WO2022094358A1

WO2022094358A1 - Aqueous formulation for aerosolizing and inhaling using electronic devices

Info

Publication number: WO2022094358A1
Application number: PCT/US2021/057477
Authority: WO
Inventors: Mario Danek; Christopher Kar-Heng Cheng; Joseph Gene Walsh; Brian Quigley
Original assignee: Respira Technologies, Inc.
Priority date: 2020-11-01
Filing date: 2021-10-30
Publication date: 2022-05-05
Also published as: TW202233078A

Abstract

An aqueous formulation for aerosolizing and inhaling using electronic device includes a saline component, an acid component, and a nicotine component. The acid component includes a lactic acid. The aqueous formulation optionally includes one or more of a menthol component, an ethanol component, and a surfactant component.

Description

AQUEOUS FORMUUATION FOR AEROSOUIZING AND INHALING USING ELECTRONIC DEVICES

COPYRIGHT STATEMENT

[ 001 ] Any new and original work of authorship in this document is subject to copyright protection under the copyright laws of the United States and other countries. Reproduction by anyone of this document as it appears in official governmental records is permitted, but otherwise all other copyright rights whatsoever are reserved.

BACKGROUND OF THE INVENTION

[ 002 ] The invention generally relates to formulations and methods pertaining to liquids that are aerosolized and inhaled by persons using electronic devices, whether intended for personal or recreational use, or for the administration of medicines.

[ 003 ] Inhalation delivery systems now play an increasing role in the targeted delivery of active ingredients to the human pulmonary system. This is true both for medical purposes, such as the targeted delivery of anti-cancer medications to the lungs, as well as for recreational/personal purposes, such as vaping, in which a liquid that includes the active ingredient is vaporized using heating so that the active ingredient can be inhaled into the human body.

[ 004 ] Unfortunately, as inhalation delivery systems using heating have increased in prominence, concerns about their short and long term safety have come into focus. This is particularly true for vaping where there exist ongoing concerns about the possible presence of harmful and potentially harmful constituents (HPHCs) in the inhaled vapor.

[ 005 ] In the context of vaping, nicotine is among the most common components that is included in liquid formulations that are aerosolized and inhaled. Many nicotine -containing liquid formulations available today use solvents such as propylene glycol or glycerol. However, in view of ongoing research and health concerns, there is growing interest in developing nicotine -containing formulations in aqueous solutions. In developing aqueous formulations, challenges can arise with respect to ascertaining an effective combination of components to arrive at a formulation that is both safe and provides a user with an appealing sensorial experience. For example, at higher nicotine concentrations, the formulation is known to create a “harsh” sensorial experience for a user.

[ 006 ] Accordingly, a need exists for an aqueous formulation for aerosolizing and inhaling using electronic devices that balances the concerns of safety and pleasant user experience. This, and other needs, are believed to be addressed by one or more aspects and features of the invention.

SUMMARY OF THE INVENTION

[ 007 ] The invention includes many aspects and features. Moreover, while many aspects and features relate to, and are described in, the context of nicotine-based aqueous formulations, the invention is not limited to use only in nicotine-based aqueous formulations, as will become apparent from the following summaries and detailed descriptions of aspects, features, and one or more embodiments of the invention.

[ 008 ] In accordance with one aspect, an aqueous formulation for aerosolizing and inhaling using electronic devices includes a saline component, an acid component, and a nicotine component. The acid component includes a lactic acid.

[ 009 ] In a feature, the saline component includes a 0.9% NaCl saline solution.

[ 010 ] In a feature, the saline component is approximately 30% by mass to approximately 99.998% by mass of the formulation.

[ oil ] In a feature, the acid component further includes one or more of benzoic acid, malic acid, tartaric acid, salicylic acid, levulinic acid, and hydrochloric acid.

[ 012 ] In a feature, the acid component is approximately 0.001% by mass to approximately 25% by mass of the formulation.

[ 013 ] In a feature, the nicotine component includes nicotine in a protonated form and nicotine in an unprotonated form.

[ 014 ] In a feature, the nicotine component is approximately 0.001 % by mass to approximately 5 % by mass of the formulation.

[ 015 ] In a feature, a pH value of the aqueous formulation measures between approximately 2 and approximately 5.

[ 016 ] In a feature, the pH value of the aqueous formulation measures approximately 3.38.

[ 017 ] In a feature, the aqueous formulation further includes a menthol component.

[ 018 ] In a feature, the menthol component is approximately 0.001% by mass to approximately 15% by mass of the formulation.

[ 019 ] In a feature, the aqueous formulation further includes an ethanol component.

[ 020 ] In a feature, the ethanol component is approximately 0.001% by mass to approximately 10% by mass of the formulation.

[ 021 ] In a feature, the aqueous formulation further includes a surfactant component, wherein the surfactant component includes one or more different surfactants.

[ 022 ] In a feature, the surfactant component includes one or more of polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monolaurate, lecithin, and a poloxamer.

[ 023 ] In a feature, the surfactant component is approximately 0.001 % by mass to approximately 10% by mass of the formulation.

[ 024 ] In a feature, the aqueous formulation further includes an ethanol component and a surfactant component. [ 025 ] In accordance with another aspect, a method of preparing an aqueous formulation for aerosolizing and inhaling using electronic devices includes mixing a nicotine component and an acid component to form a first mixture, separately mixing a menthol component and a saline component to form a second mixture, and mixing the first mixture and the second mixture to form a target aqueous formulation.

[ 026 ] In accordance with another aspect, a method of preparing an aqueous formulation for aerosolizing and inhaling using electronic devices includes mixing a nicotine component and an acid component to form a first mixture, separately mixing a menthol component and an ethanol component to form a second mixture, mixing a saline component with the second mixture to form a third mixture, and mixing the first mixture and the third mixture to form a target aqueous formulation.

[ 027 ] In accordance with another aspect, a method of preparing an aqueous formulation for aerosolizing and inhaling using electronic devices includes mixing a nicotine component and an acid component to form a first mixture, mixing a saline component with the first mixture to form a second mixture, separately mixing a menthol component, an ethanol component, and a surfactant component to form a third mixture, and mixing the second mixture and the third mixture to form a target aqueous formulation.

[ 028 ] In a feature, the acid component includes a lactic acid, and the surfactant component includes polyoxyethylene sorbitan monooleate.

[ 029 ] In addition to the aforementioned aspects and features of the invention, it should be noted that the invention further encompasses the various logical combinations and subcombinations of such aspects and features. Thus, for example, claims in this or a divisional or continuing patent application or applications may be separately directed to any aspect, feature, or embodiment disclosed herein, or combination thereof, without requiring any other aspect, feature, or embodiment.

BRIEF DESCRIPTION OF THE DRAWINGS

[ 030 ] One or more preferred embodiments of the invention now will be described in detail with reference to the accompanying drawings, wherein the same elements are referred to with the same reference numerals, and wherein,

[ 031 ] FIGS . 1 A- 1 C are structural formulae for unprotonated nicotine, monoprotonated nicotine, and diprotonated nicotine, respectively;

[ 032 ] FIG. 1 D is a graphical representation illustrating the relationship between pH and the relative fraction of each species of FIGS. 1A-1C in solution;

[ 033 ] FIG. 2 is a graphical representation illustrating the relationship between total nicotine concentration and an unprotonated fraction of total nicotine and how that relationship can inform a sensory experience; [ 034 ] FIG. 3 is a graphical representation illustrating a harshness measurement of a menthol- containing formulation as a function of total nicotine concentration;

[ 035 ] FIG. 4 is a flowchart illustrating a method of preparing an aqueous formulation, in accordance with one or more aspects of the invention, which includes a saline component, a nicotine component, and an acid component;

[ 036 ] FIG. 5 is a flowchart illustrating a method of preparing an aqueous formulation, in accordance with one or more aspects of the invention, which includes a saline component, a nicotine component, an acid component, and a menthol component;

[ 037 ] FIG. 6 is a flowchart illustrating a method of preparing an aqueous formulation, in accordance with one or more aspects of the invention, which includes a saline component, a nicotine component, an acid component, a menthol component, and an ethanol component; and [ 038 ] FIG. 7 is a flowchart illustrating a method of preparing an aqueous formulation, in accordance with one or more aspects of the invention, which includes a saline component, a nicotine component, an acid component, a menthol component, an ethanol component, and a surfactant component.

DETAILED DESCRIPTION

[039] As a preliminary matter, it will readily be understood by one having ordinary skill in the relevant art (“Ordinary Artisan”) that the invention has broad utility and application. Furthermore, any embodiment discussed and identified as being “preferred” is considered to be part of a best mode contemplated for carrying out the invention. Other embodiments also may be discussed for additional illustrative purposes in providing a full and enabling disclosure of the invention. Furthermore, an embodiment of the invention may incorporate only one or a plurality of the aspects of the invention disclosed herein; only one or a plurality of the features disclosed herein; or combination thereof. As such, many embodiments are implicitly disclosed herein and fall within the scope of what is regarded as the invention.

[040] Accordingly, while the invention is described herein in detail in relation to one or more embodiments, it is to be understood that this disclosure is illustrative and exemplary of the invention and is made merely for the purposes of providing a full and enabling disclosure of the invention. The detailed disclosure herein of one or more embodiments is not intended, nor is to be construed, to limit the scope of patent protection afforded the invention in any claim of a patent issuing here from, which scope is to be defined by the claims and the equivalents thereof. It is not intended that the scope of patent protection afforded the invention be defined by reading into any claim a limitation found herein that does not explicitly appear in the claim itself.

[041] Thus, for example, any sequence(s) and/or temporal order of steps of various processes or methods that are described herein are illustrative and not restrictive. Accordingly, it should be understood that, although steps of various processes or methods may be shown and described as being in a sequence or temporal order, the steps of any such processes or methods are not limited to being carried out in any particular sequence or order, absent an indication otherwise. Indeed, the steps in such processes or methods generally may be carried out in various different sequences and orders while still falling within the scope of the invention. Accordingly, it is intended that the scope of patent protection afforded the invention be defined by the issued claim(s) rather than the description set forth herein.

[042] Additionally, it is important to note that each term used herein refers to that which the Ordinary Artisan would understand such term to mean based on the contextual use of such term herein. To the extent that the meaning of a term used herein — as understood by the Ordinary Artisan based on the contextual use of such term — differs in any way from any particular dictionary definition of such term, it is intended that the meaning of the term as understood by the Ordinary Artisan should prevail.

[043] With regard solely to construction of any claim with respect to the United States, no claim element is to be interpreted under 35 U.S.C. 112(f) unless the explicit phrase “means for” or “step for” is actually used in such claim element, whereupon this statutory provision is intended to and should apply in the interpretation of such claim element. With regard to any method claim including a condition precedent step, such method requires the condition precedent to be met and the step to be performed at least once but not necessarily every time during performance of the claimed method.

[044] Furthermore, it is important to note that, as used herein, “comprising” is open-ended insofar as that which follows such term is not exclusive. Additionally, “a” and “an” each generally denotes “at least one” but does not exclude a plurality unless the contextual use dictates otherwise. Thus, reference to “a picnic basket having an apple” is the same as “a picnic basket comprising an apple” and “a picnic basket including an apple”, each of which identically describes “a picnic basket having at least one apple” as well as “a picnic basket having apples”; the picnic basket further may contain one or more other items beside an apple. In contrast, reference to “a picnic basket having a single apple” describes “a picnic basket having only one apple”; the picnic basket further may contain one or more other items beside an apple. In contrast, “a picnic basket consisting of an apple” has only a single item contained therein, i.e., one apple; the picnic basket contains no other item.

[045] When used herein to join a list of items, “or” denotes “at least one of the items” but does not exclude a plurality of items of the list. Thus, reference to “a picnic basket having cheese or crackers” describes “a picnic basket having cheese without crackers”, “a picnic basket having crackers without cheese”, and “a picnic basket having both cheese and crackers”; the picnic basket further may contain one or more other items beside cheese and crackers.

[046] When used herein to join a list of items, “and” denotes “all of the items of the list”. Thus, reference to “a picnic basket having cheese and crackers” describes “a picnic basket having cheese, wherein the picnic basket further has crackers”, as well as describes “a picnic basket having crackers, wherein the picnic basket further has cheese”; the picnic basket further may contain one or more other items beside cheese and crackers.

[ 047 ] The phrase “at least one” followed by a list of items joined by “and” denotes an item of the list but does not require every item of the list. Thus, “at least one of an apple and an orange” encompasses the following mutually exclusive scenarios: there is an apple but no orange; there is an orange but no apple; and there is both an apple and an orange. In these scenarios if there is an apple, there may be more than one apple, and if there is an orange, there may be more than one orange. Moreover, the phrase “one or more” followed by a list of items joined by “and” is the equivalent of “at least one” followed by the list of items joined by “and”.

[ 048 ] Referring now to the drawings, one or more preferred embodiments in accordance with one or more aspects and features of the invention are next described. The following description of one or more preferred embodiments is merely exemplary in nature and is in no way intended to limit the invention, its implementations, or uses.

[ 049 ] FIGS. 1A-1C are structural formulae for unprotonated nicotine, monoprotonated nicotine, and diprotonated nicotine, respectively. In its unprotonated (or “free-base”) form, which is depicted in FIG. 1A, nicotine is a weak base having a pK_a value of 8.0. As shown in FIG. 1A, the unprotonated form of nicotine includes two nitrogen atoms that exhibit basic properties. By adding one proton to one of the two nitrogen atoms, the unprotonated form becomes a monoprotonated form, which is depicted in FIG. IB. Adding another proton to the other of the two nitrogen atoms transitions the monoprotonated form to a diprotonated form, which is depicted in FIG. 1C. In the mono- and diprotonated forms, nicotine is less volatile than the unprotonated form.

[ 050 ] FIG. ID is a graphical representation illustrating the relationship between pH and the relative fraction of each species of FIGS. 1A-1C in solution. As shown in FIG. ID, the relative dominance of the unprotonated form in a solution tends to shift in favor of the protonated forms around a pH of 8. At moderately acidic to slightly basic pH values in the approximately 3.5 to approximately 8 range, the monoprotonated form is the dominant species in solution. And, at pH values of approximately 3.5 and lower, the diprotonated form is the dominant species in solution. In this regard, it is contemplated that an acid can be added to unprotonated nicotine to adjust the pH and increase the ratio of protonated nicotine species, which includes both monoprotonated and diprotonated species, in solution.

[ 051 ] FIG. 2 is a graphical representation illustrating the relationship between total nicotine concentration and an unprotonated fraction of total nicotine and how that relationship can inform a sensory experience. As a basic compound, nicotine in its unprotonated form is understood to yield a harsh sensory experience at higher nicotine concentrations. As illustrated in FIG. 2, the harshness of the sensory experience can be mitigated when the fraction of unprotonated nicotine is reduced relative to the overall amount of nicotine present in solution. [052 ] FIG. 3 is a graphical representation illustrating a harshness measurement of a menthol- containing formulation as a function of total nicotine concentration. It is contemplated that a harsh sensory experience arising from nicotine inhalation can be further mitigated by the inclusion of menthol in solution. As depicted in FIG. 3, a menthol concentration of approximately 3.5% can reduce the irritation/harshness sensory effect at higher nicotine concentrations (such as at nicotine concentrations of 18 mg/mL or greater). This mitigation of the harshness effect can be coupled with other favorable characteristics of menthol, including a strong cooling sensation and strong overall intensity.

[053 ] With reference to FIGS . 2 and 3 , it is contemplated that an overall sensorial appeal of aerosolizable and inhalable aqueous formulations can be informed by considerations of one or more of total nicotine amount, a ratio of unprotonated nicotine relative to the total nicotine amount, and menthol. [054 ] In some contemplated embodiments, an aqueous formulation for aerosolizing and inhaling using electronic devices includes a total nicotine concentration of approximately 20 mg/mL in an aqueous solution. To achieve a desired ratio of unprotonated nicotine to protonated nicotine (including monoprotonated and diprotonated forms) in such a formulation, an acid can be added until an unprotonated fraction of approximately 0.2 to approximately 0.35 is achieved relative to the total nicotine amount. With further reference to FIG. 2, a zone of interest for such a formulation is reflected by the portion of the graphical representation marked by A, with preference given to the portion marked by B. When considered in light of the graphical representation of FIG. ID, a target pH for achieving an unprotonated fraction of approximately 0.2 to approximately 0.35 falls between the 6 to 8 range. For example, a species that includes approximately 0.3 unprotonated fraction may require a target pH of approximately 7.5, which is depicted in FIG. ID with a line marked by C. Additionally, it is contemplated that menthol can be included in the formulation to enhance the sensory experience and reduce harshness.

[055] In other contemplated embodiments, an aqueous formulation for aerosolizing and inhaling using electronic devices includes a saline component, a nicotine component, an acid component, and, optionally, one or both of a menthol component and an ethanol component. Contemplated mass percent ranges for each component for such a formulation include: a saline component having approximately 30% by mass to approximately 99.998% by mass of the solution; a nicotine component having approximately 0.001% by mass to approximately 5% by mass of the solution; an acid component having approximately 0.001% by mass to approximately 25% by mass of the solution; a menthol component having 0% by mass to approximately 15% by mass of the solution; and an ethanol component having 0% by mass to approximately 25% by mass of the solution.

[056] It is contemplated that the saline component is a safe, aqueous solution that resembles or approximates a physiologically normal solution. One preferred form of saline for use as a saline component in the aqueous formulation is an isotonic saline, such as 0.9% NaCl saline solution. It is further contemplated that hypotonic or hypertonic saline can be used. In this regard, a saline solution may fall within a range of approximately 0.001% to approximately 7.5% NaCl saline solution. In still other contemplated embodiments, water is used in place of a saline component.

[057] The acid component functions to reduce the fraction of unprotonated nicotine relative to the overall nicotine amount. One preferred acid for use as an acid component in the aqueous formulation is lactic acid. Other contemplated acids include, but are not limited to, benzoic acid, malic acid, tartaric acid, salicylic acid, levulinic acid, and hydrochloric acid.

[058] As discussed above, menthol can optionally be included in the aqueous formulation to enhance the sensory experience and reduce harshness. Other flavorants and components are likewise contemplated in addition to (or in place of) menthol.

[059] It is contemplated that ethanol can optionally be included in the aqueous formulation as a surfactant or as a cosolvent. Other contemplated cosolvents include, but are not limited to, propylene glycol and glycerin.

[060] One specific contemplated formulation in accordance with the above-described features includes: a 0.9% NaCl saline component having approximately 93.486% by mass of the solution; a nicotine component having approximately 2% by mass of the solution; a lactic acid component having approximately 4.477% by mass of the solution; and a menthol component having approximately 0.037% by mass of the solution.

[061] FIG. 4 is a flowchart illustrating a method 100 of preparing an aqueous formulation, in accordance with one or more aspects of the invention, which includes a saline component, a nicotine component, and an acid component. In a first step 105, the nicotine component and the acid component are combined to form a nicotine salt mixture. In embodiments where the acid component includes a lactic acid, the nicotine component and the acid component combine to form a nicotine lactate mixture. In a second step 110, the nicotine salt mixture is combined with the saline solution to create the target formulation for aerosolizing and inhaling using electronic devices.

[062 ] FIG. 5 is a flowchart illustrating a method 200 of preparing an aqueous formulation, in accordance with one or more aspects of the invention, which includes a saline component, a nicotine component, an acid component, and a menthol component. In a first step 205, the nicotine component and the acid component are combined to form a nicotine salt mixture. In embodiments where the acid component includes a lactic acid, the nicotine component and the acid component combine to form a nicotine lactate mixture. In a second step 210, the menthol component is separately combined with the saline component to form a menthol/saline mixture. Then, in a third step 215, the nicotine salt mixture from the first step 205 is combined with the menthol/saline mixture from the second step 210 to create the target formulation for aerosolizing and inhaling using electronic devices. [063 ] FIG. 6 is a flowchart illustrating a method 300 of preparing an aqueous formulation, in accordance with one or more aspects of the invention, which includes a saline component, a nicotine component, an acid component, a menthol component, and an ethanol component. In a first step 305, the nicotine component and the acid component are combined to form a nicotine salt mixture. In embodiments where the acid component includes a lactic acid, the nicotine component and the acid component combine to form a nicotine lactate mixture. In a second step 310, the menthol component is separately combined with the ethanol component to form a menthol/ethanol mixture. As discussed above, it is contemplated that the ethanol component can be included as a surfactant or as a cosolvent. In this regard, it is noted that components added to the solution that are beyond the solubility limit of menthol may require a surfactant. In this regard, it is contemplated that use of a surfactant allows components above a solubility limit to be included in a mixture through formation of an emulsion. Surfactant molecules interrelate to form a structure capable of encapsulating an otherwise insoluble component. In a third step 315, the menthol/ethanol mixture from the second step 310 is combined with the saline component to create a menthol/ethanol/saline mixture. Then, in a fourth step 320, the nicotine salt mixture from the first step 305 is combined with the menthol/ethanol/saline mixture from the third step 315 to create the target formulation for aerosolizing and inhaling using electronic devices.

[064 ] In still other contemplated embodiments, an aqueous formulation for aerosolizing and inhaling using electronic devices includes a saline component, a nicotine component, an acid component, and, optionally, any one or any combination of a menthol component, an ethanol component, and a surfactant component. Contemplated mass percent ranges for each component for such a formulation include: a saline component having approximately 35% by mass to approximately 99.998% by mass of the solution; a nicotine component having approximately 0.001% by mass to approximately 5% by mass of the solution; an acid component having approximately 0.001% by mass to approximately 25% by mass of the solution; a menthol component having 0% by mass to approximately 15% by mass of the solution; an ethanol component having 0% by mass to approximately 10% by mass of the solution; and a surfactant component having 0% by mass to approximately 10% by mass of the solution.

[065] It is contemplated that the saline component is a safe, aqueous solution that resembles or approximates a physiologically normal solution. One preferred form of saline for use as a saline component in the aqueous formulation is an isotonic saline, such as 0.9% NaCl saline solution. It is further contemplated that hypotonic or hypertonic saline can be used. In this regard, a saline solution may fall within a range of approximately 0.001% to approximately 7.5% NaCl saline solution. In still other contemplated embodiments, water is used in place of a saline component.

[066] The acid component functions to reduce the fraction of unprotonated nicotine relative to the overall nicotine amount. One preferred acid for use as an acid component in the aqueous formulation is lactic acid. Other contemplated acids include, but are not limited to, benzoic acid, malic acid, tartaric acid, salicylic acid, levulinic acid, and hydrochloric acid.

[067] As discussed above, menthol can optionally be included in the aqueous formulation to enhance the sensory experience and reduce harshness. Other flavorants and components are likewise contemplated in addition to (or in place of) menthol.

[068] It is contemplated that ethanol can optionally be included in the aqueous formulation as a surfactant or as a cosolvent. Other contemplated cosolvents include, but are not limited to, propylene glycol and glycerin.

[069] The surfactant component can help to reduce the surface tension of the liquid solution in which it is dissolved. Surfactant molecules in solution can group together to form a micelle or liposomal structure to encapsulate target ingredients or components in solution. In this regard, an emulsion or nanoemulsion can be formed so that otherwise insoluble components can be encapsulated by surfactants and remain part of the mixture. In at least some embodiments, it is contemplated that a microfluidics approach (using a microfluidics machine) can be utilized to form a nanoemulsion through the interaction of liquid streams in defined microchannels. For additional discussion of surfactants as encapsulating agents for pulmonary delivery of specific ingredients or components to the alveolar lung by inhalation, reference is made to co-pending and commonly assigned U.S. Patent Application Serial No. 17/075,679, which is incorporated by reference herein.

[070] It is contemplated that surfactants for use in an aqueous formulation in accordance with one or more aspects of the present invention may include, but are not limited to: high purity polyoxyethylene sorbitan monooleate (also known by its trade name, SUPER REFINED® Polysorbate 80); polyoxyethylene sorbitan monooleate; (also known by its trade name, TWEEN® Polysorbate 80); polyoxyethylene sorbitan monostearate (also known by its trade name TWEEN® Polysorbate 60); polyoxyethylene sorbitan monopalmitate (also known by its trade name TWEEN® Polysorbate 40); polyoxyethylene sorbitan monolaurate (also known by its trade name TWEEN® Polysorbate 20); lecithin; dipalmitoylphosphatidylcholine (DPPC); l,2-distearoyl-5«-glycero-3 -phosphocholine (DSPC); sorbitan monostearate (also known by its trade name SPAN 60); sorbitan monopalmitate (also known by its trade name SPAN 40); and a poloxamer (such as poloxamer 188 or poloxamer 447). It is further contemplated that an aqueous formulation in accordance with one or more aspects of the present invention can include a single surfactant or can include multiple surfactants.

[071] One specific contemplated formulation in accordance with the above-described features includes: a 0.9% NaCl saline component having approximately 91.291% by mass of the solution; a nicotine component having approximately 2.001% by mass of the solution; a lactic acid component having approximately 4.479% by mass of the solution; a menthol component having approximately 2.229% by mass of the solution; an ethanol component having approximately 1.758% by mass of the solution; and a TWEEN® Polysorbate 80 surfactant component having approximately 2.377% by mass of the solution.

[072 ] FIG. 7 is a flowchart illustrating a method 400 of preparing an aqueous formulation, in accordance with one or more aspects of the invention, which includes a saline component, a nicotine component, an acid component, a menthol component, an ethanol component, and a surfactant component. In a first step 405, the nicotine component and the acid component are combined to form a nicotine salt mixture. In embodiments where the acid component includes a lactic acid, the nicotine component and the acid component combine to form a nicotine lactate mixture. Then, in a second step 410, the nicotine salt mixture from the first step 405 is combined with the saline component to create a nicotine salt/saline mixture. In a third step 415, the menthol component, the ethanol component, and the surfactant component are separately combined to form a menthol/ethanol/surfactant mixture. In contemplated embodiments, the surfactant component includes TWEEN® Polysorbate 80. Additionally, as discussed above, it is contemplated that the ethanol component can be included as a surfactant or as a cosolvent. In this regard, it is noted that components added to the solution that are beyond the solubility limit of menthol may require a surfactant. Then, in a fourth step 420, the nicotine salt/saline mixture from the second step 410 is combined with the menthol/ethanol/surfactant mixture from the third step 415 to create the target formulation for aerosolizing and inhaling using electronic devices. When a surfactant, such as TWEEN® Polysorbate 80, is used in the aqueous formulation, the sequence of preparation steps can help to prevent a constituent from precipitating as a solid during mixing of components. In particular, where menthol and a surfactant are both used in the aqueous formulation, combining the nicotine component and the acid component separately from the menthol component and the surfactant component helps to prevent menthol from precipitating out of the system when the separately combined components are mixed together to create the target formulation.

[073 ] As discussed above, pH level measurements can be used to help inform regarding the fraction of different nicotine species in solution. pH level can also function as a gauge for overall sensory experience upon aerosolizing and inhaling an aqueous formulation. In contemplated embodiments, a target pH range for providing a pleasant sensory experience to users places the pH measurement of an aqueous formulation from approximately 2 to approximately 7. In at least some embodiments, a target pH value within a range of approximately 2 to approximately 5 is preferred. Furthermore, in at least some embodiments, a target pH value of approximately 3.38 reflects a particularly favorable sensory experience that mitigates harshness that may arise at higher nicotine concentrations.

[074 ] Based on the foregoing description, it will be readily understood by those persons skilled in the art that the invention has broad utility and application. Many embodiments and adaptations of the invention other than those specifically described herein, as well as many variations, modifications, and equivalent arrangements, will be apparent from or reasonably suggested by the invention and the foregoing descriptions thereof, without departing from the substance or scope of the invention.

Accordingly, while the invention has been described herein in detail in relation to one or more preferred embodiments, it is to be understood that this disclosure is only illustrative and exemplary of the invention and is made merely for the purpose of providing a full and enabling disclosure of the invention. The foregoing disclosure is not intended to be construed to limit the invention or otherwise exclude any such other embodiments, adaptations, variations, modifications or equivalent arrangements, the invention being limited only by the claims appended hereto and the equivalents thereof.

Claims

What is claimed is:

1. An aqueous formulation for aerosolizing and inhaling using electronic devices, the formulation comprising: a saline component; an acid component, wherein the acid component includes a lactic acid; and a nicotine component.

2. The aqueous formulation of claim 1, wherein the saline component includes a 0.9% NaCl saline solution.

3. The aqueous formulation of claim 1, wherein the saline component is approximately 30% by mass to approximately 99.998% by mass of the formulation.

4. The aqueous formulation of claim 1, wherein the acid component further includes one or more of benzoic acid, malic acid, tartaric acid, salicylic acid, levulinic acid, and hydrochloric acid.

5. The aqueous formulation of claim 1, wherein the acid component is approximately 0.001% by mass to approximately 25% by mass of the formulation.

6. The aqueous formulation of claim 1, wherein the nicotine component includes nicotine in a protonated form and nicotine in an unprotonated form.

7. The aqueous formulation of claim 1, wherein the nicotine component is approximately 0.001% by mass to approximately 5% by mass of the formulation.

8. The aqueous formulation of claim 1, wherein a pH value of the aqueous formulation measures between approximately 2 and approximately 5.

9. The aqueous formulation of claim 1, wherein the pH value of the aqueous formulation measures approximately 3.38.

10. The aqueous formulation of claim 1, further comprising a menthol component.

11. The aqueous formulation of claim 10, wherein the menthol component is approximately 0.001% by mass to approximately 15% by mass of the formulation.

12. The aqueous formulation of claim 10, further comprising an ethanol component.

13. The aqueous formulation of claim 12, wherein the ethanol component is approximately 0.001% by mass to approximately 10% by mass of the formulation.

14. The aqueous formulation of claim 10, further comprising a surfactant component, wherein the surfactant component includes one or more different surfactants.

15. The aqueous formulation of claim 14, wherein the surfactant component includes one or more of polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monolaurate, lecithin, and a poloxamer.

16. The aqueous formulation of claim 14, wherein the surfactant component is approximately 0.001% by mass to approximately 10% by mass of the formulation. The aqueous formulation of claim 10, further comprising an ethanol component and a surfactant component. A method of preparing an aqueous formulation for aerosolizing and inhaling using electronic devices comprising: mixing a nicotine component and an acid component to form a first mixture; separately mixing a menthol component and a saline component to form a second mixture; and mixing the first mixture and the second mixture to form a target aqueous formulation. A method of preparing an aqueous formulation for aerosolizing and inhaling using electronic devices comprising:

(a) mixing a nicotine component and an acid component to form a first mixture;

(b) separately mixing a menthol component and an ethanol component to form a second mixture;

(c) mixing a saline component with the second mixture to form a third mixture; and

(d) mixing the first mixture and the third mixture to form a target aqueous formulation. A method of preparing an aqueous formulation for aerosolizing and inhaling using electronic devices comprising:

(a) mixing a nicotine component and an acid component to form a first mixture;

(b) mixing a saline component with the first mixture to form a second mixture;

(c) separately mixing a menthol component, an ethanol component, and a surfactant component to form a third mixture; and

(d) mixing the second mixture and the third mixture to form a target aqueous formulation.