formulation contains propylene glycol in an
amount of no greater than 0.5 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
propylene glycol in an amount of no greater than 0.2 wt. % based on
the aerosolizable formulation. In one aspect the aerosolizable
formulation contains propylene glycol in an amount of no greater
than 0.1 wt. % based on the aerosolizable formulation. In one
aspect the aerosolizable formulation contains propylene glycol in
an amount of no greater than 0.01 wt. % based on the aerosolizable
formulation. In one aspect the aerosolizable formulation contains
no propylene glycol.
[0048] Acid
[0049] In one aspect the aerosolizable 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.
[0050] 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.
[0051] 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.
[0052] 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 aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.01 to 6 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.02 to 6 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.05 to 6 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.08 to 6 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.01 to 5 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.02 to 5 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.05 to 5 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.08 to 5 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of no greater than 4 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.01 to 4 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.02 to 4 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.05 to 4 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.08 to 4 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of no greater than 3 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.01 to 3 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.02 to 3 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.05 to 3 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.08 to 3 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of no
greater than 2 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.01 to 2 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.02 to 2 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.05 to 2 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.08 to 2 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of no greater than 1 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.01 to 1 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.02 to 1 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.05 to 1 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.08 to 1 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.1 to 1 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of no greater than 0.6 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.01 to 0.6 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.02 to 0.6 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.05 to 0.6 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.08 to 0.6 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.1 to 0.6 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of no greater than 0.5 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.01 to 0.5 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.02 to 0.5 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.05 to 0.5 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.08 to 0.5 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of no greater than 0.2 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.01 to 0.2 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.02 to 0.2 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.05 to 0.2 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.08 to 0.2 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of no greater than 0.1 wt % based on the aerosolizable
formulation. In one aspect the acid is present in an amount of from
0.01 to 0.1 wt % based on the aerosolizable formulation. In one
aspect the acid is present in an amount of from 0.02 to 0.1 wt %
based on the aerosolizable formulation. In one aspect the acid is
present in an amount of from 0.05 to 0.1 wt % based on the
aerosolizable formulation. In one aspect the acid is present in an
amount of from 0.08 to 0.1 wt % based on the aerosolizable
formulation.
[0053] In one aspect the acid has a solubility in water of at least
2 g/L at 20.degree. C. In one aspect the acid has a solubility in
water of at least 5 g/L at 20.degree. C. In one aspect the acid has
a solubility in water of at least 10 g/L at 20.degree. C. In one
aspect the acid has a solubility in water of at least 20 g/L at
20.degree. C. In one aspect the acid has a solubility in water of
at least 50 g/L at 20.degree. C. In one aspect the acid has a
solubility in water of at least 100 g/L at 20.degree. C. In one
aspect the acid has a solubility in water of at least 200 g/L at
20.degree. C. In one aspect the acid has a solubility in water of
at least 300 g/L at 20.degree. C. In one aspect the acid has a
solubility in water of at least 400 g/L at 20.degree. C. In one
aspect the acid has a solubility in water of at least 500 g/L at
20.degree. C. In one aspect the acid has a solubility in water of
at least 600 g/L at 20.degree. C. In one aspect the acid has a
solubility in water of at least 700 g/L at 20.degree. C. In one
aspect the acid has a solubility in water of at least 800 g/L at
20.degree. C. In one aspect the acid has a solubility in water of
at least 900 g/L at 20.degree. C. In one aspect the acid has a
solubility in water of at least 1000 g/L at 20.degree. C. In one
aspect the acid has a solubility in water of at least 1100 g/L at
20.degree. C.
[0054] The amount of acid and the solubility of the acid may be
selected such that a given amount of the acid will dissolve in the
water. In one aspect at 20.degree. C. at least 20% of the acid
dissolves in the water. In one aspect at 25.degree. C. at least 20%
of the acid dissolves in the water. In one aspect at 30.degree. C.
at least 20% of the acid dissolves in the water. In one aspect at
20.degree. C. at least 35% of the acid dissolves in the water. In
one aspect at 20.degree. C. at least 40% of the acid dissolves in
the water. In one aspect at 20.degree. C. at least 45% of the acid
dissolves in the water. In one aspect at 20.degree. C. at least 50%
of the acid dissolves in the water. In one aspect at 20.degree. C.
at least 55% of the acid dissolves in the water.
[0055] In the aspects of the disclosure 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.
[0056] 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.
[0057] 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 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.
[0058] Nicotine
[0059] Nicotine formulations may be provided having desirable
properties of flavor, impact, irritation, smoothness and/or
nicotine reward for the user. In one aspect nicotine is present in
an amount of no greater than 6 wt % based on the total weight of
the aerosolizable formulation. In one aspect nicotine is present in
an amount of from 0.01 to 6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.02 to 6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.05 to 6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.08 to 6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.01 to 5 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.02 to 5 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.05 to 5 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.08 to 5 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of no greater than 4 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.01 to 4 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.02 to 4 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.05 to 4 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.08 to 4 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of no greater than 3 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.01 to 3 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.02 to 3 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.05 to 3 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.08 to 3 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of no greater than 2 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.01 to 2 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.02 to 2 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.05 to 2 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.08 to 2 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of no greater than 1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.01 to 1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.02 to 1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.05 to 1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.08 to 1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.1 to 1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of no greater than 0.6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.01 to 0.6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.02 to 0.6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.05 to 0.6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.08 to 0.6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.1 to 0.6 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of no greater than 0.5 wt % based on the total weight of the
aerosolizable 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
aerosolizable 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
aerosolizable 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
aerosolizable 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
aerosolizable formulation. In one aspect nicotine is present in an
amount of no greater than 0.2 wt % based on the total weight of the
aerosolizable 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
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.02 to 0.2 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.05 to 0.2 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.08 to 0.2 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of no greater than 0.1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.01 to 0.1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.02 to 0.1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.05 to 0.1 wt % based on the total weight of the
aerosolizable formulation. In one aspect nicotine is present in an
amount of from 0.08 to 0.1 wt % based on the total weight of the
aerosolizable formulation.
[0060] 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.
##STR00001##
[0061] 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.
[0062] 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 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.
[0063] In one aspect at least 5 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 10 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 15 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 20 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 25 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 30 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 35 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 40 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 45 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 50 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 55 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 60 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 65 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 70 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 75 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 80 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 85 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 90 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 95 wt % of the nicotine present in the
formulation is in protonated form. In one aspect at least 99 wt %
of the nicotine present in the formulation is in protonated form.
In one aspect at least 99.9 wt % of the nicotine present in the
formulation is in protonated form.
[0064] 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.
[0065] 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-yl) 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.
##STR00002##
[0066] The distribution of protonated and non-protonated nicotine
will vary at various pH increments.
##STR00003##
[0067] 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.
[0068] 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.sup.+BH.sup.+
[0069] The Henderson-Hasselbalch equation for this equilibrium
is:
pH = pKa + log .times. [ B ] [ BH + ] ##EQU00001##
[0070] Where [B] is the amount of non-protonated nicotine (i.e.
free base), [BH+] the amount of 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:
% .times. .times. protonated .times. .times. nicotine = 100 - { [ B
] [ BH + ] { 1 + [ B ] [ BH + ] } * 100 } ##EQU00002##
[0071] 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.
[0072] Flavor
[0073] As discussed herein, the aerosolizable formulation may
comprise one or more flavors or flavoring components. As used
herein, the terms "flavor" and "flavorantt" 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, pigment, ginger, anise, coriander, coffee, or a mint oil
from any species of the genus Mentha), flavor 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 flavors
may be selected from the group consisting of
(4-(para-)methoxyphenyl)-2-butanone, vanillin,
.gamma.-undecalactone, menthone, 5-propenyl guaethol, menthol,
para-mentha-8-thiol-3-one and mixtures thereof. In one aspect the
flavor is at least menthol.
[0074] If present, the one or more flavors may be present in any
suitable amount. In one aspect the one or more flavors are present
in a total amount of no greater than 10 wt. % based on the
aerosolizable formulation. In one aspect the one or more flavors
are present in a total amount of no greater than 7 wt. % based on
the aerosolizable formulation. In one aspect the one or more
flavors are present in a total amount of no greater than 5 wt. %
based on the aerosolizable formulation. In one aspect the one or
more flavors are present in a total amount of no greater than 4 wt.
% based on the aerosolizable formulation. In one aspect the one or
more flavors are present in a total amount of no greater than 3 wt.
% based on the aerosolizable formulation. In one aspect the one or
more flavors are present in a total amount of no greater than 2 wt.
% based on the aerosolizable formulation. In one aspect the one or
more flavors are present in a total amount of no greater than 1 wt.
% based on the aerosolizable formulation.
[0075] In one aspect the one or more flavors are present in a total
amount of from 0.01 to 5 wt. % based on the aerosolizable
formulation. In one aspect the one or more flavors are present in a
total amount of from 0.01 to 4 wt. % based on the aerosolizable
formulation. In one aspect the one or more flavors are present in a
total amount of from 0.01 to 3 wt. % based on the aerosolizable
formulation. In one aspect the one or more flavors are present in a
total amount of from 0.01 to 2 wt. % based on the aerosolizable
formulation. In one aspect the one or more flavors are present in a
total amount of from 0.01 to 1 wt. % based on the aerosolizable
formulation. In one aspect the one or more flavors are present in a
total amount of from 0.01 to 0.5 wt. % based on the aerosolizable
formulation.
[0076] Formulation
[0077] In one aspect, if the aerosolizable formulation contains one
or more cyclodextrins, then the aerosolizable formulation contains
no flavors that can be encapsulated by the one or more
cyclodextrins. In one aspect, if the aerosolizable formulation
contains one or more cyclodextrins, then the aerosolizable
formulation contains no flavors.
[0078] As will be appreciated, one or more cyclodextrins may or may
not be present in any suitable amount in the aerosolizable
formulation. In one aspect the one or more cyclodextrins are
present in a total amount of no greater than 12 wt. % based on the
aerosolizable formulation. In one aspect the one or more
cyclodextrins are present in a total amount of no greater than 10
wt. % based on the aerosolizable formulation. In one aspect the one
or more cyclodextrins are present in a total amount of no greater
than 9 wt. % based on the aerosolizable formulation. In one aspect
the one or more cyclodextrins are present in a total amount of no
greater than 8 wt. % based on the aerosolizable formulation. In one
aspect the one or more cyclodextrins are present in a total amount
of no greater than 7 wt. % based on the aerosolizable formulation.
In one aspect the one or more cyclodextrins are present in a total
amount of no greater than 6 wt. % based on the aerosolizable
formulation. In one aspect the one or more cyclodextrins are
present in a total amount of no greater than 5 wt. % based on the
aerosolizable formulation. In one aspect the one or more
cyclodextrins are present in a total amount of no greater than 4
wt. % based on the aerosolizable formulation. In one aspect the one
or more cyclodextrins are present in a total amount of no greater
than 3 wt. % based on the aerosolizable formulation. In one aspect
the one or more cyclodextrins are present in a total amount of no
greater than 2 wt. % based on the aerosolizable formulation. In one
aspect the one or more cyclodextrins are present in a total amount
of no greater than 1 wt. % based on the aerosolizable formulation.
In one aspect the one or more cyclodextrins are present in a total
amount of no greater than 0.1 wt. % based on the aerosolizable
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 aerosolizable 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 aerosolizable formulation.
[0079] The aerosolizable formulation of the present disclosure may
comprise one or more cyclodextrins. 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.
[0080] In one aspect the one or more cyclodextrins are selected
from the group consisting of unsubstituted (.alpha.)-cyclodextrin,
substituted (.alpha.)-cyclodextrin, unsubstituted
(.beta.)-cyclodextrin, substituted (.beta.)-cyclodextrin,
unsubstituted (.gamma.)-cyclodextrin, substituted
(.gamma.)-cyclodextrin, and mixtures thereof. In one aspect the one
or more cyclodextrins are selected from the group consisting of
unsubstituted (.beta.)-cyclodextrin, substituted
(.beta.)-cyclodextrin, and mixtures thereof.
[0081] In one aspect the one or more cyclodextrins are selected
from the group consisting of unsubstituted (.alpha.)-cyclodextrin,
unsubstituted (.beta.)-cyclodextrin, unsubstituted
(.gamma.)-cyclodextrin, and mixtures thereof. In one aspect the one
or more cyclodextrins is selected from unsubstituted
(.beta.)-cyclodextrin.
[0082] In one aspect the one or more cyclodextrins are selected
from the group consisting of substituted (.alpha.)-cyclodextrin,
substituted (.beta.)-cyclodextrin, substituted
(.gamma.)-cyclodextrin, and mixtures thereof. In one aspect the one
or more cyclodextrins is selected from substituted
(.beta.)-cyclodextrins. Chemical substitutions at the 2-, 3-, and
6-hydroxyl sites are envisaged, and in particular substitution at
the 2-position.
[0083] In one aspect the one or more cyclodextrins are selected
from the group consisting of 2-hydroxy-propyl-.alpha.-cyclodextrin,
2-hydroxy-propyl-.beta.-cyclodextrin,
2-hydroxy-propyl-.gamma.-cyclodextrin and mixtures thereof. In one
aspect the one or more cyclodextrins is at least
2-hydroxy-propyl-.alpha.-cyclodextrin. In one aspect the one or
more cyclodextrins is at least
2-hydroxy-propyl-.beta.-cyclodextrin. In one aspect the one or more
cyclodextrins is at least
2-hydroxy-propyl-.gamma.-cyclodextrin.
[0084] 2-hydroxy-propyl derivatives of cyclodextrins, such as
2-hydroxy-propyl-.beta.-cyclodextrin have increased solubility in
water when compared to base cyclodextrins such as
.beta.-cyclodextrin.
[0085] In further aspects, the aerosolizable formulation contains
cyclodextrins in a total amount of no greater than 0.001 wt. %
based on the aerosolizable formulation, such as cyclodextrins in a
total amount of no greater than 1.times.10.sup.-4 wt. % based on
the aerosolizable formulation, such as cyclodextrins in a total
amount of no greater than 1.times.10.sup.-5 wt. % based on the
aerosolizable formulation, such as cyclodextrins in a total amount
of no greater than 1.times.10.sup.-6 wt. % based on the
aerosolizable formulation. Thus in further aspects, the present
disclosure provides
[0086] (1) an aerosolizable formulation comprising
[0087] (i) water in an amount of at least 85 wt. % based on the
aerosolizable formulation; and
[0088] (ii) nicotine;
[0089] wherein cyclodextrins are present in a total amount of from
0 to 0.001 wt. % based on the aerosolizable formulation.
[0090] (2) a process for forming an aerosol, the process comprising
aerosolizing an aerosolizable formulation comprising
[0091] (i) water in an amount of at least 85 wt. % based on the
aerosolizable formulation; and
[0092] (ii) nicotine or one or more flavors;
[0093] wherein cyclodextrins are present in a total amount of from
0 to 0.001 wt. % based on the aerosolizable formulation.
[0094] (3) a contained aerosolizable formulation comprising
[0095] (a) a container; and
[0096] (b) an aerosolizable formulation, comprising [0097] (i)
water in an amount of at least 85 wt. % based on the aerosolizable
formulation; and [0098] (ii) nicotine; [0099] wherein cyclodextrins
are present in a total amount of from 0 to 0.001 wt. % based on the
aerosolizable formulation.
[0100] (4) an electronic aerosol provision system comprising:
[0101] (a) an aerosolizer for aerosolizing formulation for
inhalation by a user of the electronic aerosol provision
system;
[0102] (b) a power supply comprising a cell or battery for
supplying power to the aerosolizer
[0103] (c) an aerosolizable formulation, comprising [0104] (i)
water in an amount of at least 85 wt. % based on the aerosolizable
formulation; and [0105] (ii) nicotine or one or more flavors;
[0106] wherein cyclodextrins are present in a total amount of from
0 to 0.001 wt. % based on the aerosolizable formulation.
[0107] Process
[0108] As discussed herein, in one aspect there is provided a
process for forming an aerosol, the process comprising aerosolizing
an aerosolizable formulation comprising
[0109] (i) water in an amount of at least 85 wt. % based on the
aerosolizable formulation; and
[0110] (ii) nicotine or one or more flavors.
[0111] In a further aspect there is provided a process for forming
an aerosol, the process comprising aerosolizing an aerosolizable
formulation comprising
[0112] (i) water in an amount of at least 95 wt. % based on the
aerosolizable formulation; and
[0113] (ii) nicotine.
[0114] In the process the aerosol may be formed by a process
performed at a temperature below 60.degree. C. In the process the
aerosol may be formed by a process performed at a temperature below
50.degree. C. In the process the aerosol may be formed by a process
performed at a temperature below 40.degree. C. In the process the
aerosol may be formed by a process performed at a temperature below
30.degree. C. In the process the aerosol may be formed by a process
performed at a temperature below 25.degree. C. In the process the
aerosol may be formed by a process which does not involve
heating.
[0115] In the process the aerosol may be formed by applying
ultrasonic energy to the aerosolizable formulation.
[0116] In one aspect the aerosol the aerosol of the aerosolized
formulation has a D50 of from 2 to 6 .mu.m. 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). 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.
[0117] In one aspect the aerosol has a D50 of from 2.5 to 6 .mu.m.
In one aspect the aerosol has a D50 of from 3 to 6 .mu.m. In one
aspect the aerosol has a D50 of from 3.5 to 6 .mu.m. In one aspect
the aerosol has a D50 of from 4 to 6 .mu.m. In one aspect the
aerosol has a D50 of from 4.5 to 6 .mu.m. In one aspect the aerosol
has a D50 of from 5 to 6 .mu.m. In one aspect the aerosol has a D50
of from 2.5 to 5.5 .mu.m. In one aspect the aerosol has a D50 of
from 3 to 5.5 .mu.m. In one aspect the aerosol has a D50 of from
3.5 to 5.5 .mu.m. In one aspect the aerosol has a D50 of from 4 to
5.5 .mu.m. In one aspect the aerosol has a D50 of from 4.5 to 5.5
.mu.m. In one aspect the aerosol has a D50 of from 5 to 5.5
.mu.m.
[0118] In one aspect the aerosol has a D10 of at least 0.5 .mu.m.
In one aspect the aerosol has a D10 of at least 1 .mu.m. In one
aspect the aerosol has a D10 of at least 2 .mu.m.
[0119] In one aspect the aerosol has a D90 of no greater than 15
.mu.m. In one aspect the aerosol has a D90 of no greater than 12
.mu.m. In one aspect the aerosol has a D90 of no greater than 10
.mu.m.
[0120] In one aspect D50 is measured after exclusion of particles
having a particle size of less than 1 .mu.m. In one aspect D10 is
measured after exclusion of particles having a particle size of
less than 1 .mu.m. In one aspect D90 is measured after exclusion of
particles having a particle size of less than 1 .mu.m.
[0121] The formulation may be contained or delivered by any means.
In one aspect the present disclosure provides a contained
aerosolizable formulation comprising (a) one or more containers;
and (b) an aerosolizable 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.
[0122] As discussed herein, the container of the present disclosure
is typically provided for the delivery of aerosolizable formulation
to or within an e-cigarette. The aerosolizable 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 cartomizer which typically comprises a reservoir of
aerosolizable formulation, an aerosolizer such as a wick material
and a heating element for vaporizing the aerosolizable formulation.
In some e-cigarettes, the cartomizer is part of a single-piece
device and is not detachable. In one aspect the container is a
cartomizer or is part of a cartomizer. In one aspect the container
is not a cartomizer or part of a cartomizer and is a container,
such as a tank, which may be used to deliver nicotine formulation
to or within an e-cigarette.
[0123] In one aspect the container is part of an e-cigarette.
Therefore in a further aspect the present disclosure provides an
electronic aerosol provision system comprising: an aerosolizable
formulation as defined herein; an aerosolizer for aerosolizing
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 aerosolizer.
[0124] The process of the present disclosure may comprises
additional steps either before the steps listed, after the steps
listed or between one or more of the steps listed.
[0125] The disclosure will now be described with reference to the
following non-limiting examples.
EXAMPLES
Example 1
[0126] A series of tests were conducted using commercially
available vibrating mesh nebulizer devices. The "control" device
was loaded with formulation containing 90.0% (w/w) water, 8.8%
(w/w) propylene glycol containing flavor, and 1.2% (w/w)
nicotine.
[0127] A similar device was prepared wherein 10.0% w/w glycerol was
added to the formulation, with the water content was commensurately
reduced to 80.0% (w/w).
[0128] A similar device was prepared wherein 10.0% w/w propylene
glycol was added to the formulation, with the water content was
commensurately adjusted to 80.0% (w/w).
[0129] A similar device was prepared wherein 5.0% w/w glycerol and
5.0% (w/w) propylene glycol was added to the formulation, with the
water content was commensurately adjusted to 80.0% (w/w).
[0130] A similar device was prepared wherein 20.0% w/w glycerol was
added to the formulation, with the water content was commensurately
reduced to 70.0% (w/w).
[0131] A similar device was prepared wherein 20.0% w/w propylene
glycol was added to the formulation, with the water content was
commensurately adjusted to 70.0% (w/w).
[0132] A similar device was prepared wherein 10.0% w/w glycerol and
10.0% propylene glycol was added to the formulation, with the water
content was commensurately adjusted to 70.0% (w/w).
[0133] One each of these devices was presented to eight (8)
panelists comprising e-cigarette users, and the panelists were
asked to puff on the devices in a sequential monadic fashion for
five (5) puffs on each device. Each panelists was asked to choose a
palatable flavor of their choosing to aid feedback regarding water,
glycerol and propylene glycol composition.
[0134] Eight (8) panelists preferred the formulations that did not
contain propylene glycol or glycerol in a concentration higher than
10.0% (w/w). Five (5) people preferred the formulation in the
control device and 3 people preferred the formulation with 10%
glycerol.
Example 2
[0135] Three Amaretto flavored and three non-flavored formulations
were blindly assessed by up to 9 panelists, who are experienced
vapors with different nicotine tolerances. During the sensory
evaluation the panelists ranked several sensory attributes such as
throat irritation and chest impact from low (1) to high (9). The
panelists were also asked to indicate the most favorite formulation
among the tested. A series of tests were conducted using
commercially available vibrating mesh nebulizer devices.
[0136] The devices were loaded with formulations containing
[0137] Formulation 1--82% (w/w) water, 9.4% (w/w)
2-hydroxy-propyl-.beta.-cyclodextrin, 8% (w/w) glycerol, and 0.6%
(w/w) nicotine.
[0138] Formulation 2--85% (w/w) water, 9.4% (w/w)
2-hydroxy-propyl-.beta.-cyclodextrin, 5% (w/w) glycerol, and 0.6%
(w/w) nicotine.
[0139] Formulation 3--87% (w/w) water, 9.4% (w/w)
2-hydroxy-propyl-.beta.-cyclodextrin, 3% (w/w) glycerol, and 0.6%
(w/w) nicotine.
[0140] Formulation 4--82% (w/w) water, 2.0% (w/w) propylene glycol
containing amaretto flavor, 9.8% (w/w) glycerol, 5% (w/w) ethanol,
0.6% (w/w) nicotine and 0.6% (w/w) citric acid.
[0141] Formulation 5--85% (w/w) water, 2.0% (w/w) propylene glycol
containing amaretto flavor, 6.8% (w/w) glycerol, 5% (w/w) ethanol,
0.6% (w/w) nicotine and 0.6% (w/w) citric acid.
[0142] Formulation 6--87% (w/w) water, 2.0% (w/w) propylene glycol
containing amaretto flavor, 4.8% (w/w) glycerol, 5% (w/w) ethanol,
0.6% (w/w) nicotine and 0.6% (w/w) citric acid.
[0143] The summary of tested formulations is presented in the table
below.
TABLE-US-00001 Formulation Water, No Formulation No. Name w/w %
panelist Liked 1 Base 82 82 7 1 2 Base 85 85 7 5 3 Base 87 87 7 1 4
Amaretto 82 82 9 1 5 Amaretto 85 85 9 4 6 Amaretto 87 87 9 4
[0144] Five (5) out of seven (7) panelists preferred non flavored
formulation with 85% (w/w) water content, one (1) out of seven (7)
panelists preferred non flavored formulation with 87% (w/w) water
content, while only one (1) panelist preferred non flavored
formulation with 82% (w/w) water content.
[0145] Eight (8) out of nine (9) panelists preferred Amaretto
flavored formulation with 85% and 87% (w/w) water content, while
only one (1) panelist preferred Amaretto flavored formulation with
82% (w/w) water content.
[0146] 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.
* * * * *