Microemulsion particle formulations and microemulsion particle-fortified beverages

Abstract

Microemulsion particle formulations disclosed herein may be included in beverages, for example energy drinks. Disclosed microemulsion particle formulations comprise one or more microemulsion particle and high water content, wherein the one or more microemulsion particle comprises a payload component, a fatty component, a surfactant component, an antioxidant component, and a stabilizing component.

Description

MICROEMULSION PARTICLE FORMULATIONS AND MICROEMULSIONPARTICLE-FORTIFIED BEVERAGESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 617,392, filed January 3, 2024; U.S. Provisional Patent Application No. 63 / 554,093, filed February 15, 2024; U.S. Provisional Patent Application No. 63 / 564,942, filed March 13, 2024; and U.S. Provisional Patent Application No. 63 / 573,404, filed April 2, 2024; the title of each of which is “Microemulsion Particle Formulations And Microemulsion Particle-Fortified Beverages” and the content of each of which is incorporated herein by reference in its entirety.BACKGROUND

[0002] Inclusion of various hydrophobic and / or hydrophilic compounds in beverages for human ingestion has been difficult to achieve because of their poor stability after short term and / or long-term storage. Conventional methods of preserving the stability of compounds susceptible to degradation can negatively affect characteristics (e.g., turbidity, taste, viscosity, etc.) of the beverage to which they are added. Moreover, compounds ingested by a subject may be degraded before being absorbed in the gastrointestinal tract of a human subject following ingestion. Thus, there is a need to develop formulations that improve the storage stability of compounds in beverages and / or the sustained release / bioavailability of compounds when ingested. Accordingly, the present disclosure provides microemulsion particle formulations, fortified beverages comprising the same, and methods of producing the same to address this unmet need.SUMMARY

[0003] The present disclosure provides a variety of technologies relating to incorporating payload components into beverages. The present disclosure specifically provides technologies for incorporating payload components into microemulsion particle formulations, which are combined with aqueous solutions (i.e., base beverages) to provide ingestible (specifically, drinkable) fortified beverages with one or more beneficial or otherwise desirable attributes.

[0004] In some embodiments, provided technologies identify the source of one or more problems with conventional approaches to incorporating certain payloads into beverages, and solve such problems.

[0005] Alternatively or additionally, in some embodiments, provided technologies achieve one or more performance attributes not previously demonstrated to be feasible.

[0006] The present disclosure documents success of provided technologies with a variety of different payloads (specifically including each of lutein, Vitamin D2, Vitamin B12, and caffeine) in microemulsion particle formulations prepared from various components (e g., fatty component, surfactant component and, optionally, one or more antioxidant and / or stabilizing components). The present disclosure demonstrates feasibility of achieving results documented herein, and sufficiently establishes proof of concept that a skilled person, reading the present disclosure, will immediately appreciate that its teachings are not limited to the exemplified components or recipes.

[0007] To give but a few examples of insights provided by the present disclosure, it is demonstrated herein that microemulsion technologies may be particularly useful for introducing and / or maintaining payload(s) in beverage(s). Among other things, the present disclosure demonstrates that microemulsion technologies as described herein can achieve long term stable maintenance of payload(s) of interest, in some embodiments in diverse beverages (e.g., in beverages of different pHs and / or including different components) and / or may achieve desirable release characteristics over time. The present disclosure further documents that such release characteristics are stable even after storage of a provided microemulsion particle formulation (containing a payload of interest) in a beverage (including, for example, a sports drink or a soda, e.g., a carbonated soda).

[0008] Some embodiments of provided technologies may utilize payload in a solid form. However, some embodiments of provided technologies encompass a recognition that in certain contexts microemulsion particle formulations are desirably prepared and / or maintained in liquid form, or at least without component(s) (e.g., payload component(s) in a solid form). The present disclosure appreciates that other reports describe technologies where, for example, explicit drying and / or isolation steps are performed in order to provide a payload component in a solid form, which may then be incorporated into an emulsion (see, for example, WO2022266442,which describes preparation of caffeine:tannic acid complexes by drying or otherwise isolating solid precipitates and, in some embodiments, including them in an emulsion composition).

[0009] The present disclosure teaches that, in certain embodiments, steps to affirmatively generate and / or isolate solid form payload component(s) need not be, and in fact, surprisingly, desirably should not be performed. Indeed, the present disclosure notes that certain reports of solid-payload emulsions (see, for example, WO2022266442) describe such emulsions as encapsulating payload such that its concentration in the emulsion is “stable” relative to that in the beverage into which the emulsion is incorporated, and yet document significant changes in payload (in this case, caffeine) concentration in the beverage over time, including changes that reflect both release of payload from the emulsion into the beverage, and extraction of payload component(s) from the beverage over time, inducing a significant change in level (close to 3 fold).

[0010] The present disclosure, by contrast, demonstrates desirable stability of provided microemulsion particle formulations, including of desirable release characteristics. For example, the present disclosure documents stability (including absence of payload release) of provided microemulsion particle formulations, even after combination with, and storage in, base beverages. The present disclosure further demonstrates extended release of payload over a period of hours after simulated ingestion of a fortified beverage, and maintenance of such release characteristics after storage of such fortified beverage (i .e., storage of a provided microemulsion particle formulation in a base beverage).

[0011] Without wishing to be bound by any particular theory, the present disclosure proposes that avoiding solid-phase payload components may permit preparation of more tunable microemulsion particle formulations, for example facilitating bespoke design of such formulations for inclusion in particular beverage(s) of interest.

[0012] Yet, interestingly, the present disclosure also demonstrates that certain provided microemulsion particle formulations are characterized by stable attributes when combined with various different base beverages (e.g., with different pHs and / or other different components (e.g., flavors, fragrances, vitamins, stimulants (e.g., caffeine) and / or levels and / or combinations thereof).

[0013] The present disclosure further demonstrates that, in certain embodiments, provided formulations have beneficial particle size characteristics (e.g., average size and / or particles size distribution characteristics) so that among other things, combination of provided microemulsion particle formulations with base beverages does not negatively impact aspects of the beverages, such as turbidity or other visual characteristics. Moreover, the present disclosure documents that such particle size characteristics are maintained over time, including after combination with, and storage in, such base beverage.

[0014] The present disclosure provides formulations including one or more microemulsion (ME) particles, and fortified beverages incorporating said one or more formulations, wherein the one or more microemulsion particles incorporate a payload component, a fatty component, a surfactant component, an antioxidant component, and a stabilizing component. Exemplary formulations of the present disclosure provide improved stability / recovery of the payload component, improved solubility / reduced turbidity of microemulsion particles when added to a base beverage, delayed release of the payload component when added to a base beverage, and / or delayed release of the payload component in the gastrointestinal tract of a subject that ingests the formulation.

[0015] In one aspect, the present disclosure is directed to a microemulsion particle composition comprising an oily phase comprising fatty acid particles that are dispersed within an aqueous liquid phase. In some embodiments, the oily phase further comprises a payload component, a surfactant component and, optionally one or both of an antioxidant component and a stabilizing component. In some embodiments, the payload component is or comprises caffeine and a complexing agent, in a molar ratio greater than 3: 1 caffeine:complexing agent.

[0016] In some embodiments, the complexing agent is tannic acid, a catechin, epigallocatechin-3 -gallate, gallic acid or a derivative thereof, or an alagi tannin.

[0017] In some embodiments, the microemulsion particle composition is characterized by an average particle size or particle size distribution such that combination of the microemulsion particle composition with a base beverage does not materially change turbidity of the base beverage.

[0018] In some embodiments, the microemulsion particle composition characterized in that its average particle size or particle size distribution remains stable upon combination with a base beverage.

[0019] In some embodiments, the average particle size or particle size distribution remains stable throughout storage for a period of time at least eight (8) weeks long after combination with a base beverage.

[0020] In some embodiments, the microemulsion particle composition being characterized in that one or more of: its average particle size, its particle size distribution, and its payload release characteristics, remains reasonably stable throughout storage for a period of time at least eight (8) weeks long after combination with a base beverage.

[0021] In another aspect, the present disclosure is directed to formulations (e.g., microemulsion particle formulations) comprising one or more microemulsion particles and at least 79 wt% water, wherein the one or more microemulsion particles comprises: 0.01 wt% to 0.13 wt% of a payload component; 0.1 wt% to 2 wt% of a fatty component; 12 wt% to 20 wt% of a surfactant component; 0.1 wt% to 2 wt% of an antioxidant component; and 0.1 wt% to 4 wt% of a stabilizing component.

[0022] In some embodiments, payload components comprise lutein, vitamin D, zeaxanthin, vitamin A, caffeine, vitamin Bl 2, creatine, creatine ethyl ester, creatine phosphate, tannic acid, theaflavin, theaflavin gallate, thearubigins, ellagitannins, catechins, epigallocatechin gallate, gallic acid and its alkyl esters, glucose, curcurmin, quercetin, rutin, naringenin, fatty acids, a nutritive and / or bioactive peptide, a feruloylated arabinoxylan-enriched fiber, heat- treated whey protein isolate, sodium caseinate, collagen, gelatin, rice bran, wheat bran, resistant corn dextrin, resistant potato dextrin or a combination thereof.

[0023] In some embodiments, fatty components comprise soybean oil, corn oil, safflower oil, olive oil, stearine, beeswax, canola oil, mineral oil, sunflower oil, glyceryl tripalmitate, medium chain triglycerides, coconut oil, or combination thereof.

[0024] In some embodiments, surfactant components comprise polysorbate 80, polysorbate 60, saponin, coco glucoside, 12-hydroxystearic acid, palmitic acid, stearic acid, polyvinylpyrrolidone, propylene glycol, polygly ceryl- 10 dicaprate / dicaprylate, polyglyceryl- 10laurate, polyglyceryl- 10 caprate / caprylate, sucrose monolaurate, sucrose monopalmitate, sucrose monostearate, oat polar lipid fraction, or a combination thereof.

[0025] In some embodiments, antioxidant components comprise a-tocopherol, rosemary oil, citric acid, glutathione, astaxanthin, butylated hydroxyanisole, butylated hydroxytoluene, gum guaiac, or combination thereof.

[0026] In some embodiments, stabilizing components comprise buttermilk, stearyl alcohol, glycerol, citric acid, lecithin, choline bicarbonate, xanthan gum, tara gum, konjac gum, tragacanth gum, guar gum, cationic guar gum, chitosan, spermidine-rich wheat germ extract, cetyltrimethylammonium bromide, sodium dioctylsulfosuccinate, sodium lauryl sulfate, starch phosphates, tartaric acid esters of mono- and di-glycerides, metatartaric acid, whey protein isolate, casein, gum arabic, sodium alginates, maltose, pectins, carrageenans, iron(III) sulfate, iron(III) hydroxide, P-sitosterol, cholesterol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, tetradecanol, octadecanol, hexadecanol, carboxymethyl cellulose, sterol, stanol, cardiolipin, or combination thereof.

[0027] In some embodiments, one or more microemulsion particles comprise a diameter in a range from 5 nm to 150 nm, 10 nm to 125 nm, 20 nm to 100 nm, or 25 nm to 75 nm.

[0028] In some embodiments, a microemulsion formulation provided and / or utilized herein is characterized by, for example, an average particle size (e.g., average particle diameter) within a range of about 5 nm to about 250 nm. In some embodiments, such average particle size is within a range of about 5 nm to about 50 nm. In some embodiments, such average particle size is within a range of about 10 nm to about 100 nm. In some embodiments, such average particle size is within a range of about 25 nm to about 150 nm. In some embodiments, such average particle size is within a range of about 50 nm to about 250 nm.

[0029] In some embodiments, a microemulsion formulation provided and / or utilized in accordance with the present disclosure is characterized by, for example, a poly dispersity index within a range of about 0.0 to about 0.2.

[0030] In another embodiment, the present disclosure is directed to beverages that are referred to as fortified beverages because they comprise a disclosed formulation and a base beverage. Thus, the base beverage is fortified by combination with the provided formulation.

[0031] In some embodiments, fortified beverages comprise an energy drink, water, nutrient-fortified water, carbonated drink, coffee, tea, juice, milk, milk alternative, or baby formula.

[0032] In some embodiments, fortified beverages comprise 0.5 % w / v to 2 % w / v of payload components.

[0033] In some embodiments, fortified beverages are characterized by a turbidity no greater than 600 NTU, no greater than 575 NTU, no greater than 550 NTU, no greater than 525 NTU, no greater than 500 NTU, no greater than 400 NTU, no greater than 300 NTU, no greater than 200 NTU, no greater than 100 NTU, or no greater than 50 NTU.

[0034] In some embodiments, fortified beverages comprise disclosed formulations (e.g, microemulsion particle formulations) where the microemulsion particles are at a concentration of 0.001 to 0.075 mg / ml, 0.01 to 0.075 mg / ml, 0.02 mg / ml to 0.075 mg / ml, 0.04 mg / ml to 0.075 mg / ml, or 0.06 mg / ml to 0.075 mg / ml of energy drink.

[0035] In some embodiments, at least 80% of payload components are recoverable from fortified beverages after 8 weeks of storage. Thus, in some embodiments, a provided fortified beverage that was fortified with a payload-containing formulation as described herein is characterized in that (a) it has been stored for a period of time that is at least 8 weeks long (i.e., since combination of the payload-containing formulation with the base beverage); and (b) at least 80% of the payload components present at the time of combination are recoverable from the fortified beverage after the period of storage.

[0036] In some embodiments, at least 75% of payload components are recoverable from fortified beverages after 16 weeks of storage. Thus, in some embodiments, a provided fortified beverage that was fortified with a payload-containing formulation as described herein is characterized in that (a) it has been stored for a period of time that is at least 16 weeks long (i.e., since combination of the payload-containing formulation with the base beverage); and (b) at least 75% of the payload components present at the time of combination are recoverable from the fortified beverage after the period of storage.

[0037] In another aspect, the present disclosure is directed to a fortified beverage composition comprising an aqueous liquid phase and a fatty particle phase. In someembodiments, at least the particle phase comprises a payload component. In some embodiments, the fortified beverage composition has been stored for a period of time that is at least about 8 weeks long, the payload component is present in the particle phase in an amount reasonably comparable to that at which it was present prior to such storage, and the fortified beverage composition is characterized in that, when it is contacted with simulated gastric fluid, the payload component is released into the simulated gastric fluid so that the payload component is released into the simulated gastric fluid over a period of up to 12 hours.

[0038] In some embodiments, the period of time is about 8 weeks and the amount of payload component present in the particle phase is at least 80% of that present prior to such storage.

[0039] In some embodiments, the period of time is about 16 weeks and the amount of payload component present in the particle phase is at least 75% of that present prior to such storage.

[0040] In another aspect, the present disclosure is directed to a fortified beverage composition comprising an aqueous liquid phase and a fatty particle phase. In some embodiments, each of the aqueous liquid phase and the fatty particle phase includes caffeine and the total caffeine in the fortified beverage composition is within a range of 30 mg / L to 600 mg / L; at least 40% of the caffeine is present in the fatty particle phase; and the fortified beverage composition is characterized in that, when it is contacted with simulated gastric fluid, the payload component is released into the simulated gastric fluid so that the payload component is released into the simulated gastric fluid over a period of about 4 hours to about 6 hours.

[0041] In some embodiments, fortified beverage composition has been stored for a period of time that is at least 8 weeks.

[0042] The present disclosure provides technologies for characterization and / or production of microemulsion particle formulations as described herein, and / or beverages (i.e., fortified beverages) that contain them.

[0043] For example, in another embodiment, the present disclosure is directed to methods for fortifying a beverage, e g., methods comprising: i) providing a microemulsion particle formulation as described herein; and ii) combining the microemulsion particleformulation with the beverage to produce a fortified beverage; as described herein, in many embodiments, a microemulsion particle formulation utilized in such combination comprises one or more microemulsion particles and at least 79 wt% water, and the one or more microemulsion particles comprises: 0.01 wt% to 0.13 wt% of a payload component; 0.1 wt% to 2 wt% of a fatty component; 12 wt% to 20 wt% of a surfactant component; 0.1 wt% to 2 wt% of an antioxidant component; and 0.1 wt% to 4 wt% of a stabilizing component.

[0044] In some embodiments, providing a microemulsion particle formulation comprises: i) preparing an aqueous phase; ii) preparing an oil phase; and iii) combining the aqueous and the oil phases so that the microemulsion particle formulation, comprising a plurality of microemulsion particles is produced.

[0045] In some embodiments, i) preparing an aqueous phase comprises mixing water and an antioxidant component; and ii) preparing an oil phase comprises mixing a payload component, an oil component, a surfactant component, and a stabilizing component.

[0046] In some embodiments, payload components comprise lutein, vitamin D, zeaxanthin, vitamin B 12, or a combination thereof.

[0047] In some embodiments, i) preparing an aqueous phase comprises mixing water, a payload component, and an antioxidant component; and ii) preparing an oil phase comprises mixing an oil component, a surfactant component, and a stabilizing component.

[0048] In some embodiments, payload components comprise caffeine.

[0049] In another aspect, the present disclosure is directed to a formulation comprising one or more microemulsion particles and at least 73 wt% water. In some embodiments, the one or more microemulsion particles comprises: 2 wt% to 5 wt% of a payload component; 2 wt% to 8 wt% tannic acid; 0.1 wt% to 4 wt% of a fatty component; 12 wt% to 16 wt% of a surfactant component; 0.1 wt% to 2 wt% of an excipient component; and 0.1 wt% to 2 wt% of a stabilizing component.

[0050] In some embodiments, the payload comprises caffeine, wherein the surfactant comprises polysorbate 80. In some embodiments, the stabilizing component comprises xanthan gum.

[0051] In some embodiments, the excipient component comprises at least one of alginate, 210S, carrageenan, maltose, and pectin.

[0052] In some embodiments, the payload comprises caffeine. In some embodiments, the formulation comprises the payload component and tannic acid in a combined weight percent in a range from 8 wt% to 9 wt%.

[0053] In another aspect, the present disclosure is directed to a formulation comprising one or more microemulsion particles and at least 67 wt% water. In some embodiments, the one or more microemulsion particles comprises: 0.01 wt% to 0.15 wt% of a payload component; 2 wt% to 6 wt% of ethanol; 2 wt% to 6 wt% of isoamyl acetate; and 5 wt% to 12 wt% of Kolliphor EL.

[0054] In some embodiments, the payload comprises free vitamin B 12 powder.

[0055] In another aspect, the present disclosure is directed to a method of evaluating payload release from a microemulsion formulation, the method comprising: adding a first mixture of the microemulsion, water and simulated gastric fluid (SGF) to a dialysis device; sampling the mixture after multiple periods of time; dividing each sample into multiple replicates, each replicate of the multiple replicates being disposed within a tube separate from tubes containing other replicates of the multiple replicates; adding dichloromethane (DCM) to each tube; capping each tube; vortexing each tube for a first predetermined period of time; centrifuging each tube for a second predetermined period of time at a predetermined rotational speed, thereby forming a top layer and a bottom layer of the mixture; separating the top layer from the bottom layer of each replicate of each sample; and performing high performance liquid chromatography (HPLC) of the bottom layer of each replicate of each sample to analyze release of the pay load from each sample.

[0056] In some embodiments, the first predetermined period of time comprises 8-10 seconds. In some embodiments, the second predetermined period of time comprises 4-6 minutes. In some embodiments, the rotational speed comprises a rotational speed in a range from about 20,000 ref to about 21 ,500 ref

[0057] In some embodiments, performing high performance liquid chromatography (HPLC) comprises using a diode-array detector to measure UV absorbance at a wavelength in arange from about 250 nm to about 450 nm at a column temperature in a range from about 15 °C to about 45 °C.

[0058] In some embodiments, the payload comprises lutein, caffeine, vitamin D2 or vitamin B l 2.

[0059] In some embodiments, the microemulsion comprises a microemulsion particle composition.

[0060] In another aspect, the present disclosure is directed to a method for fortifying a beverage, the method comprising: i) providing a microemulsion particle formulation; and ii) mixing the microemulsion particle formulation with the beverage to produce a fortified beverage. In some embodiments, the microemulsion particle formulation comprises one or more microemulsion particles and at least 79 wt% water, and the one or more microemulsion particles comprises: 0.01 wt% to 0.13 wt% of a payload component; 0.1 wt% to 2 wt% of a fatty component; 12 wt% to 20 wt% of a surfactant component; 0.1 wt% to 2 wt% of an antioxidant component; and 0.1 wt% to 4 wt% of a stabilizing component. In some embodiments, the resulting fortified beverage composition is characterized in that, when it is contacted with simulated gastric fluid, the payload component is released into the simulated gastric fluid so that the payload component is released into the simulated gastric fluid over a period of about 4 hours to about 12 hours.

[0061] Any two or more of the features described in this specification, including in this summary section, may be combined to form implementations not specifically explicitly recited as a combination in this specification.BRIEF DESCRIPTION OF THE DRAWING

[0062] Figures of the Drawing are presented herein for illustration purposes, not for limitation. The foregoing and other objects, aspects, features, and advantages of the disclosure will become more apparent and may be better understood by referring to the following description taken in conjunction with the accompanying drawings, in which:

[0063] FIG. 1 is a schematic of an exemplary microemulsion particle according to illustrative embodiments of the present disclosure;

[0064] FIG. 2 is a flow chart showing an exemplary manufacturing method for preparing microemulsion particles, formulations, and fortified beverages according to illustrative embodiments of the present disclosure;

[0065] FIG. 3A - FIG. 3B are plots of particle diameter size (FIG. 3A) and turbidity (FIG. 3B) of microemulsion particle formulations and non-microemulsion particle formulations according to illustrative embodiments of the present disclosure;

[0066] FIG. 4A - FIG. 4B are plots of particle diameter size (FIG. 4A) and turbidity (FIG. 4B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) according to illustrative embodiments of the present disclosure;

[0067] FIG. 4C - FIG. 4D are photographs of samples of water including microemulsion particle formulations at day 0 (FIG. 4C) and day 30 (FIG. 4D) according to illustrative embodiments of the present disclosure;

[0068] FIG. 5A - FIG. 5B are plots of particle diameter size (FIG. 5A) and turbidity (FIG. 5B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) according to illustrative embodiments of the present disclosure;

[0069] FIG. 5C - FIG. 5D are photographs of samples of a Red Bull™ energy drink including microemulsion particle formulations at day 0 (FIG. 5C) and day 30 (FIG. 5D) according to illustrative embodiments of the present disclosure;

[0070] FIG. 6A - FIG. 6B are plots of particle diameter size (FIG. 6A) and turbidity (FIG. 6B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) according to illustrative embodiments of the present disclosure;

[0071] FIG. 6C - FIG. 6D are photographs of samples of a Monster™ energy drink including microemulsion particle formulations at day 0 (FIG. 6C) and day 30 (FIG. 6D) according to illustrative embodiments of the present disclosure;

[0072] FIG. 7A - FIG. 7B are plots of particle diameter size (FIG. 7A) and turbidity (FIG. 7B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) according to illustrative embodiments of the present disclosure;

[0073] FIG. 7C - FIG. 7D are photographs of samples of a Rockstar™ energy drink including microemulsion particle formulations at day 0 (FIG. 7C) and day 30 (FIG. 7D) according to illustrative embodiments of the present disclosure;

[0074] FIG. 8A - FIG. 8B are plots of particle diameter size (FIG. 8A) and turbidity (FIG. 8B) of microemulsion particle formulations and non-microemulsion particle formulations (“Omni active”) v. their concentration in a Rockstar™ energy drink, according to illustrative embodiments of the present disclosure;

[0075] FIG. 8C - FIG. 8D are photographs of samples of a Rockstar™ energy drink including non-microemulsion particle formulations (FIG. 8C) and microemulsion particle formulations (FIG. 8D) at varying concentrations according to illustrative embodiments of the present disclosure;

[0076] FIG. 9A is a plot presenting stability of lutein as a payload component in microemulsion particle formulations included in a Monster™ energy drink according to illustrative embodiments of the present disclosure;

[0077] FIG. 9B shows photographs of samples of a plain Monster™ energy drink (left panel), a Monster™ energy drink including a microemulsion particle formulation (middle panel), and a Monster™ energy drink including a non-microemulsion particle formulation (right panel) according to illustrative embodiments of the present disclosure;

[0078] FIG. 9C is a plot presenting stability of lutein as a payload component in both microemulsion particle formulations and non-microemulsion particle formulations (“Omniactive”) included in a Monster™ energy drink according to illustrative embodiments of the present disclosure;

[0079] FIG. 9D shows photographs of samples of a plain Monster™ energy drink (left panel), a Monster™ energy drink including a non-microemulsion particle formulation (centerleft panel), a Monster™ energy drink including a microemulsion particle formulation (centerright panel and right panel) according to illustrative embodiments of the present disclosure;

[0080] FIG. 9E - FIG. 9H are plots presenting stability of lutein as a payload component in both microemulsion particle formulations and non-microemulsion particleformulations (Omniactive) included in a Monster™ energy drink according to illustrative embodiments of the present disclosure;

[0081] FIG. 10A is a plot presenting stability of lutein as a payload component in both microemulsion particle formulations and non-microemulsion particle (Omniactive) formulations included in a Rockstar™ energy drink according to illustrative embodiments of the present disclosure;

[0082] FIG. 10B shows photographs of samples of a plain Rockstar™ energy drink (left panel), a Rockstar™ energy drink including a non-microemulsion particle formulation (Omniactive; center-left panel), a Rockstar™ energy drink including a microemulsion particle formulation (center-right panel and right panel) according to illustrative embodiments of the present disclosure;

[0083] FIG. 10C - FIG. 10D are plots presenting stability of lutein as a payload component in both microemulsion particle formulations and non-microemulsion particle formulations (Omniactive) included in a Rockstar™ energy drink according to illustrative embodiments of the present disclosure;

[0084] FIG. 11A is a plot presenting stability of lutein as a payload component in microemulsion particle formulations according to illustrative embodiments of the present disclosure;

[0085] FIG. 11B is a photograph of samples of microemulsion particle formulations according to illustrative embodiments of the present disclosure;

[0086] FIG. 11C is a plot presenting stability of lutein as a payload component in microemulsion particle formulations according to illustrative embodiments of the present disclosure;

[0087] FIG. 12A - FIG. 12C are plots presenting stability performance characteristics of microemulsion particle formulations comprising lutein as a payload component when formulations are included in water (FIG. 12A), oatmilk (FIG. 12B), and Oatly™ beverage (FIG. 12C);

[0088] FIG. 13A - FIG. 13B are plots presenting stability performance characteristics of microemulsion particle formulations comprising vitamin D2 as a payload component when formulations are included in water (FIG. 13A) and oatmilk (FIG. 13B);

[0089] FIG. 14A - FIG. 14C are plots presenting stability performance characteristics of microemulsion particle formulations comprising vitamin B 12 as a payload component when formulations are included in water (FIG. 14A), oatmilk (FIG. 14B), and Oatly™ beverage (FIG. 14C);

[0090] FIG. 15A - FIG. 15C are plots presenting release performance characteristics of microemulsion particle formulations comprising caffeine as a payload component according to illustrative embodiments of the present disclosure;

[0091] FIG. 16A - FIG. 16B are plots presenting release performance characteristics of microemulsion particle formulations comprising caffeine as a payload component when formulations are stored for 6 weeks with exposure to light in a Monster™ energy drink according to illustrative embodiments of the present disclosure;

[0092] FIG. 17A - FIG. 17B are plots presenting release performance characteristics of microemulsion particle formulations comprising caffeine as a payload component when formulations are stored for 6 weeks in a Pepsi soft drink according to illustrative embodiments of the present disclosure;

[0093] FIG. 18A - FIG. 18B are plots presenting release performance characteristics of microemulsion particle formulations comprising caffeine as a payload component when formulations are stored for 3 weeks in a Coca-Cola soft drink according to illustrative embodiments of the present disclosure; and

[0094] FIG. 19A - FIG. 19B are plots presenting release performance characteristics of microemulsion particle formulations comprising caffeine as a payload component when formulations are stored for 4 weeks in a Monster™ energy drink according to illustrative embodiments of the present disclosure.DEFINITIONS

[0095] As described in the present disclosure, the following terms will be employed, and are defined as indicated below.

[0096] Unless defined otherwise, technical and scientific terms used herein have the same meaning as is commonly understood to which the claimed subject matter belongs. In the event that there are a plurality of definitions for terms herein, those in this section prevail.

[0097] It is to be understood that the general description and the detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed. In this application, the use of the singular includes the plural unless specifically stated otherwise. It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. In this application, the use of “or” means “and / or” unless stated otherwise. Furthermore, use of the term “including” as well as other forms, such as “include”, “includes,” and “included,” is not limiting.

[0098] Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” Further, headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed invention.

[0099] Definition of standard chemistry terms may be found in reference works, including but not limited to, Carey and Sundberg “Advanced Organic Chemistry 4th Ed.” Vols. A (2000) and B (2001), Plenum Press, New York.

[0100] As used herein, the term “about” or “approximately” means within 10%, preferably within 10%, and more preferably within 5% of a given value or range.

[0101] Ambient: The term “ambient”, as used herein, refers to a typical indoor (e.g., climate-controlled) temperature, usually within a range of about 18° C to about 32° C, and / or typical indoor (e g., climate-controlled) humidity, usually within a range of about 30% to 50%. In some embodiments, ambient temperature is within a range of about 20° C to about 30° C. In some embodiments, ambient temperature is 25±5° C. In some embodiments, ambient temperature is approximately 21° C. In some embodiments, ambient temperature is 18° C. In some embodiments, ambient temperature is 19° C. In some embodiments, ambient temperature is 20° C. In some embodiments, ambient temperature is 21° C. In some embodiments, ambient temperature is 22° C. In some embodiments, ambient temperature is 23° C. In some embodiments, ambient temperature is 24° C. In some embodiments, ambient temperature is 25°C. Tn some embodiments, ambient temperature is 26° C. In some embodiments, ambient temperature is 27° C. In some embodiments, ambient temperature is 28° C. In some embodiments, ambient temperature is 29° C. In some embodiments, ambient temperature is 30° C. In some embodiments, ambient may be used to describe outdoor conditions, and may include temperatures ranging from about 15° C to about 40° C, or from about 25° C to about 40° C. In some embodiments, ambient humidity is within a range of about 35% to about 45%. In some embodiments, ambient temperature is 35%. In some embodiments, ambient temperature is 36%. In some embodiments, ambient temperature is 37%. In some embodiments, ambient temperature is 38%. In some embodiments, ambient temperature is 39%. In some embodiments, ambient temperature is 40%. In some embodiments, ambient temperature is 41%. In some embodiments, ambient temperature is 42%. In some embodiments, ambient temperature is 43%. In some embodiments, ambient temperature is 44%. In some embodiments, ambient temperature is 45%.

[0102] Beverage: As used herein, the term “beverage” is used to refer to a potable liquid (e.g., that can be ingested, swallowed, drunk, or consumed by a person or animal without material risk to the person or animal). For example, a beverage can be or include an energy drink, water, nutrient-fortified water, carbonated drink, coffee, tea, juice, milk, milk alternative, or baby formula. In some embodiments, a “beverage” may be or comprise a formulation of the present disclosure in liquid form.

[0103] Biocompatible: As used herein, the term “biocompatible” is used to describe a characteristic of not causing significant detectable harm to living tissue when placed in contact therewith e.g., in vivo. In certain embodiments, materials are “biocompatible” if they are not significantly toxic to cells, e.g., when contacted therewith in a relevant amount and / or under relevant conditions such as over a relevant period of time. In certain embodiments, materials are “biocompatible” if their addition to cells in vitro results in less than or equal to 20% cell death, and / or their administration in vivo does not induce significant inflammation or other adverse effects.

[0104] Comparable: As used herein, the term “comparable” refers to two or more agents, entities, situations, sets of conditions, etc., that may not be identical to one another but that are sufficiently similar to permit comparison therebetween so that one skilled in the art will appreciate that conclusions may reasonably be drawn based on differences or similaritiesobserved. Tn some embodiments, comparable sets of conditions, circumstances, individuals, or populations are characterized by a plurality of substantially identical features and one or a small number of varied features. Those of ordinary skill in the art will understand, in context, what degree of identity is required in any given circumstance for two or more such agents, entities, situations, sets of conditions, etc. to be considered comparable. For example, those of ordinary skill in the art will appreciate that sets of circumstances, individuals, or populations are comparable to one another when characterized by a sufficient number and type of substantially identical features to warrant a reasonable conclusion that differences in results obtained or phenomena observed under or with different sets of circumstances, individuals, or populations are caused by or indicative of the variation in those features that are varied.

[0105] Cryoprotectant: As used herein the term “cryoprotectant” refers to a chemical or compound that is used to prevent the formation of ice crystals during the supercooling of a water containing sample.

[0106] Degradation: As used herein, the term “degradation” refers to a change in chemical structure and often involves breakage of at least one chemical bond. To say that a chemical compound is degraded typically means that the chemical structure of the chemical compound has changed (e.g., a chemical bond is broken). Common mechanisms of degradation include, for example, oxidation, hydrolysis, isomerization, fragmentation, or a combination thereof.

[0107] Diameter: As used herein, the term “diameter” is used to refer to the longest distance from one end of a particle to another end of the particle. Those skilled in the art will appreciate that a variety of techniques are available for use in characterizing particle diameters (i.e., particle sizes). In some instances, for example, size of particles (e.g., diameter of particles) can be measured by a Coulter Counter. In some instances, for example, size of particles (e.g., diameter of particles) can be measured by a Malvern Mastersizer. In some embodiments, a population of particles is characterized by an average size (e.g., D[3,2], D[4,3], etc.) and / or by particular characteristics of size distribution (e.g., absence of particles above or below particular sizes [e.g., DvlO, Dv20, Dv30, Dv40, Dv50, Dv60, Dv70, Dv80, Dv90, Dv99, etc ], a unimodal, bimodal, or multimodal distribution, etc.).

[0108] Dispersity: As used herein, the term “dispersity” is used to refer to the breadth of particle size distribution relative to the average particle size. In some instances, for example, size of particles (e.g., diameter of particles) can be measured by a Coulter Counter. In some instances, for example, size of particles (e.g., diameter of particles) can be measured by a Malvern Mastersizer. In some embodiments, the population of particles is characterized by, for example, an average size (e.g., Dv50) and, for example, a corresponding standard deviation. In some instances, the dispersity of a population of particles refers to double (e.g., 2-fold) the ratio of standard deviation (e.g., G) to average particle diameter (e.g., Dv50).

[0109] Encapsulated: As used herein, the term “encapsulated” is used to refer to a characteristic of being physically associated with, and in some embodiments partly or wholly covered or coated. For example, in many embodiments of the present disclosure, a payload component (e.g., a microbe component and / or a nutrient component) is described as being encapsulated by a polymer component.

[0110] HLB As used herein, the term “HLB” is used to refer to the hydrophilic lipophilic balance that is an inherent property of, for example, a nonionic surfactant. In some instances, the HLB value of a given non-ionic surfactant is obtained from a commonly accessible tabular source. In some embodiments, non-ionic surfactants characterized as having a low HLB value (e.g., < 8) are compatible emulsifiers for lipid systems. In some embodiments, nonionic surfactants characterized as having a high HLB value (e g., >15) are compatible emulsifiers for aqueous systems. In some embodiments, non-ionic surfactants characterized as having an intermediate HLB value (e.g., >8 and <15) are compatible emulsifiers with both lipid and aqueous systems.

[0111] Homogenous: As used herein, the term “homogenous” means of substantially uniform structure and / or composition throughout.

[0112] Hydrophobic: As used herein, the term “hydrophobic” is used to refer to the propensity of a material to reject association, chemically and / or physically, with water. In some instances, a material characterized as being hydrophobic is biologically derived and / or synthetically derived. In some instances, a material characterized as being hydrophobic is a lipid, protein, and / or carbohydrate. In some instances, a material characterized as being hydrophobic is a polymer and / or small molecule. Alternatively, or additionally, in some embodiments,composites, mixtures, blends, or super-structures of several materials are collectively referred to as hydrophobic based on their observed propensity to reject association, chemically and / or physically, with water.

[0113] Hydrophilic: As used herein, the term “hydrophilic” is used to refer to the propensity of a material to associate, chemically and / or physically, with water. In some instances, a material characterized as being hydrophilic is biologically derived and / or synthetically derived. In some instances, a material characterized as being hydrophilic is a protein, and / or carbohydrate. In some instances, a material characterized as being hydrophilic is a polymer and / or small molecule. Alternatively, or additionally, in some embodiments, composites, mixtures, blends, or super-structures of several materials are collectively referred to as hydrophilic based on their observed propensity to associate, chemically and / or physically, with water.

[0114] Incorporation: As used herein, the term “incorporation” is used to refer to a characteristic of being physically associated with, and in some embodiments, dispersed within, embedded within, or mixed in a bulk material (e.g., a lipid component).

[0115] Layer: As used herein, the term “layer” typically refers to a material disposed above or below a distinguishable material. In some embodiments, a particular entity or preparation (e.g., particle preparation) is described as “layered” if it is prepared via a process in which a first material is laid down and then a second material is applied atop or underneath the first material(e.g., as by dipping or spraying, etc.); in some such embodiments, physical or chemical distinctness of layers may be maintained over time, whereas in some such embodiments, physical or chemical distinctness of layers may decay over time, at least at layer interface(s). Alternatively or additionally, in some embodiments, a particular sample or preparation may be described as layered, independent of its mode of preparation, so long as at a particular point in time and / or using a particular mode of assessment, distinct materials can be identified in a layered structure. In some embodiments, a “layered” particle may include one or more layers that wholly encapsulate a material below. In some embodiments, a “layered” particle may include one or more layers that does not wholly encapsulate a material below. In some embodiments, at least one layer of a layered preparation is or comprises a polymer, e.g., a hydrophobic polymer or hydrophilic polymer. In some embodiments, each layer of a layeredpreparation is or comprises a polymer, e g., a pH responsive polymer or a temperature- responsive polymer.

[0116] Lipid: As used herein, the term “lipid” is used to refer to a class of chemical structures characterized as hydrophobic materials. In some instances, a lipid material is derived from a biological source. In other instances, a lipid material is derived from a synthetic source. In some instances, a lipid comprises one or more aliphatic alcohols and / or acids linked by glycerol and / or glycol moieties. In other instances, a lipid comprises aliphatic chains, linear conjugated, aromatic, and / or cyclic aliphatic moieties. In some embodiments, a lipid refers to a pure chemical entity. In other embodiments, a lipid refers to a mixture of several pure chemical entities. For example, lipids include, but are not limited to: paraffin wax, montan wax, microcrystalline wax, polyethylene wax, petrolatum wax, ozokerite wax, ceresin wax, beeswax, lanolin wax, spermaceti wax, tallow wax, lac wax, Chinese insect wax, ambergris wax, soy wax, carnauba wax, candelilla wax, coconut wax, palm kernel wax, rice bran wax, butyric acid, / / - butanol, pentanoic acid, / / -pentanol, hexanoic acid, w-hexanol, heptanoic acid, / / -heptanol, caprylic acid, n-octanol, nonanoic acid, / / -nonanol, capric acid, n-decanol, lauric acid, n- dodecanol, myristic acid, / / -tetradecanol, palmitic acid, n-hexadecanol, stearic acid, n- octadecanol, arachidonic acid, / / -icosanol, fatty alcohol monoglyceride ethers, fatty acid monoglyceride esters, fatty alcohol diglyceride ethers, fatty acid diglyceride esters, fatty alcohol triglyceride ethers, fatty acid triglyceride esters, fatty alcohol glycol monoether, fatty acid glycol monoesters, fatty alcohol glycol diethers, fatty acid glycol diesters, fatty alcohol poly(glycerol) ethers, fatty acid poly(glycerol) esters, fatty alcohol poly(glycol) ethers, fatty acid poly(glycol) esters, coconut oil, corn oil, cottonseed oil, olive oil, palm oil, peanut oil, rapeseed oil, safflower oil, sesame oil, soybean oil, sunflower oil, almond oil, pine nut oil, cashew oil, fully hydrogenated palm oil, partially hydrogenated palm oil, fully hydrogenated sunflower oil, partially hydrogenated sunflower oil, fully hydrogenated soybean oil, partially hydrogenated soybean oil, fully hydrogenated vegetable oil, partially hydrogenated vegetable oil, fully hydrogenated cottonseed oil, partially hydrogenated cottonseed oil, cholesterol, cholenic acid, ursolic acid, or betulinic acid.

[0117] Lyophilized: As used herein, the term “lyophilized” is used to refer to the endproduct of a process by which water is removed from a material via sublimation. In someinstances, prior to sublimation of water, the material is cooled to < -10 °C, < -20 °C, < -30 °C, < - 40°C, < -50°C, < -60°C, and / or < -70 °C. In some instances, prior to the sublimation of water, the pressure is lowered to < 200 torr, < 150 torr, < 100 torr, < 50 torr, < 10 torr, < 5 torr, and / or < 1 torr. Those skilled in the art recognize that the cooling temperature and pressure influence the physicochemical properties of the end product; it is understood that “lyophilized” encompasses all suitable manners of cooling and vacuum protocol.

[0118] Particle: As used herein, the term “particle” is used to refer to a discrete physical entity, typically having a size (e.g., a longest cross-section, such as a diameter) within a range. For example, a particle can have a size of 5 nm to 150 nm, about 10 nm to 150 nm, about 15 nm to 150 nm, about 20 nm to 150 nm, about 25 nm to 150 nm, about 30 nm to 150 nm, about 35 nm to 150 nm, about 40 nm to 150 nm, about 45 nm to 150 nm, about 50 nm to 150 nm, about 55 nm to 150 nm, about 60 nm to 150 nm, about 65 nm to 150 nm, about 70 nm to 150 nm, about 75 nm to 150 nm, about 80 nm to 150 nm, about 85 nm to 150 nm, about 90 nm to 150 nm, about 95 nm to 150 nm, about 100 nm to 150 nm, about 105 nm to 150 nm, about 110 nm to 150 nm, about 115 nm to 150 nm, about 120 nm to 150 nm, about 125 nm to 150 nm, about 130 nm to 150 nm, about 135 nm to 150 nm, about 140 nm to 150 nm, about 145 nm to 150 nm, about 5 nm to 125 nm, about 10 nm to 125 nm, about 15 nm to 125 nm, about 20 nm to 125 nm, about 25 nm to 125 nm, about 30 nm to 125 nm, about 35 nm to 125 nm, about 40 nm to 125 nm, about 45 nm to 125 nm, about 50 nm to 125 nm, about 55 nm to 125 nm, about 60 nm to 125 nm, about 65 nm to 125 nm, about 70 nm to 125 nm, about 75 nm to 125 nm, about 80 nm to 125 nm, about 85 nm to 125 nm, about 90 nm to 125 nm, about 95 nm to 125 nm, about 100 nm to 125 nm, about 105 nm to125 nm, about 110 nm to 125 nm, about 115 nm to 125 nm, about 120 nm to 125 nm, about 5 nm to 100 nm, about 10 nm to 100 nm, about 15 nm to 100 nm, about 20 nm to 100 nm, about 25 nm to 100 nm, about 30 nm to 100 nm, about 35 nm to 100 nm, about 40 nm to 100 nm, about 45 nm to 100 nm, about 50 nm to 100 nm, about 55 nm to 100 nm, about 60 nm to 100 nm, about 65 nm to 100 nm, about 70 nm to 100 nm, about 75 nm to 100 nm, about 80 nm to 100 nm, about 85 nm to 100 nm, about 90 nm to 100 nm, about 95 nm to 100 nm, about 5 nm to 75 nm, about 10 nm to75 nm, about 15 nm to 75 nm, about 20 nm to 75 nm, about 25 nm to 75 nm, about 30 nm to 75 nm, about 35 nm to 75 nm, about 40 nm to 75 nm, about 45 nm to 75 nm, about 50 nm to 75 nm, about 55 nm to 75 nm, about 60 nm to 75 nm, about 65 nm to 75 nm, about 5 nm to 50 nm, about 10 nm to 50 nm, about 15 nm to 50 nm, about 20 nm to 50 nm, about 25 nm to 50 nm, about 30nm to 50 nm, about 35 nm to 50 nm, about 40 nm to 50 nm, about 45 nm to 50 nm, about 5 nm to 25 nm, about 10 nm to 25 nm, about 15 nm to 25 nm, or about 20 nm to 25 nm. A “particle” is not limited to a particular shape or form, for example, having a cross-section shape of a sphere, an oval, a triangle, a square, a hexagon, or an irregular shape. In some embodiments, particles can be solid particles. In some embodiments, particles can be liquid particles. In some embodiments, particles can be gel or gel-like particles. In some embodiments, particles may have a particle-in-particle structure wherein a layer of one material (e.g., one type of polymer component) encapsulates another material (e.g., another type of polymer component, which may itself encapsulate yet another, or rather may be or comprise a “core” - e.g., a polymer matrix core - of the particle). In some embodiments, a “particle” can include, but is not limited to a liposome or liposomal particle having a lipid membrane (e.g., a lipid bilayer) encapsulating an aqueous / hydrophilic core.

[0119] Parts per million (ppm): As used herein, 1 ppm (“parts per million”) is equivalent to 1 milligram per liter (mg / L) or 1 milligram per kilogram (mg / kg).

[0120] pH Responsive: The term “pH-responsive” is used to refer to certain polymer component(s) as described herein, and in particular means that the relevant polymer component is characterized in that one or more aspects of its structure or arrangement is altered when exposed to a change in pH condition (e.g., to a particular pH and / or to a pH change of particular magnitude). In some embodiments, a polymer component is considered to be “pH-responsive” if, when the relevant polymer component is associated with a payload component in a particle preparation as described herein, the particle preparation releases the payload component under specific pH condition(s). In some embodiments, >90% of payload component is released from a particle preparation that includes a pH-responsive polymer component within 15 minutes when the particle preparation is exposed to a particular defined pH condition (e.g., within a range of defined pH values and / or at a specific pH value); in some embodiments, such release results when such contacting occurs at temperatures between 33-40 °C, and in aqueous-based buffers of ionic strength ranging from 0.001-0.151 M (e.g., water, simulated gastric fluid, gastric fluid, simulated intestinal fluid, intestinal fluid) with osmolality between 1-615 mOsm / kg. In some embodiments, a pH-responsive polymer component is one that degrades when exposed to a particular pH or pH change. Alternatively or additionally, in some embodiments, a pH-responsive polymer component is one that becomes soluble, or significantly (e.g., by at least about 5%) increases its solubility when exposed to a particular pH level, or pH change. In some embodiments, a pH-responsive polymer component includes one or more moieties whose protonation state changes at the relevant pH or in response to the relevant pH change. For example, in some embodiments, a pH responsive polymer component includes one or more amine moieties that become protonated upon exposure to a relevant pH or pH chance.

[0121] Reference: As used herein describes a standard or control relative to which a comparison is made. For example, in some embodiments, an agent, animal, individual, population, sample, sequence or value of interest is compared with a reference or control agent, animal, individual, population, sample, sequence or value. In some embodiments, a reference or control is tested and / or determined substantially simultaneously with the testing or determination of interest. In some embodiments, a reference or control is a historical reference or control, optionally embodied in a tangible medium. Typically, as would be understood by those skilled in the art, a reference or control is determined or characterized under comparable conditions or circumstances to those under assessment. Those skilled in the art will appreciate when sufficient similarities are present to justify reliance on and / or comparison to a particular possible reference or control.

[0122] Residual solvent: As used herein, the term “residual solvent” refers to a solvent that remains in a material after manufacture or processing of the material. In some embodiments, level of residual solvent is assessed by high performance liquid chromatography HPLC, mass spec, nuclear magnetic resonance (NMR) spectrometry, Fourier transform infrared (FTIR) spectroscopy, and / or gas chromatography.

[0123] Stable: The term “stable,” when applied to compositions herein, means that the compositions maintain (e.g., as determined by one or more analytical assessments) one or more aspects of their physical structure and / or performance characteristic(s) (e.g., activity) over a period of time and / or under a designated set of conditions. When an assessed composition is a particle composition, in some embodiments, as will be clear from context to those skilled in the art, the term “stable” refers to maintenance of a characteristic such as average particle size, maximum and / or minimum particle size, range of particle sizes, and / or distribution of particlesizes (i.e., the percentage of particles above a designated size and / or outside a designated range of sizes) over a period of time and / or under a designated set of conditions.

[0124] Temperature-responsive: As used herein, the term “temperature-responsive” is used to refer to certain polymer component(s) as described herein, and in particular means that the relevant polymer component is characterized in that one or more aspects of its structure or arrangement is altered when exposed to a change in temperature condition (e.g., to a particular temperature and / or to a temperature change of particular magnitude). In some embodiments, a polymer component is considered to be “temperature-responsive” if, when the relevant polymer component is associated with a payload component in a particle preparation as described herein, amorphous regions of the polymer component experience a transition from a rigid state (e.g., glassy state) to a more fluid-like flexible state (e.g., more conducive to flow), at a temperature close to the point of transition from the solid state to rubbery state (e.g., glass transition).

[0125] Water activity: As used herein, “water activity” of a material is an indication (e.g., a measurement) of how much free (i.e., available to bind or react) water is present in the material and is typically determined as the ratio of the vapor pressure of water in a material (p) to the vapor pressure of pure water (po) at the same temperature. For example, a water activity of 0.80 means the vapor pressure is 80 percent of that of pure water. Water activity typically increases with temperature. Those skilled in the art will be familiar with three basic water activity measurement systems: Preventive Electrolytic Hygrometers (REH), Capacitance Hygrometers, and Dew Point Hygrometers (sometimes called chilled mirror).DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

[0126] It is contemplated that systems, devices, methods, and processes of the disclosure encompass variations and adaptations developed using information from the embodiments described herein. Adaptation and / or modification of the systems, devices, methods, and processes described herein may be performed by those of ordinary skill in the relevant art.

[0127] Throughout the description, where articles, devices, and systems are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are articles, devices, and systems according to certain embodiments of the present disclosure that consist essentially of, or consist of, the recited components, and that there are processes and methods according to certain embodiments of the present disclosure that consist essentially of, or consist of, the recited processing steps.

[0128] It should be understood that the order of steps or order for performing certain action is immaterial so long as operability is not lost. Moreover, two or more steps or actions may be conducted simultaneously. As is understood by those skilled in the art, the terms “over”, “under”, “above”, “below”, “beneath”, and “on” are relative terms and can be interchanged in reference to different orientations of the layers, elements, and substrates included in the present disclosure. For example, a first layer on a second layer, in some embodiments means a first layer directly on and in contact with a second layer. In other embodiments, a first layer on a second layer can include another layer there between.

[0129] Headers are provided for the convenience of the reader and are not intended to be limiting with respect to the claimed subject matter.Microemulsion Particle FormulationsCompositions

[0130] The present disclosure provides formulations including one or more microemulsion particles and at least 80% w / v water, wherein the one or more microemulsion particles incorporate a payload component, a fatty acid component, a surfactant component, an antioxidant component, and a stabilizing component.

[0131] In some embodiments, a payload component incorporated in a microemulsion particle of the present disclosure includes a hydrophobic payload, a hydrophilic payload, or both a hydrophobic and hydrophilic payload. In some embodiments, a payload component incorporated in a microemulsion particle of the present disclosure includes, but is not limited to, an antioxidant, a vitamin, a stimulant, an energy source or supplement, a polyphenol, a carotenoid, an herbal supplement, and a flavonoid. For example, in some embodiments, apayload component includes lutein, vitamin D, zeaxanthin, vitamin A, caffeine, vitamin Bl 2, creatine, creatine ethyl ester, creatine phosphate, tannic acid, theaflavin, theaflavin gallate, thearubigins, ellagitannins, catechins, epigallocatechin gallate, gallic acid and its alkyl esters, glucose, curcurmin, quercetin, rutin, naringenin, fatty acids, a nutritive and / or bioactive peptide, a feruloylated arabinoxylan-enriched fiber, heat-treated whey protein isolate, sodium caseinate, collagen, gelatin, rice bran, wheat bran, resistant corn dextrin, resistant potato dextrin or a combination thereof. In some embodiments, the payload component provides a nutritional, health, and / or stimulatory benefit to a subject when the formulation is consumed by the subject.

[0132] In some embodiments, a payload component includes a single payload or a combination of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, or 20 or more payloads. In some embodiments having two or more payloads, a molar ratio between at least two payloads is about 1 to 30. For example, in some embodiments, a molar ratio between at least two payloads is about 1 to 30, about 5 to 30, about 10 to 30, about 15 to 30, about 20 to 30, about 25 to 30, about 1 to 25, about 5 to 25, about 10 to 25, about 15 to 25, about 20 to 25, about 1 to 20, about 5 to 20, about 10 to 20, about 15 to 20, about 1 to 15, about 5 to 15, about 10 to 15, about 1 to 10, about 5 to 10, or about 1 to 5. In some embodiments, a molar ratio between at least two payloads is about 1, about 2, about 3, about 4, about 5, about 6, about 10, about 15, about 20, or about 25.

[0133] In some embodiments, a microemulsion particle of the present disclosure includes about 0.01 wt% to 0.15 wt% of a payload component. For example, in some embodiments, a microemulsion particle of the present disclosure includes about 0.01 wt% to 0.15 wt%, about 0.03 wt% to 0.15 wt%, about 0.05 wt% to 0.15 wt%, about 0.07 wt% to 0.15 wt%, about 0.09 wt% to 0.15 wt%, about 0.11 wt% to 0.15 wt%, about 0.13 wt% to 0.15 wt%, about 0.01 wt% to 0.13 wt%, about 0.03 wt% to 0.13 wt%, about 0.05 wt% to 0.13 wt%, about 0.07 wt% to 0.13 wt%, about 0.09 wt% to 0.13 wt%, about 0.11 wt% to 0.13 wt%, about 0.01 wt% to 0.11 wt%, about 0.03 wt% to 0.11 wt%, about 0.05 wt% to 0.11 wt%, about 0.07 wt% to 0.11 wt%, about 0.09 wt% to 0.11 wt%, about 0.01 wt% to 0.09 wt%, about 0.03 wt% to 0.09 wt%, about 0.05 wt% to 0.09 wt%, about 0.07 wt% to 0.09 wt%, about 0.01 wt% to 0.07 wt%, about 0.03 wt% to 0.07 wt%, about 0.05 wt% to 0.07 wt%, about 0.01 wt% to 0.05 wt%, about 0.03 wt% to 0.05 wt%, or about 0.01 wt% to 0.03 wt% of a payload component. In some embodiments, amicroemulsion particle of the present disclosure includes about 0.01 wt% to 0.13 wt% of a payload component.

[0134] In some embodiments, such a microemulsion particle includes a complexing agent. In some embodiments, a complexing agent interacts with a payload component. In some embodiments, a microemulsion particle includes a molar ratio of payload component to complexing agent greater than about 3: 1, greater than about 3.5: 1, greater than about 4: 1, greater than about 4.5: 1, greater than about 5: 1, greater than about 5.5: 1, or greater than about 6: 1. In some embodiments, a payload component is caffeine, and a complexing agent includes, but is not limited to, tannic acid, a catechin, epigallocatechin-3 -gallate, gallic acid or a derivative thereof, or an alagitannin. In some embodiments, a complexing agent includes, but is not limited to, tannic acid, a catechin, epigallocatechin-3 -gallate, gallic acid or a derivative thereof, or an alagitannin. In some embodiments, a payload component is caffeine and a complexing agent is tannic acid.

[0135] In some embodiments, a microemulsion particle of the present disclosure includes a fatty component selected from, but not limited to, soybean oil, corn oil, safflower oil, olive oil, stearine, beeswax, canola oil, mineral oil, sunflower oil, glyceryl tripalmitate, medium chain triglycerides, coconut oil, or combination thereof.

[0136] In some embodiments, a microemulsion particle of the present disclosure includes about 0.1 wt% to 2 wt% of a fatty component. For example, in some embodiments, a microemulsion particle of the present disclosure includes about 0.1 wt% to 2 wt%, about 0.2 wt% to 2 wt%, about 0.3 wt% to 2 wt%, about 0.4 wt% to 2 wt%, about 0.5 wt% to 2 wt%, about 0.6 wt% to 2 wt%, about 0.7 wt% to 2 wt%, about 0.8 wt% to 2 wt%, about 0.9 wt% to 2 wt%, about 1 wt% to 2 wt%, about 1.1 wt% to 2 wt%, about 1.2 wt% to 2 wt%, about 1.3 wt% to 2 wt%, about 1.4 wt% to 2 wt%, about 1.5 wt% to 2 wt%, about 1.6 wt% to 2 wt%, about 1.7 wt% to 2 wt%, about 1.8 wt% to 2 wt%, about 1.9 wt% to 2 wt%, about 0.1 wt% to 1.8 wt%, about 0.2 wt% to 1.8 wt%, about 0.3 wt% to 1.8 wt%, about 0.4 wt% to 1.8 wt%, about 0.5 wt% to 1.8 wt%, about 0.6 wt% to 1.8 wt%, about 0.7 wt% to 1.8 wt%, about 0.8 wt% to 1.8 wt%, about 0.9 wt% to 1.8 wt%, about 1 wt% to 1.8 wt%, about 1.1 wt% to 1.8 wt%, about 1.2 wt% to 1.8 wt%, about 1.3 wt% to 1.8 wt%, about 1.4 wt% to 1.8 wt%, about 1.5 wt% to 1.8 wt%, about 1.6 wt% to 1.8 wt%, about 1.7 wt% to 1.8 wt%, about 0.1 wt% to 1.6 wt%, about 0.2 wt% to 1.6 wt%,about 0.3 wt% to 1 .6 wt%, about 0.4 wt% to 1 .6 wt%, about 0.5 wt% to 1 .6 wt%, about 0.6 wt% to 1.6 wt%, about 0.7 wt% to 1.6 wt%, about 0.8 wt% to 1.6 wt%, about 0.9 wt% to 1.6 wt%, about 1 wt% to 1.6 wt%, about 1.1 wt% to 1.6 wt%, about 1.2 wt% to 1.6 wt%, about 1.3 wt% to 1.6 wt%, about 1.4 wt% to 1.6 wt%, about 1.5 wt% to 1.6 wt%, about 0.1 wt% to 1.4 wt%, about 0.2 wt% to 1.4 wt%, about 0.3 wt% to 1.4 wt%, about 0.4 wt% to 1.4 wt%, about 0.5 wt% to 1.4 wt%, about 0.6 wt% to 1.4 wt%, about 0.7 wt% to 1.4 wt%, about 0.8 wt% to 1.4 wt%, about 0.9 wt% to 1.4 wt%, about 1 wt% to 1.4 wt%, about 1.1 wt% to 1.4 wt%, about 1.2 wt% to 1.4 wt%, about 1.3 wt% to 1.4 wt%, about 0.1 wt% to 1.2 wt%, about 0.2 wt% to 1.2 wt%, about 0.3 wt% to 1.2 wt%, about 0.4 wt% to 1.2 wt%, about 0.5 wt% to 1.2 wt%, about 0.6 wt% to 1.2 wt%, about 0.7 wt% to 1.2 wt%, about 0.8 wt% to 1.2 wt%, about 0.9 wt% to 1.2 wt%, about 1 wt% to 1.2 wt%, about 1.1 wt% to 1.2 wt%, about 0.1 wt% to 1 wt%, about 0.2 wt% to 1 wt%, about 0.3 wt% to 1 wt%, about 0.4 wt% to 1 wt%, about 0.5 wt% to 1 wt%, about 0.6 wt% to 1 wt%, about 0.7 wt% to 1 wt%, about 0.8 wt% to 1 wt%, about 0.9 wt% to 1 wt%, about 0.1 wt% to 0.8 wt%, about 0.2 wt% to 0.8 wt%, about 0.3 wt% to 0.8 wt%, about 0.4 wt% to 0.8 wt%, about 0.5 wt% to 0.8 wt%, about 0.6 wt% to 0.8 wt%, about 0.7 wt% to 0.8 wt%, about 0.1 wt% to 0.6 wt%, about 0.2 wt% to 0.6 wt%, about 0.3 wt% to 0.6 wt%, about 0.4 wt% to 0.6 wt%, about 0.5 wt% to 0.6 wt%, about 0.1 wt% to 0.4 wt%, about 0.2 wt% to 0.4 wt%, about 0.3 wt% to 0.4 wt%, or about 0.1 wt% to 0.2 wt% of a fatty component.

[0137] In some embodiments, a microemulsion particle of the present disclosure includes a surfactant component selected from, but not limited to, polysorbate 80, polysorbate 60, saponin, coco glucoside, 12-hydroxystearic acid, palmitic acid, stearic acid, polyvinylpyrrolidone, propylene glycol, polygly ceryl- 10 dicaprate / dicaprylate, polyglyceryl- 10 laurate, polyglyceryl- 10 caprate / caprylate, sucrose monolaurate, sucrose monopalmitate, sucrose monostearate, oat polar lipid fraction, or a combination thereof.

[0138] In some embodiments, a microemulsion particle of the present disclosure includes about 14 wt% to 20 wt% of a surfactant component. For example, in some embodiments a microemulsion particle of the present disclosure includes about 14 wt% to 20 wt%, about15 wt% to 20 wt%, about 16 wt% to 20 wt%, about 17 wt% to 20 wt%, about 18 wt% to 20 wt%, about 19 wt% to 20 wt%, about 14 wt% to 19 wt%, about 15 wt% to 19 wt%, about 16 wt% to 19 wt%, about 17 wt% to 19 wt%, about 18 wt% to 19 wt%, about 14 wt% to 18 wt%, about15 wt% to 18 wt%, about 16 wt% to 18 wt%, about 17 wt% to 18 wt%, about 14 wt% to 17 wt%, about 15 wt% to 17 wt%, about 16 wt% to 17 wt%, about 14 wt% to 16 wt%, about 15wt% to 16 wt%, or about 14 wt% to 15 wt% of a surfactant component.

[0139] In some embodiments, a microemulsion particle of the present disclosure includes an antioxidant component. In some embodiments, an antioxidant component prevents the oxidation of the microemulsion particle. In some embodiments, an antioxidant component prevents the oxidation of a payload component. In some embodiments, a microemulsion particle of the present disclosure includes an antioxidant component selected from, but not limited to, a- tocopherol, rosemary oil, citric acid, glutathione, astaxanthin, butylated hydroxyanisole, butylated hydroxytoluene, gum guaiac, or combination thereof.

[0140] In some embodiments, a microemulsion particle of the present disclosure includes about 0.1 wt% to 10.0 wt% of an antioxidant component. For example, in some embodiments, a microemulsion particle of the present disclosure includes about 0.1 wt% to 2.0 wt%, about 0.2 wt% to 2.0 wt%, about 0.4 wt% to 2.0 wt%, about 0.6 wt% to 2.0 wt%, about 0.8 wt% to 2.0 wt%, about 1.0 wt% to 2.0 wt%, about 1.2 wt% to 2.0 wt%, about 1.4 wt% to 2.0 wt%, about 1.6 wt% to 2.0 wt%, about 1.8 wt% to 2.0 wt%, about 0.1 wt% to 1.8 wt%, about 0.2 wt% to 1.8 wt%, about 0.4 wt% to 1.8 wt%, about 0.6 wt% to 1.8 wt%, about 0.8 wt% to 1.8 wt%, about 1.0 wt% to 1.8 wt%, about 1.2 wt% to 1.8 wt%, about 1.4 wt% to 1.8 wt%, about 1.6 wt% to 1.8 wt%, about 0.1 wt% to 1 .6 wt%, about 0.2 wt% to 1 .6 wt%, about 0.4 wt% to 1 .6 wt%, about 0.6 wt% to 1.6 wt%, about 0.8 wt% to 1.6 wt%, about 1.0 wt% to 1.6 wt%, about 1.2 wt% to 1.6 wt%, about 1.4 wt% to 1.6 wt%, about 0.1 wt% to 1.4 wt%, about 0.2 wt% to 1.4 wt%, about 0.4 wt% to 1.4 wt%, about 0.6 wt% to 1.4 wt%, about 0.8 wt% to 1.4 wt%, about 1.0 wt% to 1.4 wt%, about 1.2 wt% to 1.4 wt%, about 0.1 wt% to 1.2 wt%, about 0.2 wt% to 1.2 wt%, about 0.4 wt% to 1.2 wt%, about 0.6 wt% to 1.2 wt%, about 0.8 wt% to 1.2 wt%, about 1.0 wt% to 1.2 wt%, about 0.1 wt% to 1.0 wt%, about 0.2 wt% to 1.0 wt%, about 0.4 wt% to 1.0 wt%, about 0.6 wt% to 1.0 wt%, about 0.8 wt% to 1.0 wt%, about 0.1 wt% to 0.8 wt%, about 0.2 wt% to 0.8 wt%, about 0.4 wt% to 0.8 wt%, about 0.6 wt% to 0.8 wt%, about 0.1 wt% to 0.6 wt%, about 0.2 wt% to 0.6 wt%, about 0.4 wt% to 0.6 wt%, about 0.1 wt% to 0.4 wt%, about 0.2 wt% to 0.4 wt%, or 0.1 wt% to 0.2 wt% of an antioxidant component. In some embodiments, amicroemulsion particle of the present disclosure includes about 0.1 wt% to 2 wt% of an antioxidant component.

[0141] In some embodiments, a microemulsion particle of the present disclosure includes a stabilizing component. In some embodiments, a stabilizing component preserves the structural integrity of a payload component and / or prevents degradation of the payload component. In some embodiments, a stabilizing component promotes encapsulation of a payload component in the microemulsion particle. In some embodiments, a stabilizing component preserves the structural integrity of the microemulsion particle. In some embodiments, a stabilizing agent prevent particles from aggregating, diffusing and degrading. In some embodiments, a microemulsion particle of the present disclosure includes a stabilizing component selected from, but not limited to, buttermilk, stearyl alcohol, glycerol, citric acid, lecithin, choline bicarbonate, xanthan gum, tara gum, konjac gum, tragacanth gum, guar gum, cationic guar gum, chitosan, spermidine-rich wheat germ extract, cetyltrimethylammonium bromide, sodium dioctylsulfosuccinate, sodium lauryl sulfate, starch phosphates, tartaric acid esters of mono- and di-glycerides, metatartaric acid, whey protein isolate, casein, gum arabic, sodium alginates, maltose, pectins, carrageenans, iron(III) sulfate, iron(III) hydroxide, P-sitosterol, cholesterol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, tetradecanol, octadecanol, hexadecanol, carboxymethyl cellulose, sterol, stanol, cardiolipin, or combination thereof.

[0142] In some embodiments, a microemulsion particle of the present disclosure includes about 0.1 wt% to 5.0 wt% of a stabilizing component. For example, in some embodiments, a microemulsion particle of the present disclosure includes about 0.1 wt% to 5.0 wt%, about 0.2 wt% to 5.0 wt%, about 0.4 wt% to 5.0 wt%, about 0.6 wt% to 5.0 wt%, about 0.8 wt% to 5.0 wt%, about 1.0 wt% to 5.0 wt%, about 1.2 wt% to 5.0 wt%, about 1.4 wt% to 5.0 wt%, about 1.6 wt% to 5.0 wt%, about 1.8 wt% to 5.0 wt%, about 2.0 wt% to 5.0 wt%, about 2.2 wt% to 5.0 wt%, about 2.4 wt% to 5.0 wt%, about 2.6 wt% to 5.0 wt%, about 2.8 wt% to 5.0 wt%, about 3.0 wt% to 5.0 wt%, about 3.2 wt% to 5.0 wt%, about 3.4 wt% to 5.0 wt%, about 3.6 wt% to 5.0 wt%, about 3.8 wt% to 5.0 wt%, about 4.0 wt% to 5.0 wt%, about 4.2 wt% to 5.0 wt%, about 4.4 wt% to 5.0 wt%, about 4.6 wt% to 5.0 wt%, about 4.8 wt% to 5.0 wt%, about 0.1 wt% to 4.5 wt%, about 0.2 wt% to 4.5 wt%, about 0.4 wt% to 4.5 wt%, about 0.6 wt% to 4.5 wt%, about 0.8wt% to 4.5 wt%, about 1 .0 wt% to 4.5 wt%, about 1 .2 wt% to 4.5 wt%, about 1 .4 wt% to 4.5 wt%, about 1.6 wt% to 4.5 wt%, about 1.8 wt% to 4.5 wt%, about 2.0 wt% to 4.5 wt%, about 2.2 wt% to 4.5 wt%, about 2.4 wt% to 4.5 wt%, about 2.6 wt% to 4.5 wt%, about 2.8 wt% to 4.5 wt%, about 3.0 wt% to 4.5 wt%, about 3.2 wt% to 4.5 wt%, about 3.4 wt% to 4.5 wt%, about 3.6 wt% to 4.5 wt%, about 3.8 wt% to 4.5 wt%, about 4.0 wt% to 4.5 wt%, about 4.2 wt% to 4.5 wt%, about 4.4 wt% to 4.5 wt%, about 0.1 wt% to 4.0 wt%, about 0.2 wt% to 4.0 wt%, about 0.4 wt% to 4.0 wt%, about 0.6 wt% to 4.0 wt%, about 0.8 wt% to 4.0 wt%, about 1.0 wt% to 4.0 wt%, about 1.2 wt% to 4.0 wt%, about 1.4 wt% to 4.0 wt%, about 1.6 wt% to 4.0 wt%, about 1.8 wt% to 4.0 wt%, about 2.0 wt% to 4.0 wt%, about 2.2 wt% to 4.0 wt%, about 2.4 wt% to 4.0 wt%, about 2.6 wt% to 4.0 wt%, about 2.8 wt% to 4.0 wt%, about 3.0 wt% to 4.0 wt%, about 3.2 wt% to 4.0 wt%, about 3.4 wt% to 4.0 wt%, about 3.6 wt% to 4.0 wt%, about 3.8 wt% to 4.0 wt%, about 0.1 wt% to 3.5 wt%, about 0.2 wt% to 3.5 wt%, about 0.4 wt% to 3.5 wt%, about 0.6 wt% to 3.5 wt%, about 0.8 wt% to 3.5 wt%, about 1.0 wt% to 3.5 wt%, about 1.2 wt% to 3.5 wt%, about 1.4 wt% to 3.5 wt%, about 1.6 wt% to 3.5 wt%, about 1.8 wt% to 3.5 wt%, about 2.0 wt% to 3.5 wt%, about 2.2 wt% to 3.5 wt%, about 2.4 wt% to 3.5 wt%, about 2.6 wt% to 3.5 wt%, about 2.8 wt% to 3.5 wt%, about 3.0 wt% to 3.5 wt%, about 3.2 wt% to 3.5 wt%, about 3.4 wt% to 3.5 wt%, about 0.1 wt% to 3.0 wt%, about 0.2 wt% to 3.0 wt%, about 0.4 wt% to 3.0 wt%, about 0.6 wt% to 3.0 wt%, about 0.8 wt% to 3.0 wt%, about 1.0 wt% to 3.0 wt%, about 1.2 wt% to 3.0 wt%, about 1.4 wt% to 3.0 wt%, about 1.6 wt% to 3.0 wt%, about 1.8 wt% to 3.0 wt%, about 2.0 wt% to 3.0 wt%, about 2.2 wt% to 3.0 wt%, about 2.4 wt% to 3.0 wt%, about 2.6 wt% to 3.0 wt%, about 2.8 wt% to 3.0 wt%, about 0.1 wt% to 2.5 wt%, about 0.2 wt% to 2.5 wt%, about 0.4 wt% to 2.5 wt%, about 0.6 wt% to 2.5 wt%, about 0.8 wt% to 2.5 wt%, about 1.0 wt% to 2.5 wt%, about 1.2 wt% to 2.5 wt%, about 1.4 wt% to 2.5 wt%, about 1.6 wt% to 2.5 wt%, about 1.8 wt% to 2.5 wt%, about 2.0 wt% to 2.5 wt%, about 2.2 wt% to 2.5 wt%, about 2.4 wt% to 2.5 wt, about 0. 1 wt% to 2.0 wt%, about 0.2 wt% to 2.0 wt%, about 0.4 wt% to 2.0 wt%, about 0.6 wt% to 2.0 wt%, about 0.8 wt% to 2.0 wt%, about 1.0 wt% to 2.0 wt%, about 1.2 wt% to 2.0 wt%, about 1.4 wt% to 2.0 wt%, about 1.6 wt% to 2.0 wt%, about 1.8 wt% to 2.0 wt%, about 0.1 wt% to 1.5 wt%, about 0.2 wt% to 1.5 wt%, about 0.4 wt% to 1.5 wt%, about 0.6 wt% to 1.5 wt%, about 0.8 wt% to 1.5 wt%, about 1.0 wt% to 1.5 wt%, about 1.2 wt% to 1.5 wt%, about 1.4 wt% to 1.5 wt%, about 0.1 wt% to 1.0 wt%, about 0.2 wt% to 1.0 wt%, about 0.4 wt% to 1.0 wt%, about 0.6 wt% to 1.0 wt%, about 0.8 wt% to 1.0 wt%, about 0.1 wt% to 0.5 wt%,about 0.2 wt% to 0.5 wt%, or about 0.4 wt% to 0.5 wt% of a stabilizing component. In some embodiments, a microemulsion particle of the present disclosure includes about 0.1 wt % to 4 wt% of a stabilizing component.

[0143] In some embodiments, microemulsion particles of the present disclosure may have a distribution of diameters (e.g., Dv(10), Dv(20), Dv(30), Dv(40), Dv(50), Dv(60), Dv(70), Dv(80), Dv(90), Dv(99), etc.). In some embodiments, microemulsion particles of the present disclosure may have a distribution of diameters (e.g., Dv(10), Dv(20), Dv(30), Dv(40), Dv(50), Dv(60), Dv(70), Dv(80), Dv(90), Dv(99), etc.) of up to about 3000 pm, up to about 2000 pm, up to about 1000 pm, up to about 500 pm, up to about 400 pm, up to about 300 pm, up to about 200 pm, up to about 100 pm, up to about 50 pm, up to about 40 pm, up to about 30 pm, up to about 20 pm, up to about 10 pm, or up to about 5 pm.

[0144] In some embodiments, a microemulsion particle of the present disclosure has a diameter, or particles of a provided microemulsion formulation have an average diameter, within a range from about 5 nm to 150 nm, about 10 nm to 150 nm, about 15 nm to 150 nm, about 20 nm to 150 nm, about 25 nm to 150 nm, about 30 nm to 150 nm, about 35 nm to 150 nm, about 40 nm to 150 nm, about 45 nm to 150 nm, about 50 nm to 150 nm, about 55 nm to 150 nm, about 60 nm to 150 nm, about 65 nm to 150 nm, about 70 nm to 150 nm, about 75 nm to 150 nm, about 80 nm to 150 nm, about 85 nm to 150 nm, about 90 nm to 150 nm, about 95 nm to 150 nm, about100 nm to 150 nm, about 105 nm to 150 nm, about 1 10 nm to 150 nm, about 1 15 nm to 150 nm, about 120 nm to 150 nm, about 125 nm to 150 nm, about 130 nm to 150 nm, about 135 nm to150 nm, about 140 nm to 150 nm, about 145 nm to 150 nm, about 5 nm to 125 nm, about 10 nm to 125 nm, about 15 nm to 125 nm, about 20 nm to 125 nm, about 25 nm to 125 nm, about 30 nm to 125 nm, about 35 nm to 125 nm, about 40 nm to 125 nm, about 45 nm to 125 nm, about 50 nm to 125 nm, about 55 nm to 125 nm, about 60 nm to 125 nm, about 65 nm to 125 nm, about 70 nm to 125 nm, about 75 nm to 125 nm, about 80 nm to 125 nm, about 85 nm to 125 nm, about 90 nm to 125 nm, about 95 nm to 125 nm, about 100 nm to 125 nm, about 105 nm to 125 nm, about 110 nm to 125 nm, about 115 nm to 125 nm, about 120 nm to 125 nm, about 5 nm to 100 nm, about10 nm to 100 nm, about 15 nm to 100 nm, about 20 nm to 100 nm, about 25 nm to 100 nm, about30 nm to 100 nm, about 35 nm to 100 nm, about 40 nm to 100 nm, about 45 nm to 100 nm, about50 nm to 100 nm, about 55 nm to 100 nm, about 60 nm to 100 nm, about 65 nm to 100 nm, about70 nm to 100 nm, about 75 nm to 100 nm, about 80 nm to 100 nm, about 85 nm to 100 nm, about 90 nm to 100 nm, about 95 nm to 100 nm, about 5 nm to 75 nm, about 10 nm to 75 nm, about 15 nm to 75 nm, about 20 nm to 75 nm, about 25 nm to 75 nm, about 30 nm to 75 nm, about 35 nm to 75 nm, about 40 nm to 75 nm, about 45 nm to 75 nm, about 50 nm to 75 nm, about 55 nm to 75 nm, about 60 nm to 75 nm, about 65 nm to 75 nm, about 5 nm to 50 nm, about 10 nm to 50 nm, about 15 nm to 50 nm, about 20 nm to 50 nm, about 25 nm to 50 nm, about 30 nm to 50 nm, about 35 nm to 50 nm, about 40 nm to 50 nm, about 45 nm to 50 nm, about 5 nm to 25 nm, about 10 nm to 25 nm, about 15 nm to 25 nm, or about 20 nm to 25 nm. For example, in some embodiments, microemulsion particles of the present disclosure have an average diameter of about 35 nm, about 36 nm, about 37 nm, about 38 nm, about 39 nm, about 40 nm, about 41 nm, about 42 nm, about 43 nm, about 44 nm, about 45 nm, about 46 nm, about 47 nm, about 48 nm, about 49 nm, about 50 nm, about 51 nm, about 52 nm, about 53 nm, about 54 nm, or about 55 nm.

[0145] In some embodiments, a microemulsion particle formulation provided and / or utilized in accordance with the present disclosure is characterized in that it has a crystalline solid form between about 15 °C to about 30 °C. In some embodiments, a microemulsion particle formulation described herein is a crystalline solid at about 20 °C. In some embodiments, a microemulsion particle formulation described herein maintains a crystalline solid form following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient- fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0146] In some embodiments, a microemulsion particle formulation provided and / or utilized in accordance with the present disclosure is characterized in that it has an amorphous solid form between about 15 °C to about 30 °C. In some embodiments, a microemulsion particle formulation is an amorphous solid at about 20 °C. In some embodiments, a microemulsionparticle formulation described herein maintains an amorphous solid form following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented nonalcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0147] In some embodiments, a microemulsion particle formulation provided and / or utilized in accordance with the present disclosure is characterized in that it has a gel form at least between about 15 °C to about 30 °C. In some embodiments, a microemulsion particle formulation described herein is a gel at about 20 °C. In some embodiments, a microemulsion particle formulation described herein maintains a gel form following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0148] In some embodiments, a microemulsion particle formulation provided and / or utilized in accordance with the present disclosure is characterized in that it has a paste form at least between about 15 °C to about 30 °C. In some embodiments, a microemulsion particle formulation described herein is a paste at about 20 °C. In some embodiments, a microemulsion particle formulation described herein maintains a paste form following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day,at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0149] In some embodiments, a microemulsion particle formulation provided and / or utilized in accordance with the present disclosure is characterized in that it is an ionic liquid at least between about 15 °C to about 30 °C. In some embodiments, a microemulsion particle described herein is an ionic liquid at about 20 °C. In some embodiments, a microemulsion particle described herein maintains an ionic liquid form following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0150] In some embodiments, a microemulsion particle formulation provided and / or utilized in accordance with the present disclosure is characterized in that it is a liquid at least between about 15°C to about 30°C. In some embodiments, a microemulsion particle described herein is a liquid at about 20°C. In some embodiments, a microemulsion particle described herein maintains a liquid form following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0151] In some embodiments, a microemulsion particle formulation described herein is characterized by a melting point within a range of about 25 °C to about 200 °C, about 50 °C to about 200 °C, about 75 °C to about 200 °C, about 100 °C to about 200 °C, about 125 °C to about 200 °C, about 150 °C to about 200 °C, about 175 °C to about 200 °C, about 25 °C to about 200 °C, about 50 °C to about 200 °C, about 75 °C to about 200 °C, about 100 °C to about 200 °C, about 125 °C to about 200 °C, about 150 °C to about 200 °C, about 175 °C to about 200 °C, about 25 °C to about 175 °C, about 50 °C to about 175 °C, about 75 °C to about 175 °C, about 100 °C to about 175 °C, about 125 °C to about 175 °C, about 150 °C to about 175 °C, about 175 °C to about 175 °C, about 25 °C to about 175 °C, about 50 °C to about 175 °C, about 75 °C to about 175 °C, about 100 °C to about 175 °C, about 125 °C to about 175 °C, about 150 °C to about 175 °C, about 25 °C to about 150 °C, about 50 °C to about 150 °C, about 75 °C to about 150 °C, about 100 °C to about 150 °C, about 125 °C to about 150 °C, about 150 °C to about 150 °C, about 175 °C to about 150 °C, about 25 °C to about 150 °C, about 50 °C to about 150 °C, about 75 °C to about 150 °C, about 100 °C to about 150 °C, about 125 °C to about 150 °C, about 25 °C to about 125 °C, about 50 °C to about 125 °C, about 75 °C to about 125 °C, about 100 °C to about 125 °C, about 125 °C to about 125 °C, about 150 °C to about 125 °C, about 175 °C to about 125 °C, about 25 °C to about 125 °C, about 50 °C to about 125 °C, about 75 °C to about 125 °C, about 100 °C to about 125 °C, about 25 °C to about 100 °C, about 50 °C to about 100 °C, about 75 °C to about 100 °C, about 25 °C to about 75 °C, about 50 °C to about 75 °C, or about 25 °C to about 50 °C.

[0152] In some embodiments a microemulsion particle formulation described herein is characterized by a viscosity within a range of about 0.01 Pa-s to about 100 Pa-s as measured by a rheometer. For example, in some embodiments a microemulsion particle formulation described herein is characterized by a viscosity within a range of about 0.01 Pa-s to about 100 Pa-s, about 0.1 Pa-s to about 100 Pa-s, 1 Pa-s to about 100 Pa-s, 10 Pa-s to about 100 Pa-s, 0.01 Pa-s to about 10 Pa-s, about 0.1 Pa-s to about 10 Pa-s, 1 Pa-s to about 10 Pa-s, 0.01 Pa-s to about 1 Pa-s, about 0.1 Pa-s to about 1 Pa-s, or about 0.01 Pa-s to about 0.1 Pa-s, as measured by a rheometer.

[0153] In some embodiments, a microemulsion particle formulation of the present disclosure is miscible in one or more aqueous solutions. In some embodiments, a microemulsion particle formulation described herein is miscible in coconut water, sparkling water, fermentednon-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, and / or baby formula.

[0154] In some embodiments, a microemulsion particle formulation of the present disclosure does not form aggregates, flocculates, bezoars, or sediments when combined with one or more aqueous solutions (for example, when combined with one or more beverages such as, for example, with one or more of coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula). In some embodiments, a microemulsion particle formulation of the present disclosure does not form aggregates, flocculates, bezoars, or sediments when added to one or more aqueous solutions (for example, with a beverage such as, for example, one or more of coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, and / or baby formula) following storage in such aqueous solution for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0155] In some embodiments, release of a payload component from a microemulsion particle formulation described herein into a solution is delayed as compared to an appropriate reference (e.g., to free payload component and / or to non-emulsified payload component).

[0156] As used herein, the term “diffusion coefficient” refers to an amount of a payload component that diffuses across a unit area per unit time under the influence of a gradient of one unit. In some embodiments, a microemulsion particle formulation of the present disclosure that includes a payload component is characterized in that such payload component displays a reduced diffusion coefficient in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) than does an appropriate reference payload component (e.g., than does free payload component and / or non-emulsified payload component); in some suchembodiments, observed payload component diffusion coefficient is reduced by at least about 10%, at least about 20%, at least about 50%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99.9%, at least about 99.99%, at least about 99.999%, or at least about 99.9999% as compared to such appropriate reference (e.g., to free payload component and / or to non-emulsified payload component).

[0157] In some embodiments, a microemulsion particle formulation of the present disclosure that includes a payload component is characterized in that such payload component displays a reduced diffusion coefficient in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) after such a microemulsion particle formulation has been combined with such aqueous solution and the combination has been stored for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, as compared with an appropriate reference, e g., with free payload component and / or with non-emul sifted payload component).

[0158] In some embodiments, a microemulsion particle formulation of the present disclosure that includes a payload component is characterized in that the payload component maintains a diffusion coefficient that is reduced by at least about 10%, at least about 20%, at least about 50%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99.9%, at least about 99.99%, at least about 99.999%, or at least about 99.9999% as compared to a diffusion coefficient of an appropriate reference (e.g., a free payload component or a non-emulsified payload component) following storage in an aqueous solution (for example, in a beverage such as, for example, in coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0159] In some embodiments, a microemulsion particle formulation of the present disclosure that includes a payload component is characterized in that, when the formulation is combined with an aqueous solution (e.g., with a beverage such as, for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) a concentration equilibrium of the payload component is maintained between particles of the formulation and the aqueous solution with which it is combined (which aqueous solution may be referred to as “exterior” relative to the particles); in some such embodiments, such a concentration equilibrium is maintained for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months (e.g., after combination of the microemulsion particle formulation and the aqueous solution). In some embodiments, a payload component concentration equilibrium is calculated as a ratio of a payload component concentration within particles of the formulation and a payload component concentration in an exterior aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula).

[0160] In some embodiments, a payload component concentration equilibrium is a ratio of about 500:1, about 450: 1, about 400: 1, about 350: 1, about 300: 1, about 250:1, about 200: 1, about 150: 1, about 100: 1, about 75: 1, about 50: 1, about 25: 1, about 10: 1, about 9: 1, about 8: 1, about 7:1, about 6: 1, about 5:1, about 4: 1, about 3:1, about 2: 1, or about 1.5: 1 following storage of a microemulsion of the present disclosure in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, amilk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0161] In some embodiments, a concentration equilibrium is modulated in response to the presence of one or more environmental factors. In some embodiments, a concentration equilibrium is modulated such that a ratio of a payload component concentration within particles of a microemulsion particle formulation and a payload component concentration in an exterior aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented nonalcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) increases in the presence of one or more environmental factors as compared to a ratio in the absence of the one or more environmental factors. In some embodiments, a concentration equilibrium is modulated such that a ratio of a payload component concentration within particles of a microemulsion particle formulation and a payload component concentration in an exterior aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) decreases in the presence of one or more environmental factors as compared to a ratio in the absence of the one or more environmental factors.

[0162] In some embodiments, an environmental factor includes, but is not limited to, an increase or decrease in temperature, an increase or decrease in concentration of the payload component in the aqueous solution, enzymatic digestion, bile salts, pH, microbes, tonicity, shear, pressure, activation energy, sound, or magnetic field.

[0163] In some embodiments, a microemulsion particle formulation of the present disclosure is characterized by delayed release of a payload component into one or more gastrointestinal compartments of a subject that has ingested the microemulsion particle formulation as compared to release observed upon ingestion of an appropriate reference (e.g., of free payload component and / or of non-emulsified payload component). For example, in someembodiments, release of a payload component from a microemulsion particle formulation of the present disclosure is delayed until the microemulsion particle formulation reaches the small intestine of a subject that has ingested the microemulsion particle formulation.

[0164] In some embodiments, a microemulsion particle formulation of the present disclosure increases bioavailability of a payload component in a subject that has ingested the microemulsion particle formulation as compared to that observed for an appropriate reference payload component formulation (e.g., free payload component and / or non-emulsified payload component).

[0165] In some embodiments, a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in a gastrointestinal compartment of a subject that has ingested the microemulsion particle formulation. In some embodiments, a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in an oral cavity of a subject that has ingested the microemulsion particle formulation. In some embodiments, a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in a gastric cavity of a subject that has ingested the microemulsion particle formulation. In some embodiments, a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in a small intestine of a subject that has ingested the microemulsion particle formulation. In some embodiments, a microemulsion particle formulation of the present disclosure is characterized in that release of a payload component is responsive to the presence of one or more digestive enzymes in a colon of a subject that has ingested the microemulsion particle formulation.

[0166] For example, in some embodiments, release of payload component from a provided microemulsion particle formulation described herein is reduced and / or delayed relative to an appropriate reference (e.g., to free payload component and / or to non-emulsified payload component) unless and / or until the provided microemulsion particle formulation encounters such digestive enzyme(s). When relevant digestive enzyme(s) are encountered, release may, in someembodiments, be rapid - including in some embodiments relative to one or more other formulations of the same payload component.

[0167] In some embodiments, a microemulsion particle formulation of the present disclosure includes a payload component that is reversibly modified via chemical conjugation to one or more lipophilic moieties. In some embodiments, a payload component is chemically conjugated to a fat. In some embodiments, a payload component is chemically conjugated to a fatty acid. In some embodiments, a reversibly modified payload component has delayed release from a microemulsion particle (and / or from a microemulsion particle formulation) as compared to a payload component that has not been reversibly modified. In some embodiments, a lipophilic moiety is removed from a payload component to which it is reversibly conjugated upon ingestion of a microemulsion particle of the present disclosure by a subject. In some embodiments, a lipophilic moiety is removed from a payload component to which it is reversibly conjugated by a digestive enzyme present in a gastrointestinal compartment of a subject upon ingestion of a microemulsion particle of the present disclosure by the subject.

[0168] In some embodiments, a microemulsion particle formulation of the present disclosure is characterized by an internal pH of about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, or about 14.

[0169] In some embodiments, a microemulsion particle (and / or a microemulsion particle formulation) of the present disclosure is pH responsive. For example in some embodiments, release of a payload component from a microemulsion particle (and / or from a microemulsion particle formulation) of the present disclosure is enhanced when the microemulsion particle (or microemulsion particle formulation) is exposed to a pH of about 5.5 to 7.5, about 5.75 to 7.5, about 6.0 to 7.5, about 6.25 to 7.5, about 6.5 to 7.5, about 6.75 to 7.5, about 7.0 to 7.5, about 7.25 to 7.5, about 5.5 to 7.25, about 5.75 to 7.25, about 6.0 to 7.25, about 6.25 to 7.25, about 6.5 to 7.25, about 6.75 to 7.25, about 7.0 to 7.25, about 5.5 to 7.0, about 5.75 to 7.0, about 6.0 to 7.0, about 6.25 to 7.0, about 6.5 to 7.0, about 6.75 to 7.0, about 5.5 to 6.75, about 5.75 to 6.75, about 6.0 to 6.75, about 6.25 to 6.75, about 6.5 to 6.75, about 5.5 to 6.5, about 5.75 to 6.5, about 6.0 to 6.5, about 6.25 to 6.5, about 5.5 to 6.25, about 5.75 to 6.25, about 6.0 to 6.25, about 5.5 to 6.0, about 5.75 to 6.0, or about 5.5 to 5.75. In some embodiments, release of a payload component from a microemulsion particle of the present disclosure is reduced when the microemulsionparticle is exposed to a pH of about 1.5 to 3.5, about 1 .75 to 3.5, about 2.0 to 3.5, about 2.25 to 3.5, about 2.5 to 3.5, about 2.75 to 3.5, about 3.0 to 3.5, about 3.25 to 3.5, about 1.5 to 3.25, about 1.75 to 3.25, about 2.0 to 3.25, about 2.25 to 3.25, about 2.5 to 3.25, about 2.75 to 3.25, about 3.0 to 3.25, about 1.5 to 3.0, about 1.75 to 3.0, about 2.0 to 3.0, about 2.25 to 3.0, about 2.5 to 3.0, about 2.75 to 3.0, about 1.5 to 2.75, about 1.75 to 2.75, about 2.0 to 2.75, about 2.25 to 2.75, about 2.5 to 2.75, about 1.5 to 2.5, about 1.75 to 2.5, about 2.0 to 2.5, about 2.25 to 2.5, about 1.5 to 2.25, about 1.75 to 2.25, about 2.0 to 2.25, about 1.5 to 2.0, about 1.75 to 2.0, or about 1.5 to 1.75.

[0170] In some embodiments, release of a payload component from a microemulsion particle (and / or from a microemulsion particle formulation) of the present disclosure is independent of pH and / or is non-responsive to a change in pH.

[0171] In some embodiments, particles of a microemulsion particle formulation of the present disclosure have a same average diameter at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14. In some embodiments, particles of a microemulsion particle formulation of the present disclosure have a same average diameter following storage in an aqueous solution (for example, in a beverage, e g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14, for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0172] In some embodiments, a preparation of microemulsion particles (e.g., a microemulsion particle formulation) of the present disclosure is characterized by a distribution of average diameters (e.g., Dv(10), Dv(20), Dv(30), Dv(40), Dv(50), Dv(60), Dv(70), Dv(80), Dv(90), Dv(99), etc.) that is the same at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14. In some embodiments, a microemulsion particle formulation of the present disclosure is characterized by a same distribution of average diameters (e.g., Dv(10), Dv(20), Dv(30), Dv(40), Dv(50), Dv(60), Dv(70), Dv(80), Dv(90), Dv(99), etc.) following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient- fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14, for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0173] In some embodiments, a microemulsion particle formulation of the present disclosure is characterized by a payload component concentration that is the same at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14. In some embodiments, a microemulsion particle formulation of the present disclosure has a same payload component concentration following storage in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energybeverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14, for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0174] In some embodiments, a microemulsion particle formulation of the present disclosure releases a payload component at a predictable rate upon ingestion of the microemulsion particle by a subject. In some embodiments, a microemulsion particle of the present disclosure releases a payload component upon ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject at a rate that prolongs a pharmacologic, nutritive, and / or cognitive benefit of the payload component as compared to that achieved with an appropriate reference (e.g., by free payload and / or by non-emulsified payload component).

[0175] In some embodiments, a microemulsion particle formulation of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 1 hour of ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject.

[0176] In some embodiments, a microemulsion particle formulation of the present disclosure that has been stored in an aqueous solution (for example, in a beverage, e g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 1 hour of ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject.

[0177] In some embodiments, a microemulsion particle formulation of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 2 hours of ingestion of the microemulsion particle formulation (e g., in a fortified beverage as described herein) by a subject.

[0178] In some embodiments, a microemulsion particle formulation of the present disclosure stored in an aqueous solution (for example, in a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 2 hours of ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject.

[0179] In some embodiments, a microemulsion particle formulation of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 4 hours of ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject.

[0180] In some embodiments, a microemulsion particle formulation of the present disclosure stored in an aqueous solution (for example, a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%,about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 4 hours of ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject.

[0181] In some embodiments, a microemulsion particle formulation of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 6 hours of ingestion of the microemulsion particle formulation (e g., in a fortified beverage as described herein) by a subject.

[0182] In some embodiments, a microemulsion particle formulation of the present disclosure stored in an aqueous solution (for example, in a beverage, e.g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 6 hours of ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject.

[0183] In some embodiments, a microemulsion particle formulation of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 8 hours of ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject.

[0184] In some embodiments, a microemulsion particle formulation of the present disclosure stored in an aqueous solution (for example, in a beverage, e g., coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 8 hours of ingestion of the microemulsion particle formulation (e.g., in a fortified beverage as described herein) by a subject.Fortified Beverages

[0185] The present disclosure additionally provides beverages that have been fortified with microemulsion particle formulations as described herein, e.g., including a payload component, a fatty acid component, a surfactant component, an antioxidant component, and a stabilizing component.

[0186] Provided fortified beverage compositions therefore include an aqueous phase (e g., a base beverage) and a particle phase (e.g., that is or comprises particles of a microemulsion particle formulation).

[0187] In some embodiments, a particular payload (e.g., caffeine) is present in both the particle phase and the aqueous phase of a provided fortified beverage.

[0188] In certain embodiments, a formulated beverage is characterized by one or more features of payload release (e.g., extended release) as described herein.

[0189] In certain embodiments, a provided formulated beverage has been stored for a period of time (e.g., as set forth herein); in certain such embodiments, such a stored formulated beverage is characterized by one or more features of payload release that is reasonably comparable to that observed for the fortified beverage prior to such storage.

[0190] In some embodiments, a formulation of the present disclosure is added to a base beverage to produce the fortified beverage. In some embodiments, a base beverage is selected from, but not limited to, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula. In some embodiments, a base beverage is Monster ™ or Red Bull™ energy drink. In some embodiments, a base beverage is oatmilk or Oatly™ beverage.

[0191] In some embodiments, a fortified beverage of the present disclosure includes about 0.1 w / v% to 5 w / v% of a payload component. For example, in some embodiments, a fortified beverage of the present disclosure includes about 0.1 w / v% to 5 w / v%, about 0.25 w / v% to 5 w / v%, about 0.5 w / v% to 5 w / v%, about 0.75 w / v% to 5 w / v%, about 1 w / v% to 5 w / v%, about 1.25 w / v% to 5 w / v%, about 1.5 w / v% to 5 w / v%, about 1.75 w / v% to 5 w / v%, about 2.0 w / v% to 5 w / v%, about 2.25 w / v% to 5 w / v%, about 2.5 w / v% to 5 w / v%, about 2.75 w / v% to 5w / v%, about 3 w / v% to 5 w / v%, about 3.25 w / v% to 5 w / v%, about 3.5 w / v% to 5 w / v%, about 3.75 w / v% to 5 w / v%, about 4 w / v% to 5 w / v%, about 4.25 w / v% to 5 w / v%, about 4.5 w / v% to 5 w / v%, about 4.75 w / v% to 5 w / v%, about 0.1 w / v% to 4.5 w / v%, about 0.25 w / v% to 4.5 w / v%, about 0.5 w / v% to 4.5 w / v%, about 0.75 w / v% to 4.5 w / v%, about 1 w / v% to 4.5 w / v%, about 1.25 w / v% to 4.5 w / v%, about 1.5 w / v% to 4.5 w / v%, about 1.75 w / v% to 4.5 w / v%, about 2.0 w / v% to 4.5 w / v%, about 2.25 w / v% to 4.5 w / v%, about 2.5 w / v% to 4.5 w / v%, about 2.75 w / v% to 4.5 w / v%, about 3 w / v% to 4.5 w / v%, about 3.25 w / v% to 4.5 w / v%, about 3.5 w / v% to4.5 w / v%, about 3.75 w / v% to 4.5 w / v%, about 4 w / v% to 4.5 w / v%, about 4.25 w / v% to 4.5 w / v%, about 0.1 w / v% to 4 w / v%, about 0.25 w / v% to 4 w / v%, about 0.5 w / v% to 4 w / v%, about 0.75 w / v% to 4 w / v%, about 1 w / v% to 4 w / v%, about 1.25 w / v% to 4 w / v%, about 1.5 w / v% to 4 w / v%, about 1.75 w / v% to 4 w / v%, about 2.0 w / v% to 4 w / v%, about 2.25 w / v% to 4 w / v%, about 2.5 w / v% to 4 w / v%, about 2.75 w / v% to 4 w / v%, about 3 w / v% to 4 w / v%, about 3.25 w / v% to 4 w / v%, about 3.5 w / v% to 4 w / v%, about 3.75 w / v% to 4 w / v%, about 0.1 w / v% to 3.5 w / v%, about 0.25 w / v% to 3.5 w / v%, about 0.5 w / v% to 3.5 w / v%, about 0.75 w / v% to3.5 w / v%, about 1 w / v% to 3.5 w / v%, about 1.25 w / v% to 3.5 w / v%, about 1.5 w / v% to 3.5 w / v%, about 1.75 w / v% to 3.5 w / v%, about 2.0 w / v% to 3.5 w / v%, about 2.25 w / v% to 3.5 w / v%, about 2.5 w / v% to 3.5 w / v%, about 2.75 w / v% to 3.5 w / v%, about 3 w / v% to 3.5 w / v%, about 3.25 w / v% to 3.5 w / v%, about 0.1 w / v% to 3 w / v%, about 0.25 w / v% to 3 w / v%, about 0.5 w / v% to 3 w / v%, about 0.75 w / v% to 3 w / v%, about 1 w / v% to 3 w / v%, about 1.25 w / v% to 3 w / v%, about 1.5 w / v% to 3 w / v%, about 1.75 w / v% to 3 w / v%, about 2.0 w / v% to 3 w / v%, about 2.25 w / v% to 3 w / v%, about 2.5 w / v% to 3 w / v%, about 2.75 w / v% to 3 w / v%, about 0.1 w / v% to 2.5 w / v%, about 0.25 w / v% to 2.5 w / v%, about 0.5 w / v% to 2.5 w / v%, about 0.75 w / v% to 2.5 w / v%, about 1 w / v% to 2.5 w / v%, about 1.25 w / v% to 2.5 w / v%, about 1.5 w / v% to2.5 w / v%, about 1.75 w / v% to 2.5 w / v%, about 2.0 w / v% to 2.5 w / v%, about 2.25 w / v% to 2.5 w / v%, about 0. 1 w / v% to 2 w / v%, about 0.25 w / v% to 2 w / v%, about 0.5 w / v% to 2 w / v%, about 0.75 w / v% to 2 w / v%, about 1 w / v% to 2 w / v%, about 1.25 w / v% to 2 w / v%, about 1.5 w / v% to 2 w / v%, about 1.75 w / v% to 2 w / v%, about 0.1 w / v% to 1.5 w / v%, about 0.25 w / v% to1.5 w / v%, about 0.5 w / v% to 1.5 w / v%, about 0.75 w / v% to 1.5 w / v%, about 1 w / v% to 1.5 w / v%, about 1.25 w / v% to 1.5 w / v%, about 0.1 w / v% to 1 w / v%, about 0.25 w / v% to 1 w / v%, about 0.5 w / v% to 1 w / v%, about 0.75 w / v% to 1 w / v%, about 0.1 w / v% to 0.5 w / v%, or about 0.25 w / v% to 0.5 w / v of a payload component.

[0192] In some embodiments, a payload component includes lutein, vitamin D, zeaxanthin, vitamin A, caffeine, vitamin B 12, creatine, creatine ethyl ester, creatine phosphate, tannic acid, theaflavin, theaflavin gallate, thearubigins, ellagitannins, catechins, epigallocatechin gallate, gallic acid and its alkyl esters, glucose, curcurmin, quercetin, rutin, naringenin, fatty acids, a nutritive and / or bioactive peptide, a feruloylated arabinoxylan-enriched fiber, heat- treated whey protein isolate, sodium caseinate, collagen, gelatin, rice bran, wheat bran, resistant corn dextrin, resistant potato dextrin or a combination thereof. In some embodiments, the payload component provides a nutritional, health, and / or stimulatory benefit to a subject when the formulation is consumed by the subject.

[0193] In some embodiments, a fortified beverage of the present disclosure has a turbidity no greater than about 25 NTU, about 50 NTU, about 75 NTU, about 100 NTU, about 125 NTU, about 150 NTU, about 175 NTU, about 200 NTU, about 225 NTU, about 250 NTU, about 275 NTU, about 300 NTU, about 325 NTU, about 350 NTU, about 375 NTU, about 400 NTU, about 425 NTU, about 450 NTU, about 475 NTU, about 500 NTU, about 525 NTU, about 550 NTU, about 575 NTU, about 600 NTU, about 625 NTU, about 650 NTU, about 675 NTU, about 700 NTU, about 725 NTU, or about 750 NTU.

[0194] In some embodiments a fortified beverage includes about 0.001 to 0.1 mg / ml of a formulation having one or more microsome particles wherein the one or more microsome particles incorporate a payload component, a fatty acid component, a surfactant component, an antioxidant component, and a stabilizing component. In some embodiments, a fortified beverage of the present disclosure includes about 0.001 to 0.1 mg / ml, about 0.005 to 0. 1 mg / ml, about 0.01 to 0.1 mg / ml, about 0.015 to 0.1 mg / ml, about 0.02 to 0.1 mg / ml, about 0.025 to 0.1 mg / ml, about 0.03 to 0.1 mg / ml, about 0.035 to 0.1 mg / ml, about 0.04 to 0.1 mg / ml, about 0.045 to 0.1 mg / ml, about 0.05 to 0.1 mg / ml, about 0.055 to 0. 1 mg / ml, about 0.06 to 0.1 mg / ml, about 0.065 to 0.1 mg / ml, about 0.07 to 0.1 mg / ml, about 0.075 to 0.1 mg / ml, about 0.08 to 0.1 mg / ml, about 0.085 to 0.1 mg / ml, about 0.09 to 0.1 mg / ml, about 0.095 to 0.1 mg / ml, about 0.001 to 0.1 mg / ml, about 0.005 to 0.1 mg / ml, about 0.01 to 0.075 mg / ml, about 0.015 to 0.075 mg / ml, about 0.02 to 0.075 mg / ml, about 0.025 to 0.075 mg / ml, about 0.03 to 0.075 mg / ml, about 0.035 to 0.075 mg / ml, about 0.04 to 0.075 mg / ml, about 0.045 to 0.075 mg / ml, about 0.05 to 0.075 mg / ml, about 0.055 to 0.075 mg / ml, about 0.06 to 0.075 mg / ml, about 0.065 to 0.075 mg / ml,about 0.07 to 0.075 mg / ml, about 0.001 to 0.05 mg / ml, about 0.005 to 0.05 mg / ml, about 0.01 to 0.05 mg / ml, about 0.015 to 0.05 mg / ml, about 0.02 to 0.05 mg / ml, about 0.025 to 0.05 mg / ml, about 0.03 to 0.05 mg / ml, about 0.035 to 0.05 mg / ml, about 0.04 to 0.05 mg / ml, or about 0.045 to 0.05 mg / ml of a formulation having one or more microsome particles wherein the one or more microsome particles incorporate a payload component, a fatty acid component, a surfactant component, an antioxidant component, and a stabilizing component.

[0195] In some embodiments, a fortified beverage of the present disclosure has enhanced stability of a payload component when stored in a base beverage as compared to an appropriate reference payload component formulation (e.g., free payload component and / or non-emulsified payload component). In some embodiments, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% of a payload component is recoverable from a fortified beverage disclosed herein after storage for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months. For example, in some embodiments, at least 75% of a payload component is recoverable from a fortified beverage of the present disclosure after about 16 weeks of storage.

[0196] In some embodiments, release of a payload component from a fortified beverage described herein is delayed as compared to an appropriate reference payload component formulation (e.g., free payload component and / or non-emulsified payload component). In some embodiments, a base beverage comprises a concentration of a payload component that is less than the concentration of the payload component in a microsome particle of the present disclosure, thereby establishing a concentration gradient across the liposomal membrane. In some embodiments, a concentration of a payload component in a base beverage is in equilibrium with a concentration of the payload component in a microsome particle of the present disclosure. In some embodiments, a concentration of a payload component in a base beverage contributes todelayed release of the payload component from a microsome particle of the present disclosure as compared to the release of the payload component from the microsome particle into a base beverage that does not contain any concentration of the payload component.

[0197] In some embodiments, a fortified beverage of the present disclosure has an amount of payload component in the base beverage thereby establishing a payload component concentration gradient across liposomal membranes of its one or more constituent microsome particles. In some embodiments, a concentration gradient contributes to the delayed release of a payload component from a microsome particle of the present disclosure into one or more gastrointestinal compartment of a subject that has ingested the fortified beverage. For example, in some embodiments, a payload component concentration gradient of a fortified beverage disclosed herein contributes to the delayed release of the payload component into the small intestine of a subject that has ingested the fortified beverage. In some embodiments, a payload component concentration gradient of a fortified beverage disclosed herein contributes to the increased bioavailability of the payload component.

[0198] In some embodiments, a fortified beverage of the present disclosure includes microemulsion particles (e.g., a microemulsion particle formulation) that are miscible in a base beverage. In some embodiments, a base beverage is selected from, but is not limited to, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula.

[0199] In some embodiments, a microemulsion particle formulation of the present disclosure does not form aggregates, flocculates, bezoars, or sediments when added to a base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula). In some embodiments, a microemulsion particle formulation of the present disclosure does not form aggregates, flocculates, bezoars, or sediments when added to a base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) following storage for a period of at least 1 day, at least 2 days, at least 3 days, atleast 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0200] In some embodiments, a fortified beverage of the present disclosure includes microemulsion particles (e.g., a microemulsion particle formulation) having a reduced diffusion coefficient of a payload component in a base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) by at least about 10%, at least about 20%, at least about 50%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99.9%, at least about 99.99%, at least about 99.999%, or at least about 99.9999% as compared to a diffusion coefficient of free payload component (e.g., non-emulsified payload component) in the base beverage.

[0201] In some embodiments, a fortified beverage of the present disclosure includes microemulsion particles (e.g., a microemulsion particle formulation) that maintain a reduced diffusion coefficient of a payload component in a base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) following storage in the base beverage for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months as compared to a diffusion coefficient of a reference control or free payload component (e.g., nonemulsified payload component).

[0202] In some embodiments, a fortified beverage of the present disclosure includes microemulsion particles (e g., a microemulsion particle formulation) that maintain a diffusion coefficient of a payload component that is reduced by at least about 10%, at least about 20%, at least about 50%, at least about 75%, at least about 80%, at least about 85%, at least about 90%,at least about 95%, at least about 99.9%, at least about 99.99%, at least about 99.999%, or at least about 99.9999% as compared to a diffusion coefficient of a reference control or free payload component (e.g., non-emulsified payload component) following storage in a base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0203] In some embodiments, a fortified beverage of the present disclosure includes microemulsion particles (e.g., a microemulsion particle formulation) that maintain a payload component concentration equilibrium between the interior of the microemulsion particle and an exterior base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months. In some embodiments, a payload component concentration equilibrium is calculated as a ratio of a payload component concentration within the interior of a microemulsion particle and a payload component concentration in an exterior base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula). In some embodiments, a payload component concentration equilibrium is a ratio of about 500:1, about 450: 1, about 400: 1, about 350: 1, about 300:1, about 250:1, about 200: 1, about 150: 1, about 100: 1, about 75: 1, about 50: 1, about 25: 1, about 10: 1, about 9: 1, about 8: 1, about 7:1 , about 6: 1 , about 5:1, about 4: 1, about 3:1, about 2: 1, or about 1.5: 1 following storage of a microemulsion of the present disclosure in a base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage,water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0204] In some embodiments, a concentration equilibrium is modulated in response to the presence of one or more environmental factors. In some embodiments, a concentration equilibrium is modulated such that a ratio of a payload component concentration within the interior of a microemulsion particle and a payload component concentration in an exterior base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) increases in the presence of one or more environmental factors as compared to a ratio in the absence of the one or more environmental factors. In some embodiments, a concentration equilibrium is modulated such that a ratio of a payload component concentration within the interior of a microemulsion particle and a payload component concentration in an exterior base beverage (for example, coconut water, sparkling water, fermented non-alcoholic beverages, alcoholic beverages, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or baby formula) decreases in the presence of one or more environmental factors as compared to a ratio in the absence of the one or more environmental factors. In some embodiments, an environmental factor includes, but is not limited to, an increase or decrease in temperature, an increase or decrease in concentration of the payload component in the aqueous solution, enzymatic digestion, bile salts, pH, microbes, tonicity, shear, pressure, activation energy, sound, or magnetic field.

[0205] In some embodiments, a fortified beverage of the present disclosure includes microemulsion particles (e.g., a microemulsion particle formulation) characterized by an internal pH that is different than the pH of a base beverage of the fortified beverage. In some embodiments, an internal pH of such microemulsion particles (e.g., a microemulsion particleformulation) is about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, or about 14.

[0206] In some embodiments, a fortified beverage of the present disclosure includes microemulsion particles (e.g., a microemulsion particle formulation) that has delayed release of a payload component into one or more gastrointestinal compartments of a subject that has ingested the fortified beverage as compared to a reference control or free payload component (e.g., nonemulsified payload component). For example, in some embodiments, release of a payload component from a microemulsion particle is delayed until the microemulsion particle reaches the small intestine of a subject that has ingested a fortified beverage of the present disclosure. In some embodiments, a microemulsion particle of the present disclosure increases bioavailability of a payload component in a subject that has ingested a fortified beverage as compared to an appropriate reference (e.g., a subject that has ingested the same beverage containing free payload and / or to the same beverage containing non-emulsified payload component).

[0207] In some embodiments, a fortified beverage of the present disclosure (i.e., including a microemulsion particle formulation described herein) is characterized in that release of a payload component from the fortified beverage is responsive to the presence of one or more digestive enzymes which may be found, for example, in a gastrointestinal compartment, in an oral cavity, in a gastric cavity, in a small intestine, and / or in a colon of a subject that has ingested the fortified beverage. For example, in some embodiments, release of a payload component from a fortified beverage described herein is reduced and / or delayed relative to an appropriate reference (e.g., to the same beverage containing a free payload component and / or to the same beverage containing a non-emulsified payload component) unless and / or until the fortified beverage encounters such digestive enzyme(s). When relevant digestive enzyme(s) are encountered, release may, in some embodiments, be rapid - including in some embodiments relative to the same beverage containing one or more other formulations of the same payload component.

[0208] In some embodiments, a fortified beverage of the present disclosure is characterized in that release of a payload component from the fortified beverage is pH responsive. For example in some embodiments, release of a payload component from a fortified beverage of the present disclosure is enhanced when the beverage is exposed to a pH of about 5.5to 7.5, about 5.75 to 7.5, about 6.0 to 7.5, about 6.25 to 7.5, about 6.5 to 7.5, about 6.75 to 7.5, about 7.0 to 7.5, about 7.25 to 7.5, about 5.5 to 7.25, about 5.75 to 7.25, about 6.0 to 7.25, about6.25 to 7.25, about 6.5 to 7.25, about 6.75 to 7.25, about 7.0 to 7.25, about 5.5 to 7.0, about 5.75 to 7.0, about 6.0 to 7.0, about 6.25 to 7.0, about 6.5 to 7.0, about 6.75 to 7.0, about 5.5 to 6.75, about 5.75 to 6.75, about 6.0 to 6.75, about 6.25 to 6.75, about 6.5 to 6.75, about 5.5 to 6.5, about 5.75 to 6.5, about 6.0 to 6.5, about 6.25 to 6.5, about 5.5 to 6.25, about 5.75 to 6.25, about 6.0 to6.25, about 5.5 to 6.0, about 5.75 to 6.0, or about 5.5 to 5.75. In some embodiments, release of a payload component from a fortified beverage of the present disclosure is reduced when a fortified beverage is exposed to a pH of about 1.5 to 3.5, about 1.75 to 3.5, about 2.0 to 3.5, about 2.25 to 3.5, about 2.5 to 3.5, about 2.75 to 3.5, about 3.0 to 3.5, about 3.25 to 3.5, about 1.5 to 3.25, about 1.75 to 3.25, about 2.0 to 3.25, about 2.25 to 3.25, about 2.5 to 3.25, about 2.75 to3.25, about 3.0 to 3.25, about 1.5 to 3.0, about 1.75 to 3.0, about 2.0 to 3.0, about 2.25 to 3.0, about 2.5 to 3.0, about 2.75 to 3.0, about 1.5 to 2.75, about 1.75 to 2.75, about 2.0 to 2.75, about2.25 to 2.75, about 2.5 to 2.75, about 1.5 to 2.5, about 1.75 to 2.5, about 2.0 to 2.5, about 2.25 to 2.5, about 1.5 to 2.25, about 1.75 to 2.25, about 2.0 to 2.25, about 1.5 to 2.0, about 1.75 to 2.0, or about 1.5 to 1.75.

[0209] In some embodiments, release of a payload component from a fortified beverage of the present disclosure is independent of pH (e.g., is non-responsive to a change in pH). In some embodiments, a fortified beverage of the present disclosure is characterized in that microemulsion particles within in have a same average diameter at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14. In some embodiments, a fortified beverage of the present disclosure is characterized in that microemulsion particles within it have a same average diameter following storage of the fortified beverage (which may for example, be fortified coconut water, fortified sparkling water, a fortified fermented non-alcoholic beverage, a fortified alcoholic beverage, a fortified energy beverage, fortified water, fortified nutrient- fortified water, a fortified carbonated drink, fortified coffee, fortified tea, fortified juice, fortified milk, fortified milk alternative, or fortified baby formula) at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6,about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14, for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0210] In some embodiments, a fortified beverage of the present disclosure includes a plurality of microemulsion particles that have a distribution of average diameters (e.g., Dv(10), Dv(20), Dv(30), Dv(40), Dv(50), Dv(60), Dv(70), Dv(80), Dv(90), Dv(99), etc.) that is the same at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14. In some embodiments, a fortified beverage of the present disclosure includes a plurality of microemulsion particles that have a same distribution of average diameters (e.g., Dv(10), Dv(20), Dv(30), Dv(40), Dv(50), Dv(60), Dv(70), Dv(80), Dv(90), Dv(99), etc.) following storage of the fortified beverage (which may for example, be fortified coconut water, fortified sparkling water, a fortified fermented non-alcoholic beverage, a fortified alcoholic beverage, a fortified energy beverage, fortified water, fortified nutrient-fortified water, a fortified carbonated drink, fortified coffee, fortified tea, fortified juice, fortified milk, fortified milk alternative, or fortified baby formula) at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14, for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0211] In some embodiments, a fortified beverage of the present disclosure is characterized by a payload component concentration in microemulsion particles within the fortified beverage that is the same at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14. In some embodiments, a fortified beverage of the present disclosure is characterized by a payload component concentration following storage of the fortified beverage (which may for example, be fortified coconut water, fortified sparkling water, a fortified fermented non-alcoholic beverage, a fortified alcoholic beverage, a fortified energy beverage, fortified water, fortified nutrient-fortified water, a fortified carbonated drink, fortified coffee, fortified tea, fortified juice, fortified milk, fortified milk alternative, or fortified baby formula) at about pH 1 to about pH 2, about pH 2 to about pH 3, about pH 3 to about pH 4, about pH 4 to about pH 5, about pH 5 to about pH 6, about pH 6 to about pH 7, about pH 7 to about pH 8, about pH 8 to about pH 9, about pH 9 to about pH 10, about pH 10 to about pH 11, about pH 11 to about pH 12, about pH 12 to about pH 13, and about pH 13 to about pH 14, for a period of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months.

[0212] In some embodiments, a fortified beverage of the present disclosure releases a payload component at a predictable rate upon ingestion of the fortified beverage by a subject. In some embodiments, a fortified beverage of the present disclosure releases a payload component upon ingestion of the fortified beverage by a subject at a rate that prolongs a pharmacologic, nutritive, and / or cognitive benefit received by the ingesting subject as compared with an appropriate reference, such as that received upon ingestion of an otherwise comparable beverage containing free payload component (e.g., non-emulsified payload component).

[0213] In some embodiments, a fortified beverage of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% toabout 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 1 hour of ingestion of the fortified beverage by a subject.

[0214] In some embodiments, a fortified beverage of the present disclosure stored for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% toabout 30%, or about 10% to about 20% of a payload component incorporated therein within 1 hour of ingestion of the fortified beverage by a subject.

[0215] In some embodiments, a fortified beverage of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 2 hours of ingestion of the fortified beverage by a subject.

[0216] In some embodiments, a fortified beverage of the present disclosure stored for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% toabout 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 2 hours of ingestion of the fortified beverage by a subject.

[0217] In some embodiments, a fortified beverage of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 4 hours of ingestion of the fortified beverage by a subject.

[0218] In some embodiments, a fortified beverage of the present disclosure stored for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% toabout 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 4 hours of ingestion of the fortified beverage by a subject.

[0219] In some embodiments, a fortified beverage of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 6 hours of ingestion of the fortified beverage by a subject.

[0220] In some embodiments, a fortified beverage of the present disclosure stored for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 6 hours of ingestion of the fortified beverage by a subject.

[0221] In some embodiments, a fortified beverage of the present disclosure releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 8 hours of ingestion of the fortified beverage by a subject.

[0222] In some embodiments, a fortified beverage of the present disclosure stored for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 12 weeks, at least 16 weeks, at least 6 months, at least 8 months, at least 10 months, at least 12 months, at least 16 months, at least 20 months, or at least 24 months, releases about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, about 80% to about 100%, about 90% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about 90%, about 50% to about 90%, about 60% to about 90%, about 70% to about 90%, about 80% to about 90%, about 10% to about 80%, about 20% to about 80%, about 30% to about 80%, about 40% to about 80%, about 50% to about 80%, about 60% to about 80%, about 70% to about 80%, about 10% to about 70%, about 20% to about 70%, about 30% to about 70%, about 40% to about 70%, about 50% to about 70%, about 60% to about 70%, about 10% to about 60%, about 20% to about 60%, about 30% to about 60%, about 40% to about 60%, about 50% to about 60%, about 10% to about 50%, about 20% to about 50%, about 30% to about 50%, about 40% to about 50%, about 10% to about 40%, about 20% to about 40%, about 30% to about 40%, about 10% to about 30%, about 20% to about 30%, or about 10% to about 20% of a payload component incorporated therein within 8 hours of ingestion of the fortified beverage by a subject.Methods of Preparation

[0223] The present disclosure additionally provides technologies for manufacturing and / or characterizing microemulsion particle formulations and / or fortified beverages that include them.

[0224] For example, among other things, the present disclosure provides methods of fortifying a beverage, where, in some embodiments, such methods include steps of i) providing a microemulsion particle formulation; and ii) mixing the microemulsion particle formulation with the beverage to produce a fortified beverage.

[0225] In some embodiments, the microemulsion particle formulation provided for fortifying the beverage includes one or more microemulsion particle and at least 80 wt% water, and the one or more microemulsion particles comprises:0.01 wt% to 0.13 wt% of a pay load component;0.1 wt% to 2 wt% of a fatty component;14 wt% to 20 wt% of a surfactant component;0.1 wt% to 2 wt% of an antioxidant component; and0.1 wt% to 4 wt% of a stabilizing component.

[0226] In some embodiments, step i) providing a microemulsion particle formulation includes: i) preparing an aqueous phase; ii) preparing an oil phase; and iii) adding the aqueous phase to the oil phase to produce the one or more microemulsion particles.

[0227] In some such embodiments, step i) preparing an aqueous phase includes adjusting the pH of the aqueous phase. In some embodiments, step i) preparing an aqueous phase includes mixing water and the antioxidant component, and step ii) preparing an oil phase includes mixing the payload component, the oil component, the surfactant component, and the stabilizing component. In some embodiments, a payload component is a fat-soluble / hydrophobic compound. In some embodiments, a payload component includes, but is not limited to, lutein, vitamin D, zeaxanthin, vitamin A, caffeine, vitamin Bl 2, creatine, creatine ethyl ester, creatine phosphate, tannic acid, theaflavin, theaflavin gallate, thearubigins, ellagitannins, catechins, epigallocatechin gallate, gallic acid and its alkyl esters, glucose, curcurmin, quercetin, rutin, naringenin, fatty acids, a nutritive and / or bioactive peptide, a feruloylated arabinoxylan-enriched fiber, heat-treated whey protein isolate, sodium caseinate, collagen, gelatin, rice bran, wheat bran, resistant corn dextrin, resistant potato dextrin or a combination thereof.

[0228] In some embodiments, step i) preparing an aqueous phase includes mixing water, an antioxidant component, and a payload component, and step ii) preparing an oil phase includesmixing an oil component, a surfactant component, and a stabilizing component. In some embodiments, a payload component is a water-soluble / hydrophilic compound. In some embodiments, a payload component includes, but is not limited to, caffeine. In some embodiments, a payload component includes, but is not limited to, creatine.

[0229] In some embodiments, step i) preparing an aqueous phase includes mixing water, a payload component, and a surfactant component, and step ii) preparing an oil phase includes mixing an oil component, an antioxidant component, and a stabilizing component. In some embodiments, a payload component is a water-soluble / hydrophilic compound. In some embodiments, a payload component includes, but is not limited to, caffeine. In some embodiments, a payload component includes, but is not limited to, creatine.

[0230] In some embodiments, step i) preparing an aqueous phase includes mixing water, a payload component, a surfactant component, and a stabilizing component, and step ii) preparing an oil phase includes mixing an oil component, and an antioxidant component. In some embodiments, a payload component is a water-soluble / hydrophilic compound. In some embodiments, a payload component includes, but is not limited to, caffeine. In some embodiments, a payload component includes, but is not limited to, creatine.

[0231] In some embodiments, step i) preparing an aqueous phase includes mixing water, a payload component, a surfactant component, an antioxidant component, and a stabilizing component, and step ii) preparing an oil phase includes mixing the oil component. In some embodiments, a payload component is a water-soluble / hydrophilic compound. In some embodiments, a payload component includes, but is not limited to, caffeine. In some embodiments, a payload component includes, but is not limited to, creatine.

[0232] In some embodiments, step i) preparing an aqueous phase includes mixing water and one or more payload component(s) followed by the adjustment of pH prior to addition of one or more surfactant component(s), antioxidant component(s), and / or stabilizing component(s). In some such embodiments, the pH of said aqueous phase is adjusted to about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, or about 14, prior to addition of one or more surfactant component(s), antioxidant component(s), and / or stabilizing component(s).

[0233] In some embodiments, an oil phase is heated to about 65 °C to 75 °C before step iii). For example, in some embodiments, an oil phase is heated to about 65 °C, about 66 °C, about 67 °C, about 68 °C, about 69 °C, about 70 °C, about 71 °C, about 72 °C, about 73 °C, about 74 °C, or about 75 °C. In some embodiments, an oil phase is heated for about 15 minutes to 60 minutes. For example, in some embodiments, an oil phase is heated for about 15 minutes to 60 minutes, about 30 minutes to 60 minutes, about 45 minutes to 60 minutes, about 15 minutes to 45 minutes, about 30 minutes to 45 minutes, or about 15 minutes to 30 minutes. In some embodiments, an oil phase is heated for about 15 minutes, about 30 minutes, about 45 minutes, or about 60 minutes.

[0234] In some embodiments, step iii) adding an aqueous phase to an oil phase includes adding the aqueous phase dropwise to the oil phase on a stirring plate. In some embodiments, an aqueous phase and oil phase are stirred for about 15 minutes to 60 minutes, about 30 minutes to 60 minutes, about 45 minutes to 60 minutes, about 15 minutes to 45 minutes, about 30 minutes to 45 minutes, or about 15 minutes to 30 minutes.

[0235] In some embodiments, step iii) adding an aqueous phase to an oil phase includes mixing the oil phase with the aqueous phase at a ratio of about 1 : 1 v / v to 1 : 10 v / v. For example, in some embodiments step iii) adding an aqueous phase to an oil phase includes mixing the oil phase with the aqueous phase at a ratio of about 1 : 1 v / v to 1 : 10 v / v, about 1 :2 v / v to 1 : 10 v / v, about 1 :3 v / v to 1 : 10 v / v, about 1 :4 v / v to 1 : 10 v / v, about 1 :5 v / v to 1 : 10 v / v, about 1 :6 v / v to 1 : 10 v / v, about 1:7 v / v to 1 :10 v / v, about 1 :8 v / v to 1 : 10 v / v, about 1 :9 v / v to 1: 10 v / v, about 1 : 1 v / v to 1 :8 v / v, about 1 :2 v / v to 1 :8 v / v, about 1 :3 v / v to 1 :8 v / v, about 1 :4 v / v to 1 :8 v / v, about 1 :5 v / v to 1 :8 v / v, about 1 :6 v / v to 1 :8 v / v, about 1 :7 v / v to 1 :8 v / v, about 1 : 1 v / v to 1 :6 v / v, about 1 :2 v / v to 1 :6 v / v, about 1 :3 v / v to 1:6 v / v, about 1 :4 v / v to 1 :6 v / v, about 1.5 v / v to 1.6 v / v, about 1 : 1 v / v to 1 :4 v / v, about 1 :2 v / v to 1 :4 v / v, about 1 :3 v / v to 1 :4 v / v, or about 1 : 1 v / v to 1 :2 v / v. In some embodiments, step iii) adding an aqueous phase to an oil phase includes mixing the oil phase with the aqueous phase at a ratio of about 1 : 1 v / v, about 1 :2 v / v, about 1 :3 v / v, about 1 :4 v / v, about 1 :5 v / v, about 1 :6 v / v, about 1 :7 v / v, about 1 :8 v / v, about 1 :9 v / v, or about 1 : 10 v / v. For example, in some embodiments, step iii) adding an aqueous phase to an oil phase includes mixing the oil phase with the aqueous phase at a ratio of about 1:4 v / v.

[0236] In some embodiments, a beverage is selected from, but not limited to, an energy beverage, water, nutrient-fortified water, a carbonated drink, coffee, tea, juice, milk, a milk alternative, or a baby formula. In some embodiments, a beverage component is Monster ™ or Red Bull™ energy drink. In some embodiments, a beverage component is oatmilk or Oatly™ beverage.

[0237] In some embodiments, methods of preparing a microemulsion particle described herein further includes resizing the microemulsion particle by gas pressure extrusion, sonication, microfluidic mixing, or a combination thereof, after step iii).

[0238] In some embodiments, methods of preparing a microemulsion particle described herein further includes purifying the microemulsion particle by size-exclusion filtration, centrifugal filtration, tangential flow filtration, or a combination thereof, after step iii).

[0239] In some embodiments, methods of preparing a microemulsion particle described herein further includes concentrating the microemulsion particle by tangential flow filtration, rotary evaporation, centrifugal filtration, or a combination thereof.

[0240] In some embodiments, methods of preparing a microemulsion particle described herein further includes drying the microemulsion particle in the presence of a structural protectant. In some embodiments, the microemulsion particle is dried by lyophilization or spraydrying. In some embodiments, a microemulsion particle of the present disclosure is dried in the presence of sucrose, trehalose, sorbitol, or a combination thereof.EXEMPLIFICATION

[0241] The following examples are provided as illustration and are not intended to be limiting with respect to any subject matter disclosed herein.Example 1: Microemulsion Particle Formulations

[0242] The present example demonstrates certain microemulsion particle formulations comprising lutein, vitamin D2, and / or vitamin B 12 as a payload component.

[0243] Microemulsion particle formulations of the present example were prepared according to methods disclosed herein. Microemulsion particle formulation compositions of the present example are presented in TABLES 1A-1C.

[0244] Exemplary microemulsion particle formulations comprising lutein or vitamin D2 were prepared by self-emulsification. First, a payload component was weighed and added into an oil phase comprising a lipid component, a surfactant component, and an excipient component. The mixture was well mixed and heated up to 70°C for at least 30min. Next, the oil phase was mixed with an aqueous phase at an oil phase: aqueous phase ratio ranging from 1 :4 v / v to 1 :5 v / v. The aqueous phase was added dropwise into the oil phase on a stirring plate. This oil phase / aqueous phase mixture was stirred for at least 30min. During this time, the mixture became transparent, indicating that a homogeneous suspension had formed. This homogenous suspension was a microemulsion particle formulation in accordance with the present disclosure.TABLE 1A. Compositions of Microemulsion Particle Formulations Comprising LuteinTABLE IB. Compositions of Microemulsion Particle Formulations Comprising Vitamin D2

[0245] Exemplary microemulsion particle formulations comprising vitamin B 12 were prepared by a double microemulsion method, sometimes referred to as a “two-step” selfemulsification method. In the first step, vitamin B12 powder was weighed and dissolved in water to form a primary water / oil (“W / O”) microemulsion by a water titration method. After full dissolution of vitamin B12 in water, Kolliphor EL was added and mixed well. The mixture was heated at 70°C for at least 30 min. Next, isoamyl acetate and ethanol was added dropwise at the same heating condition under magnetic stirring with 500 rpm. This mixture then underwent a transition from a transparent solution to a turbid solution and then back to a transparent solution as the isoamyl acetate and ethanol was added continuously with stirring. After it became transparent again, the primary W / O microemulsion was formed. It was then cooled to room temperature with continuous stirring. In the second step, the W / O microemulsion blended with extra amount of Kolliphor EL and ethanol was dispersed in an external aqueous phase to form double microemulsion. The mixture was stirred for at least 30 min to form a homogeneous suspension.TABLE 1C. Compositions of Microemulsion Particle Formulations Comprising Vitamin B12Example 2: Particle Sizes and Particle Size Distributions

[0246] Particle sizes and particle size distributions of particles in microemulsion particle formulations were characterized using a Nanotemper Prometheus Panta instrument. Samples of OmniActive™ products (z.e., non-microemulsion particle formulations) were also tested as a comparison to exemplary microemulsion particle formulations. Formulations were included inwater, Red Bull™, Monster™, or Rockstar™ for particle size characterization and comparison to an Omni Active™ Lutemax 2020 particle formulation control.

[0247] Samples of 10 pL in volume were placed in Prometheus NT.48 NANODSF grade capillaries and the capillaries were loaded on the plate reader of the instrument. A discovery scan was then run to allocate samples and concentration identification. A size analysis was run using 5 acquisitions per replicate with each formulation having 3 replicates.

[0248] As presented in FIG. 3A, microemulsion particle formulations had significantly lower average particle sizes, which were no greater than 100 nm, as compared to OmniActive™ Lutemax 2020 formulations, which had particle sizes significantly greater than 100 nm.

[0249] Further, OmniActive™ Lutemax 2020 formulations did have some difference in particle sizes depending on the medium (z.e., water, Red Bull™, Monster™, Rockstar™) in which the OmniActive™ Lutemax 2020 formulation was included (for example, particle diameters of 300 nm + / - 40 nm for water and particle diameters of 200 nm + / - 25 nm for Red Bull™, Monster™, and Rockstar™). By contrast microemulsion particle formulations of the present disclosure had generally consistent particle sizes between each medium for each exemplary formulation. As can be seen, particle size was typically characteristic of a particular formulation, independent of the beverage with which it was mixed.

[0250] To determine if particle sizes changed during extended storage, microemulsion particle formulations and Omni Active™ Lutemax 2020 formulations were included and stored in each medium for a period of 30 days. Particle sizes were measured at the initial time of incorporation (z.e., day 0) of formulations in each medium and at day 30 and are presented in FIG. 4A, FIG. 5A, FIG. 6A, and FIG. 7A

[0251] As similarly observed in FIG. 3A, microemulsion particle formulations had significantly lower particle sizes as compared to OmniActive™ Lutemax 2020 formulations. Furthermore, microemulsion particle formulations were successful at maintaining particle sizes over the 30-day storage period in each medium (for example, under about 100 nm (or under about 60 nm) for all 30 days, as shown in FIG. 4A, FIG. 5A, FIG. 6A, and FIG. 7A). In contrast, Omni Active™ Lutemax 2020 formulations decreased in particle size over the 30-day storage period (for example, from about 300 nm to about 200 nm (FIG. 4A), from about 180 nm to about 170 nm (FIG. 5A), from about 170 nm to about 160 nm (FIG. 6A), and / or from about180 nm to about 160 nm (FIG. 7A). Without wishing to be bound by any particular theory, it is proposed that the OmniActive™ Lutemax 2020 particle formulations decrease in diameter over time due to particle diffusion and / or disintegration of the structure / composition. Thus, provided formulations may have certain advantages relative to certain other formulations, specifically including OmniActive™ Lutemax 2020, at least in that provided formulations may be more stable over time, particularly when incorporated into beverages.Example 3: Turbidity

[0252] The present example demonstrates that microemulsion particle formulations disclosed herein can be included in beverages (e.g., fortified beverages) such as, for example, water, energy drinks, etc. without negatively impacting one or more beverage properties, such as, for example, one or more visual properties, e.g., turbidity. Characteristics of beverages fortified with provided microemulsion particle formulations were compared to those of beverages which included other non-microemulsion particle formulations, for example Omni Active™ LuteMax 2020 beadlet particle formulation.

[0253] In the present example, turbidity was assessed using a Thermo Scientific Orion AQUAfast AQ3010 Turbidity Meter. Samples that were characterized included (i) water, (ii) Red Bull™, (iii) Monster™, and (iv) Rockstar™, each including (a) a microemulsion particle formulation, (b) an OmniActive™ Lutemax 2020 particle formulation (i.e., a non-microemulsion particle formulation), or (c) no added particle formulation (i.e., the control).

[0254] Prior to measuring turbidity, about 5mL of a sample was loaded into a clean and dry clear glass sample vial and tightly capped. The vial was inverted several times to coat the inside with sample and the sample was then discarded. The sample loading and inversion steps were repeated one additional time to ensure a uniform coating inside the vial. Next, each coated vial was filled with about 15 mL of the solution to be characterized and the vial was then capped. The sample vials were placed in the turbidity meter sample well and covered with a rubber cap. Turbidity was then measured and recorded according to the operating instructions of the turbidity meter. Particle sizes of each sample were also characterized, for example, as presented in Example 2.

[0255] As presented in FIG. 3B, microemulsion particle formulation beverages had significantly lower turbidity, no greater than 313 NTU, as compared to Omni Active™ Lutemax 2020 formulations, which had particle sizes significantly greater than 313 NTU. The lowerturbidity of fortified beverages which included microemulsion particle formulations correlated with the lower particle sizes that were observed with these formulations.

[0256] As shown in FIG. 8A, OmniActive™ Lutemax 2020 particle size varied between about 150 nm and 200 nm, as concentration increased while the exemplary microemulsion particle formulation demonstrated consistent particle size (diameter) of about 10 nm (or about 5 nm to about 15 nm) regardless of concentration. FIG. 8B - FIG. 8D show a comparison between a beverage including a microemulsion particle formulation (i.e., a fortified beverage including microemulsion particle formulation JL-D) and a beverage including an OmniActive™ Lutemax 2020 formulation (i.e., a non-microemulsion particle formulation) over a concentration range for each respective formulation that was included in the beverage. In FIG. 8B - FIG. 8D, Rockstar™ was the beverage in which each particle formulation was included. As seen in FIG. 8B and FIG. 8D, the exemplary microemulsion particle formulation showed minimal variation in turbidity (i.e., consistently below about 20 NTU) as the concentration of the microemulsion particle formulation increased. In contrast, the OmniActive™ Lutemax 2020 formulation showed a significant and roughly linear increase in turbidity (from about 50 NTU at 1 mg per 473 mL of Rockstar™ up to almost 1000 NTU (for example, 950 NTU) at 30 mg per 473 mL of Rockstar™) as the concentration of the Omni Active™ Lutemax 2020 formulation in beverage was increased. The increased turbidity of Omni Active™ Lutemax 2020 formulation beverages can be observed by eye, as seen in FIG. 8C, thus demonstrating that non-microemulsion particle formulations cause beverages to have unfavorable visual properties when included at high concentrations. FIG. 8A illustrates a plot of particle diameter size of microemulsion particle formulations and non-microemulsion particle formulations v. their concentration in a Rockstar™ energy drink, according to illustrative embodiments of the present disclosure.

[0257] Thus, microemulsion particle formulations of the present disclosure enable payload components to be mixed with beverages in large amounts without impacting the visual properties of the final product i.e., a fortified beverage). Including payload components at high amounts in beverages without a loss in the aesthetics of the final product allows for higher dosed payloads in fortified beverages while maintaining a product which has aesthetic qualities that an end-consumer is comfortable and / or familiar with consuming (e.g., reasonably comparable and / or substantially identical to those of a reference product). Further, higher dosed payloads in fortified beverages can provide for products which have more appropriately dosed payloads.

[0258] Additionally, particle formulations were included in beverages (z.e., water, Red Bull™, Monster™, and Rockstar™) and stored at room temperature for an extended period of 30 days. Microemulsion particle formulation fortified beverages were compared to OmniActive™ Lutemax 2020 formulation fortified beverages (z.c., non-microemulsion particle formulation fortified beverages) As observed in FIG. 4B - FIG. 4D, FIG. 5B - FIG. 5D, FIG. 6B - FIG. 6D, and FIG. 7B - FIG. 7D, microemulsion particle formulation fortified beverages had a significantly lower turbidity (for example, below about 320 NTU (FIG. 5B), or below about 200 NTU (FIG. 6B), or below about 220 NTU (FIG. 7B) in some cases) as compared to OmniActive™ Lutemax 2020 fortified beverages (above about 600 NTU (FIG. 4B), or in some cases, above about 580 NTU (FIG. 5B) at initial incorporation of the particle formulations into each beverage (z.e., at 0 days of storage). After 30 days of storage at room temperature, microemulsion particle formulation fortified beverages showed no significant changes and / or any changes in turbidity relative to 0 days of storage and maintained lower turbidity relative to OmniActive™ Lutemax 2020 formulation fortified beverages over the extended storage period.Example 4: Payload Stability

[0259] The present example demonstrates that microemulsion particle formulations as provided herein achieve stability of payload components in beverages over an extended period and, therefore, provide significant and desirable improvements over other (including, e.g., nonmi croemul si on) particle formulations, for example, OmniActive™ particles. In the present example, payload components in microemulsion particle formulations were lutein, vitamin D2, and vitamin Bl 2. Further, beverages that were fortified with microemulsion particle formulations were: water, Red Bull™, Monster™, Rockstar™, oatmilk (i.e., Oatly™ and oatmilk in the present example).

[0260] Lutein Recovery: To evaluate the stability that microemulsion particle formulations provide to lutein as a payload component the percent recovery was determined by quantifying the amount of lutein in a sample at a particular time interval. 9.9 mL of a beverage was added to a 12 mL glass vial and 100 pL of a microemulsion formulation was then added to the 12 mL glass vial. The vial was covered with a rubber stopper and aluminum seal, crimped shut, and vortexed to ensure proper mixing. The contents of the vial were measured for lutein recovery in replicates of three at time intervals of 0 days, 7 days, 14 days, 28 days, and 56 days. After each timepoint sample replicates were taken, sample vials were stored in a cardboardstorage box at 25 °C until the next timepoint was measured. To quantify lutein recovery, about 2 mL from each sample vial were transferred to a 2 mL Eppendorf tube and 500 pL aliquots for each sample were transferred into three (3) 2 mL Eppendorf tubes (i.e., 3 replicates, each containing 500 pL of sample). To each replicate, 500 pL of acetone was added and the respective Eppendorf tube was capped and vortexed for about 8-10 seconds. Then, to 500 pL of dichloromethane (DCM) was added to each Eppendorf tube containing a replicate, capped, and vortexed for about 8-10 seconds. All replicates were then added to a microcentrifuge and centrifuged for 5 minutes at 21,000 ref (max speed). After completing centrifugation, the beverage layer was visibly separated from the bottom solvent layer comprising acetone and DCM. The top beverage layer was the original color of the respective beverage being tested and the bottom solvent layer was yellow / orange in color. About 1 mL of the bottom solvent layer was transferred into a 2 mL glass HPLC vial and capped. Each replicate was then analyzed by HPLC to quantify the lutein in each sample by measuring the lutein peak area (mAU). HPLC parameters used are presented in TABLE 2. In cases where multiple lutein isomer peak were present, the sum of these peaks was used. The average lutein peak area of the 3 replicates was then measured and used for quantifying lutein recovery. The timepoint at 0 days was used as the basis for quantifying lutein recovery. Accordingly, lutein recovery was calculated as the percentage ratio of the average lutein peak area for each timepoint relative to the average lutein peak area at timepoint 0 days.TABLE 2. HPLC Parameters

[0261] As presented in FIG. 9A - FIG. 9H, microemulsion particle formulations comprising lutein were compared to OmniActive™ Lutemax 2020 particle formulations (i.e.,non-microemulsion particle formulations) for lutein stability performance characteristics (as quantified by lutein recovery) in Monster™ at a concentration of 5 mg lutein / 473 mL of Monster™. Microemulsion particle formulations showed superior stability performance characteristics as compared to OmniActive™ Lutemax 2020 particle formulations after two weeks of storage in Monster™.

[0262] As presented in FIG. 10A - FIG. 10D, microemulsion particle formulations comprising lutein were compared to Omni Active™ Lutemax 2020 particle formulations (i.e., non-microemulsion particle formulations) for lutein stability performance characteristics (as quantified by lutein recovery) in Rockstar™ at a concentration of 3 mg lutein / 473 mL of Rockstar™. Microemulsion particle formulations showed superior stability performance characteristics as compared to OmniActive™ Lutemax 2020 particle formulations after two weeks of storage in Rockstar™.

[0263] As presented in FIG. 11A - FIG. 11C, microemulsion particle formulations comprising lutein were characterized for lutein stability performance characteristics (as quantified by lutein recovery) in water at a concentration of 10 mg lutein / 10 mL of water. Microemulsion particle formulations showed desirable stability performance characteristics for a time period of up to 8 weeks storage in water.

[0264] As presented in FIG. 12A - FIG. 12C, microemulsion particle formulations comprising lutein were compared to OmniActive™ Lutemax 2020 particle formulations (i.e., non-microemulsion particle formulations) for lutein stability performance characteristics (as quantified by lutein recovery) in water (FIG. 12A), oatmilk (FIG. 12B), and Oatly™ beverage (FIG. 12C) at a concentration of 1 mg lutein / 100 mL of each respective beverage. Particle formulations mixed with water were stored at room temperature, while particle formulations mixed with oatmilk and Oatly™ beverage were stored at refrigerated temperatures (about 4 °C). Microemulsion particle formulations showed desirable stability performance characteristics for a time period of up to 2 weeks storage in water, oatmilk, and Oatly™ beverage.

[0265] Vitamin D2 Recovery. To evaluate the stability that microemulsion particle formulations provide to vitamin D2 as a payload component, 9.9 mL of a beverage was added to a 12 mL glass vial. 100 pL of a microemulsion formulation was then added to the 12 mL glass vial. The vial was covered with a rubber stopper and aluminum seal, crimped shut, and vortexed to ensure proper mixing. The contents of the vial were measured for vitamin D2 recovery inreplicates of three at intervals of 0 days, 7 days, 14 days, 28 days, and 56 days. After each timepoint sample replicates were taken, sample vials were stored in a cardboard storage box at 25 °C until the next timepoint was measured. To quantify vitamin D2 recovery, about 2 mL from each sample vial were transferred to a 2 mL Eppendorf tube and 500 pL aliquots for each sample were transferred into three (3) 2 mL Eppendorf tubes (i.e., 3 replicates, each containing 500 pL of sample). To each replicate, 500 pL of ethanol was added and the respective Eppendorf tube was capped and vortexed for about 8-10 seconds. Then, to 500 pL of hexane was added to each Eppendorf tube containing a replicate, capped, and vortexed for about 8-10 seconds. All replicates were then added to a microcentrifuge and centrifuged for 5 minutes at 21,000 ref (max speed). After completing centrifugation, the beverage layer was visibly separated from the bottom beverage layer and the top solvent layer. About 0.54 mL of the top solvent layer was transferred into a 2 mL glass HPLC vial and capped. Each replicate was then analyzed by HPLC to quantify the vitamin D2 in each sample by measuring the vitamin D peak area (mAU). HPLC parameters used are presented in TABLE 3. The average vitamin D peak area of the 3 replicates was then measured and used for quantifying vitamin D2 recovery. The timepoint at 0 days was used as the basis for quantifying vitamin D2 recovery. Accordingly, vitamin D2 recovery was calculated as the percentage ratio of the average vitamin D2 peak area for each timepoint relative to the average vitamin D2 peak area at timepoint 0 days.TABLE 3. HPLC Parameters

[0266] As presented in FIG. 13A - FIG. 13B, microemulsion particle formulations comprising vitamin D2 were assessed for vitamin D2 stability performance characteristics (as quantified by vitamin D2 recovery) and in water (FIG. 13A) and oatmilk (FIG. 13B) at aconcentration of 1 .3 mg vitamin D2 / 100 mL of respective beverage. For purposes of comparison with microemulsion particle formulations, performance characteristics were similarly assessed in a competitor product, exemplified by Provitas® D2-100SD formulation. Particle formulations mixed with water were stored at room temperature, while particle formulations mixed with oatmilk were stored at refrigerated temperatures (about 4 °C). Microemulsion particle formulations showed desirable stability performance characteristics for a time period of up to 2 weeks storage in water, oatmilk.

[0267] Vitamin Bl 2 Recovery : To evaluate the stability that microemulsion particle formulations provide to vitamin B 12 as a payload component, 9.9 mL of a beverage was added to a 12 mL glass vial. 100 pL of a microemulsion formulation was then added to the 12 mL glass vial. The vial was covered with a rubber stopper and aluminum seal, crimped shut, and vortexed to ensure proper mixing. The contents of the vial were measured for vitamin B12 recovery in replicates of three at intervals of 0 days, 7 days, 14 days, 28 days, and 56 days. After each timepoint sample replicates were taken, sample vials were stored in a cardboard storage box at 25 °C until the next timepoint was measured. To quantify vitamin B 12 recovery, about 2 mL from each sample vial were transferred to a 2 mL Eppendorf tube and 500 pL aliquots for each sample were transferred into three (3) 2 mL Eppendorf tubes (z.e., 3 replicates, each containing 500 pL of sample). To each replicate, 500 pL of ethanol was added and the respective Eppendorf tube was capped and vortexed for about 8-10 seconds. Then, to 500 pL of hexane was added to each Eppendorf tube containing a replicate, capped, and vortexed for about 8-10 seconds. All replicates were then added to a microcentrifuge and centrifuged for 5 minutes at 21,000 ref (max speed). After completing centrifugation, the beverage layer was visibly separated from the top solvent layer and the bottom beverage layer. About 0.5 mL of the bottom beverage layer was transferred into a 2 mL glass HPLC vial and capped. Each replicate was then analyzed by HPLC to quantify the vitamin B12 in each sample by measuring the vitamin B 12 peak area (mAU). HPLC parameters used are presented in TABLE 4. The timepoint at 0 days was used as the basis for quantifying vitamin B12 recovery. Accordingly, vitamin B 12 recovery was calculated as the percentage ratio of the average vitamin B 12 peak area for each timepoint relative to the average vitamin B12 peak area at timepoint 0 days.TABLE 4. HPLC Parameters

[0268] As presented in FIG. 14A - FIG. 14C, microemulsion particle formulations comprising vitamin B12 were characterized for vitamin B12 stability performance characteristics (as quantified by vitamin B12 recovery) in water (FIG. 14A), oatmilk (FIG. 14B), and Oatly™ beverage (FIG. 14C) at a concentration of 0.2 mg vitamin B12 / 100 mL of respective beverage. For purposes of comparison with microemulsion particle formulations, performance characteristics were similarly assessed in a competitor product, exemplified by DSM™ Vitamin B12 1% SD or Caldic™ 98% cyanocoblamin formulations. Particle formulations mixed with water were stored at room temperature, while particle formulations mixed with Oat milk and Oatly oat milk were stored at refrigerated temperatures (about 4 °C). Microemulsion particle formulations showed desirable stability performance characteristics for a time period of up to 2 weeks storage in water, Oat milk, and Oatly oat milk.Example 5: Delayed payload release

[0269] The present example demonstrates that exemplary microemulsion formulations as provided herein facilitate delayed release of payload components (e.g., caffeine) into solution.

[0270] Delayed release of caffeine has been a goal for the energy drink and carbonated beverage industries, among other things to reduce or avoid a caffeine “crash”. Those skilled in the art are aware that certain phenolic acids, specifically including those that include one or more gallic acid moieties, can bind to caffeine. Indeed, ability of phenols, polyphenols, and other agents (e.g., cyclodextrins) to complex with caffeine has been studies for decades (see, for example, Cai et al., J. Chem. Soc., Perkin Trans. 2:2197, 1990). Certain reports have described efforts to develop tannic-acid-based delayed-release caffeine preparations for inclusion in beverages, either as colloid preparations (see, for example, WO2022 / 266441) or as “emulsion” preparations (see, for example, WO2022 / 266442). The present disclosure identifies the source of various problems with such studies and, moreover, provides microemulsion particle formulations, beverages containing them, and technologies for production and use of both, that achieve results not reported for other proposed extended-release caffeine formulations, including those described in WO2022 / 266441 and / or WO2022 / 266442. Exemplary microemulsion formulations comprising caffeine were prepared according to methods disclosed herein. In the present example, microemulsion formulations comprising caffeine were prepared by a self- emulsification method. Caffeine and tannic acid were separately weighed and separately dissolved in water and heated at 70 °C. After full dissolution of each of caffeine and tannic acid, the caffeine solution was added rapidly into the tannic acid solution to form a solution having a milky color, which is indicative of a tannic acid - caffeine complex forming. Separately, a polysaccharide solution was also prepared by mixing a polysaccharide (e.g., xantham gum) in water. This polysaccharide solution was then mixed fully with the caffeine-tannic acid complex solution, forming an aqueous phase. Separately, a mixture of an oil component (e.g., soybean oil) and a surfactant component (e.g., polysorbate 80) was prepared in a vial. This resulting mixture was well mixed and heated at 70°C for at least 30 min, forming an oil phase. Next, the oil phase was mixed with the aqueous phase at a ratio of oil phase to aqueous phase of about 1 :4 v / v by adding the aqueous phase into the oil phase in a dropwise manner while being stirred. The mixture of oil phase and aqueous phase was stirred for at least 60 min to form a homogeneous suspension. Depending on the amount and type of oils and polysaccharides, themicroemulsion particles are formed in a size range of 10-200 nm in diameter in monodispersed manner i.e., formulations were characterized as having low PDI). Microemulsion particle formulation compositions of the present example are presented in TABLE 5.TABLE 5. Exemplary Compositions Comprising Caffeine

[0271] Caffeine Release '. To evaluate the release of caffeine from exemplary microemulsion formulations of the present disclosure, 1 mL of exemplary microemulsion formulation was added to a 50KD dialysis membrane in a Float-A-Lyzer dialysis device (Repligen™) and placed in 100 mL of water and simulated gastric fluid (SGF) mixture at a 1 : 1 ratio. Samples were collected after 2 hours, 4 hours, and 24 hours, and measured for the amount of caffeine that diffused out of the dialysis membrane. To quantify caffeine recovery, about 2 mL from each sample vial were transferred to a 2 mL Eppendorf™ tube and 500 pL aliquots for each sample were transferred into three (3) 2 mL Eppendorf™ tubes (i.e., 3 replicates, each containing 500 pL of sample). To each replicate, 500 pL of DCM was added and the respective Eppendorf™ tube was capped and vortexed for about 8-10 seconds. All replicates were then added to a microcentrifuge and centrifuged for 5 minutes at 21,000 ref (max speed). After completing centrifugation, the top beverage layer (i.e., aqueous phase) was visibly separated from the bottom solvent layer (i.e., organic phase) comprising DCM. About 0.5 mL of the bottom solvent layer was transferred into a 2 mL glass HPLC vial and capped. Each replicate was then analyzed by HPLC to quantify the caffeine in each sample by measuring the caffeinepeak area (mAU). HPLC parameters used are presented in TABLE 6. The average caffeine peak area of the 3 replicates was then measured and used for quantifying caffeine recovery. The timepoint at 0 days was used as the basis for quantifying caffeine recovery. Accordingly, caffeine recovery was calculated as the percentage ratio of the average caffeine peak area for each timepoint relative to the average caffeine peak area at timepoint 0 days.TABLE 6: HPLC Parameters

[0272] As shown in FIG. 15A - FIG. 15C, exemplary microemulsion formulations of the present disclosure delayed caffeine release into solution as compared to the free diffusion of un-formulated caffeine in solution. For example, while 100% of caffeine is released after 2 hours for un-formulated caffeine in solution, the JLC6 formulation released about 52% and 72% of the caffeine after 2 and 4 hours respectively, and the JLC6 formulation with 50KD in SGF / DI water in a 100:1 ratio released about 38% and 55% of the caffeine after 2 and 4 hours respectively (as shown in FIG 15A). These data indicate that exemplary microemulsion formulations of the present disclosure can delay payload component release to achieve sustained payload component bioavailability following ingestion of the formulation by a subject.

[0273] Caffeine Release After Storage'. To evaluate the release of caffeine from exemplary microemulsion formulations of the present disclosure after storage, exemplary microemulsion formulations of the present disclosure were added to sample beverages (e.g., Monster™ Energy Original energy drink, Pepsi soft drink, or Coca-Cola soft drink) at ratios of 1 : 1 or 1:100 (microemulsion formulation : beverage) and stored at room temperature for 3, 4, or 6 weeks with exposure to light. After storage, 1 mL of stored exemplary microemulsionformulation and sample beverage mixture was added to a 50KD dialysis membrane in a Float-A- Lyzer dialysis device (Repligen™) and placed in 100 mL water and simulated gastric fluid mixture at a 1 : 1 ratio. Samples were collected after 2 hours, 4 hours, and 24 hours, and measured for the amount of caffeine that diffused out of the dialysis membrane. To quantify caffeine recovery, about 2 mL from each sample vial were transferred to a 2 mL Eppendorf™ tube and 500 pL aliquots for each sample were transferred into three (3) 2 mL Eppendorf™ tubes (i.e., 3 replicates, each containing 500 pL of sample). To each replicate, 500 pL of DCM was added and the respective Eppendorf™ tube was capped and vortexed for about 8-10 seconds. All replicates were then added to a microcentrifuge and centrifuged for 5 minutes at 21,000 ref (max speed). After completing centrifugation, the top beverage layer (i.e., aqueous phase) was visibly separated from the bottom solvent layer (i.e., organic phase) comprising DCM. About 0.5 mL of the bottom solvent layer was transferred into a 2 mL glass HPLC vial and capped. Each replicate was then analyzed by HPLC to quantify the caffeine in each sample by measuring the caffeine peak area (mAU). HPLC parameters used are presented in TABLE 6. The average caffeine peak area of the 3 replicates was then measured and used for quantifying caffeine recovery. The timepoint at 0 days was used as the basis for quantifying caffeine recovery after the storage for 3 weeks, 4 weeks, or 6 weeks in sample beverage. Accordingly, caffeine recovery was calculated as the percentage ratio of the average caffeine peak area for each timepoint relative to the average caffeine peak area at timepoint 0 days.

[0274] As shown in FIG. 16A - FIG. 16B, exemplary microemulsion formulations (JLC6, JLC25, JLC28, and JLC29) of the present disclosure stored in Monster™ energy drink at a ratio of 1 ml microemulsion formulation to 1 ml of Monster™ energy drink for 4 weeks delayed caffeine release into solution as compared to the free diffusion of un-formulated caffeine in solution. For example, while about 85% and about 90% of the caffeine is released after 2 hours and 4 hours, respectively, for the un-formulated caffeine in solution, the JLC6 formulation released about 55% and 75% of the caffeine after 2 and 4 hours, respectively, and the JLC25 formulation released about 40% and 67% of the caffeine after 2 and 4 hours, respectively (as shown in FIG. 16A and FIG. 16B). These data indicate that exemplary microemulsion formulations of the present disclosure stored in Monster™ energy drink can delay payload component release to achieve sustained payload component bioavailability following ingestion of the formulation by a subject.

[0275] As shown in FIG. 17A - FIG. 17B, exemplary microemulsion formulations (JLC6, JLC25, JLC28, and JLC29) of the present disclosure stored in Pepsi soft drink at a ratio of 1ml of microemulsion formulation to 1ml of Pepsi soft drink for 6 weeks at room temperature delayed caffeine release into solution as compared to the free diffusion of un-formulated caffeine in solution. For example, while about 85% and about 90% of the caffeine was released after 2 hours and 4 hours, respectively, for the un-formulated caffeine in solution, the JLC6 formulation released about 60% and 80% of the caffeine after 2 and 4 hours, respectively, and the JLC29 formulation released about 40% and 65% of the caffeine after 2 and 4 hours, respectively (as shown in FIG. 17A and FIG. 17B). These data indicate that exemplary microemulsion formulations of the present disclosure stored in Pepsi soft drink can delay payload component release to achieve sustained payload component bioavailability following ingestion of the formulation by a subject.

[0276] As shown in FIG. 18A - FIG. 18B, exemplary microemulsion formulations (JLC25 and JLC28) of the present disclosure stored in Coca-Cola soft drink at a ratio of 1 ml microemulsion formulation to 99 ml of Coca-Cola soft drink for 3 weeks at room temperature delayed caffeine release into solution as compared to the free diffusion of un-formulated caffeine in solution. For example, while about 80% and about 87% of caffeine is released after 2 hours and 4 hours, respectively, for the un-formulated caffeine in solution, the JLC25 formulation released about 70% and 80% of the caffeine after 2 and 4 hours, respectively, and the JLC28 formulation released about 65% and 75% of the caffeine after 2 and 4 hours, respectively (as shown in FIG. 18A and FIG. 18B). These data indicate that exemplary microemulsion formulations of the present disclosure stored in Coca-Cola soft drink can delay payload component release to achieve sustained payload component bioavailability following ingestion of the formulation by a subject.

[0277] As shown in FIG. 19A - FIG. 19B, exemplary microemulsion formulations (JLC25, JLC27, JLC28, and JLC29) of the present disclosure stored in in Monster™ energy drink at a ratio of 1 ml microemulsion formulation to 99 ml of Monster™ energy drink for 4 weeks at room temperature delayed caffeine release into solution as compared to the free diffusion of un-formulated caffeine in solution. For example, while about 90% and about 95% of the caffeine is released after 2 hours and 4 hours, respectively, for un-formulated caffeine in solution, the JLC25 formulation released about 60% and about 82% of the caffeine after 2 and 4hours, respectively (as shown in FIG. 19A and FIG. 19B). These data indicate that exemplary microemulsion formulations of the present disclosure stored in Monster™ energy drink can delay payload component release to achieve sustained payload component bioavailability following ingestion of the formulation by a subject.

[0278] As shown in the present example, microemulsion formulations of the present disclosure maintain delayed release of highly water-soluble payload components (e.g., caffeine) even after long term storage in various aqueous beverages (specifically in various energy drinks and sodas).

[0279] Without wishing to be bound by any particular theory, the present disclosure proposes that one or more features of provided microemulsion particle formulations may contribute to their surprising and desirable properties, including relative to other reported caffeine formulations that are described as “extended release”.

[0280] To give but one example, the present disclosure notes that, in some embodiments, it may be desirable to utilize a molar ratio of caffeine to tannic acid that is greater than about 2: 1 or 3: 1 and in fact in some embodiments is in the range of 5: 1. Noting that tannic acid includes 5 gallic acid moieties (conjugated to a sugar), the present disclosure appreciates that a molar ratio of about 5 caffeine: 1 tannic acid may substantially saturate caffeine binding sites on the tannic acid. The present disclosure notes that WO2022 / 266442 explicitly studies characteristics of certain caffeine:tannic acid complexes with molar ratios such as about 9: 1, about 6: 1, about 4: 1 and about 3: 1, and selects the lowest of these (about 3: 1, which corresponds to a weight percent ratio of about 1 :3 caffeine Tannic acid) for inclusion in emulsion formulations. Furthermore, all preparation of caffeine:tannic acid complexes exemplified in WO2022 / 266442 generate solidform (e.g., powder) caffeine Tannic acid complexes. Indeed, explicit steps (e.g., precipitation, centrifugation, and / or spray-drying) are taught to achieve preparation of solid caffeineTannic acid complexes; these solid (e.g., dried) caffeineTannic acid complexes were then ground and sieved to generate a powder that was then combined with an oil phase (and other components) to generate a composition described as an “emulsion”. These emulsions were assessed for their stability (in terms of caffeine release over time) in certain aqueous solutions and the percentage of encapsulated (or free) caffeine was described as “remain[ing] stable” when in fact, for many formulations, percentage of encapsulated vs free caffeine changed dramatically over time, oscillating both up and down, sometimes by as much as two-fold or more. Those skilled in theart appreciate that changes of such magnitude would represent unacceptably unreliable, and potentially dangerous shifts, in ingestible caffeine levels in beverages. Furthermore, reported “extended release” profiles from exemplified emulsion compositions extended over many days to weeks. Still further, a highlighted hallmark of the described compositions was that substantially complete release was triggered by exposure to pH corresponding to that encountered in the small intestine. No exemplification of stability or release characteristics was provided for any emulsion that had been combined with and stored in a beverage for any significant length of time. Indeed, no beverage composition that had included a described emulsion composition for any such length of time was exemplified.

[0281] The present Example notes that various features of extended-release caffeine compositions (i.e., microemulsion particle formulations and / or fortified beverages that contain them) exemplified herein (and / or in other Examples) distinguish them from those exemplified in WO2022 / 266442. Without wishing to be bound by any particular theory, the present example proposes, for example, that one or more of form of caffeine: tannic acid complexes, relative amounts of caffeine and tannic acid (and / or other caffeine-binding entities), relative amounts of one or more other components (e.g., oil, surfactant, etc.) may contribute to these different features.

[0282] Furthermore, the present Example notes that, those skilled in the art, once provided with teachings of the present disclosure, including provided documentation of features described herein (e.g., release characteristics and / or their stability over time in beverages, including, in some embodiments, in multiple different beverages) will appreciate that various adjustments to identity and / or relative amounts of specific components are permitted within the scope of the present disclosure, and will be able to generate and characterize a range of particular compositions as taught herein, characterized by one or more features and / or properties reasonably comparable to those documented herein (among other things, in light of provided description of exemplary useful formulations and / or beverages which then, among other things, can be comparators).Example 6: Diffusion-mediated release

[0283] The present example demonstrates that exemplary microemulsion formulations as provided herein facilitate delayed release of payload components (e.g., caffeine) into solution as a function of diffusion.

[0284] Exemplary microemulsion formulations comprising caffeine are prepared according to methods disclosed herein. In the present example, microemulsion formulations comprising caffeine are prepared by a self-emulsification method. See Example 5 for exemplary preparation methods.

[0285] Caffeine Release '. To evaluate the release of caffeine via diffusion from exemplary microemulsion formulations of the present disclosure, 1 mL of exemplary microemulsion formulation is added to a 50KD dialysis membrane in a Float-A-Lyzer dialysis device (Repligen™) and placed in 100 mL of water and simulated gastric fluid (SGF) mixture at a 1 : 1 ratio with varying amounts of free caffeine in either the dialysis device or the water / SGF mixture. Concentration of free caffeine in either compartment (in the dialysis device or in the water / SGF mixture) ranges from 0.025-0.32 mg / ml caffeine; this concentration range mimics the minimum and maximum caffeine contents after ingestion of a caffeinated beverage (e.g., soda, energy drink) and integration with stomach fluids. As such, this range represents the liquid environmental conditions at which microemulsion particles containing caffeine would enable sustained / extended release.

[0286] Samples are collected after 0, 5, 15, 30, 45 minutes and / or 1, 2, 3, 4, 5, 24 hours, and measured for the amount of caffeine that diffused out of the dialysis membrane. In this case, different free caffeine concentrations, either inside or outside of the dialysis device are used to create various caffeine concentration gradients (in relation to the caffeine loaded microemulsions) to evaluate how the environmental caffeine concentration influences diffusion (e.g., rate, amount of caffeine, etc.) of caffeine from inside the microemulsion and into the environment. See Example 5 for exemplary analytical methods.

[0287] Exemplary microemulsion formulations of the present disclosure delay caffeine release into solution as a function of environmental (e.g., in the liquid phase inside the dialysis device but outside of the microemulsions, in the liquid phase outside of the dialysis device and outside the microemulsions, etc.) caffeine and / or as a function of the caffeine concentration gradient. Exemplary microemulsion formulations of the present disclosure can delay payload component release to achieve sustained payload component bioavailability following ingestion of the formulation by a subject, as mediated by diffusion or caffeine concentration gradients. Exemplary microemulsions can enable the same diffusion-mediated or caffeine concentrationgradient mediated release of caffeine after storage in various beverages (e.g., Monster™, Coca- Cola™, Pepsi™, Rockstar™, etc.) for up to 2 years at room temperature.Example 7: Maintaining consistent concentrations of microemulsion encapsulated caffeine during shelf-storage

[0288] The present example teaches that exemplary microemulsion formulations as provided herein enable consistent caffeine encapsulation (e.g., minimal diffusion of caffeine between the microemulsion encapsulated caffeine and free caffeine contained in a beverage with which the microemulsion is combined) within microemulsions in beverages during shelf-storage.

[0289] Exemplary microemulsion formulations comprising caffeine are prepared according to methods disclosed herein. In the present example, microemulsion formulations comprising caffeine are prepared by a self-emulsification method. See Example 5 for exemplary preparation methods.

[0290] Caffeine Encapsulation. To evaluate the encapsulation of caffeine within beverages from exemplary microemulsion formulations of the present disclosure, 0.5 mL of exemplary microemulsion formulation mixed with a beverage (e.g., Monster Energy, Coca-Cola, Pepsi, Rockstar, etc.) are added to a vivaspin 5kDa spin column and centrifuged at 7,000 RCF. The spin column enables separation of the caffeine-containing microemulsions from both the free caffeine contained within the beverage and the beverage (e.g., Monster Energy, Coca-Cola, Pepsi, Rockstar, etc.). This process enables quantification of the caffeine content that resides within the microemulsions and furthermore enables quantification of the changes to caffeine concentrations in the beverage and in the microemulsions over various periods of time (e.g., to investigate diffusion of caffeine between microemulsions and environment).

[0291] Samples are collected after 0, 1, 2, 4, 8, 12, 24, 48, 96 weeks and measured for the amount of caffeine in the liquid beverage and also the amount of caffeine that remained within the microemulsions. In this case, the 0 timepoint serves as the baseline control to define starting caffeine in the beverage and starting caffeine in the microemulsions. Using the 0 timepoint as the baseline control enables time-dependent analysis of caffeine diffusion (e.g., transport, migration) between the microemulsions and the beverages. See Example 5 for exemplary analytical methods.

[0292] Exemplary microemulsion formulations of the present disclosure maintain a constant concentration of caffeine within the microemulsions; importantly, caffeine migration or diffusion from the beverage and into the microemulsions does not occur in a significant amount. This indicates high stability of the microemulsions and furthermore the ability of the microemulsions to maintain equilibrium of caffeine concentrations when in the presence of caffeinated beverages for long periods of time. Exemplary microemulsion formulations of the present disclosure can prevent payload component release to achieve sustained payload component bioavailability following ingestion of the formulation by a subject. Exemplary microemulsion can enable maintenance of constant caffeine concentrations in the beverage and within the microemulsions after storage in various beverages (e.g., Monster, Coca-Cola, Pepsi, Rockstar, etc.) for up to 2 years at room temperature.Example 8: Delayed caffeine release is independent of environmental pH

[0293] The present example teaches that exemplary microemulsion formulations as provided herein facilitate delayed release of payload components (e.g., caffeine) into solution, independent of solution pH. Among the advantages provided by such technologies is the feature that a pH-independent release mechanism (e.g., diffusion, concentration gradient, etc.) can enable integration of sustained / extended / controlled release technologies into liquid products of any pH (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10). Thus, certain provided microemulsion particle formulations are characterized in that they achieve delayed release (e.g., relative to free payload and / or to payload not incorporated in a provided microemulsion formulations) of a payload component incorporated within them at any of a variety of pHs.

[0294] Exemplary microemulsion formulations comprising caffeine are prepared according to methods disclosed herein. In the present example, microemulsion formulations comprising caffeine are prepared by a self-emulsification method. See Example 5 for exemplary preparation methods.

[0295] Caffeine Release '. The release of caffeine via diffusion from exemplary microemulsion formulations of the present disclosure after storage in a beverage (e.g., energy drink, soda, water, juice) is evaluated at pH values ranging from 2-10. In some cases, the pH of the beverage is adjusted using HC1 or NaOH as needed. After storage for a specific time period (e.g., 0 days to 2 years), 1 mL of exemplary microemulsion formulation in a beverage is added to a 50KD dialysis membrane in a Float-A-T vzsr dial qiq 4 A vice (Repligen™) and placed in 100mL of water and simulated gastric fluid (SGF) mixture at a 1 : 1 ratio with varying amounts of free caffeine in either the dialysis device or the water / SGF mixture, and / or in 100 mL of water and simulated intestinal fluid (SIF) mixture at a 1 : 1 ratio with varying amounts of free caffeine in either the dialysis device or the water / SIF mixture. By evaluating both SGF-based (acidic pH) and SIF-based (neutral pH) media, pH-independent release of caffeine from microemulsions after storage in a beverage (which may also have different pH values) can be determined.Concentration of free caffeine in either compartment (in the dialysis device or in the water / SIF or water / SGF mixture) ranges from 0.025-0.32 mg / ml caffeine; this concentration range mimics the minimum and maximum caffeine contents after ingestion of a caffeinated beverage (e.g., soda, energy drink) and integration with stomach / intestinal fluids. As such, this range represents the liquid environmental conditions at which microemulsion particles containing caffeine would enable sustained / extended release.

[0296] After storage in the beverage and addition to the dialysis device and exposure to the water / SIF or water / SGF fluids, samples are collected after 0, 5, 15, 30, 45 minutes and / or 1, 2, 3, 4, 5, 24 hours, and measured for the amount of caffeine that diffused out of the dialysis membrane. In this case, beverages at various pH values (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10) and water / SIF and / or water / SGF solutions at various pH values are used to investigate both: (A) how the shelf-storage of the microemulsions in the same beverages at various pH values affects the subsequent release of caffeine in physiological fluids, and (B) how exposure to fluids at 2 relevant physiological pH values (mimicking stomach and intestines) after beverage storage influences caffeine release.

[0297] Exemplary microemulsion formulations of the present disclosure delay caffeine release into solution as a function of environmental caffeine concentration and / or caffeine concentration gradient, and not as a function of environmental pH. As in Example 6, various environmental caffeine concentrations are also used to demonstrate caffeine concentration gradient-dependent release. Exemplary microemulsion formulations of the present disclosure can delay payload component release to achieve sustained payload component bioavailability following ingestion of the formulation by a subject, as mediated by diffusion or caffeine concentration gradients; this can be demonstrated after storage in beverages at various acidic,neutral, and basic pH values and also demonstrated after exposure to various physiological pH values mimicking the stomach and intestines.

[0298] Certain embodiments of the present disclosure have been described above. It is, however, expressly noted that the present disclosure is not limited to those embodiments, but rather the intention is that additions and modifications to what was expressly described in the present disclosure are also included within the scope of the disclosure. Moreover, it is to be understood that the features of the various embodiments described in the present disclosure were not mutually exclusive and can exist in various combinations and permutations, even if such combinations or permutations were not made express, without departing from the spirit and scope of the disclosure. The disclosure has been described in detail with particular reference to certain embodiments thereof, but it will be understood that variations and modifications can be effected within the spirit and scope of the claimed invention.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A microemulsion particle composition comprising: an oily phase comprising fatty acid particles that are dispersed within an aqueous liquid phase, wherein the oily phase further comprises a payload component, a surfactant component and, optionally one or both of an antioxidant component and a stabilizing component, and wherein the payload component is or comprises caffeine and a complexing agent, in a molar ratio greater than 3 : 1 caffeine:complexing agent.

2. The microemulsion particle composition of claim 1, wherein the complexing agent is tannic acid, a catechin, epigallocatechin-3 -gallate, gallic acid or a derivative thereof, or an alagi tannin.

3. The microemulsion particle composition of claim 1 or 2, wherein the complexing agent is tannic acid.

4. The microemulsion particle composition of any one of claims 1 to 3, characterized by an average particle size or particle size distribution such that combination of the microemulsion particle composition with a base beverage does not materially change turbidity of the base beverage.

5. The microemulsion particle composition of any one of claims 1 to 4, characterized in that its average particle size or particle size distribution remains stable upon combination with a base beverage.

6. The microemulsion particle composition of claim 5, wherein the average particle size or particle size distribution remains stable throughout storage for a period of time at least eight (8) weeks long after combination with a base beverage.

7. The microemulsion particle composition of any one of claims 1 to 6, the microemulsion particle composition being characterized in that one or more of: its average particle size, its particle size distribution, and its payload release characteristics, remains reasonably stable throughout storage for a period of time at least eight (8) weeks long after combination with a base beverage.

8. A formulation comprising one or more microemulsion particles and at least 79 wt% water, wherein the one or more microemulsion particles comprises:0.01 wt% to 0.13 wt% of a payload component;0.1 wt% to 2 wt% of a fatty component;12 wt% to 20 wt% of a surfactant component;0.1 wt% to 2 wt% of an antioxidant component; and0.1 wt% to 4 wt% of a stabilizing component.

9. The formulation of claim 8, wherein the payload component comprises lutein, caffeine, vitamin D2, zeaxanthin, vitamin Bl 2, or combination thereof.

10. The formulation of claim 8 or 9, wherein the fatty component comprises soybean oil, corn oil, safflower oil, olive oil, stearine, beeswax, canola oil, mineral oil, sunflower oil, glyceryl tripalmitate, medium chain triglycerides, coconut oil, or combination thereof.

11. The formulation of any one of claims 8 to 10, wherein the surfactant component comprises polysorbate 80, polysorbate 60, saponin, coco glucoside, 12-hydroxy stearic acid, palmitic acid, stearic acid, polyvinylpyrrolidone, propylene glycol, or combination thereof.

12. The formulation of any one of claims 8 to 11, wherein the antioxidant component comprises a-tocopherol, rosemary oil, citric acid, glutathione, astaxanthin, butylated hydroxyanisole, butylated hydroxytoluene, or combination thereof.

13. The formulation of any one of claims 8 to 12, wherein the stabilizing component comprises buttermilk, stearyl alcohol, glycerol, lecithin, P-sitosterol, cholesterol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, tetradecanol, octadecanol, hexadecanol, carboxymethyl cellulose, sterol, stanol, cardiolipin, or combination thereof.

14. The formulation of any one of claims 8 to 13, wherein the one or more microemulsion particles comprise a diameter in a range from 5 nm to 150 nm, 10 nm to 125 nm, 20 nm to 100 nm, or 25 nm to 75 nm.

15. A fortified beverage comprising: the formulation of any one of claims 8 to 14; and a base beverage.

16. The fortified beverage of claim 15, wherein the base beverage comprises an energy drink, water, nutrient-fortified water, carbonated drink, coffee, tea, juice, milk, milk alternative, or baby formula.

17. The fortified beverage of claim 15 or 16, wherein the fortified beverage comprises 0.5 % w / v to 2 % w / v of the payload component.

18. The fortified beverage of any one of claims 15 to 17, wherein the fortified beverage is characterized by having a turbidity no greater than 600 NTU, no greater than 575 NTU, no greater than 550 NTU, no greater than 525 NTU, no greater than 500 NTU, no greater than 400 NTU, no greater than 300 NTU, no greater than 200 NTU, no greater than 100 NTU, or no greater than 50 NTU.

19. The fortified beverage of any one of claims 15 to 18, wherein the fortified beverage comprises the formulation at a concentration of 0.001 to 0.075 mg / ml, 0.01 to 0.075 mg / ml, 0.02mg / ml to 0.075 mg / ml, 0.04 mg / ml to 0.075 mg / ml, or 0.06 mg / ml to 0.075 mg / ml of energy drink.

20. The fortified beverage of any one of claims 15 to 19, wherein at least 80% of the payload component is recoverable from the fortified beverage after 8 weeks of storage.

21. The fortified beverage of any one of claims 15 to 20, wherein at least 75% of the payload component is recoverable from the beverage after 16 weeks of storage.

22. A fortified beverage composition comprising an aqueous liquid phase and a fatty particle phase, wherein: at least the particle phase comprises a payload component, wherein: the fortified beverage composition has been stored for a period of time that is at least about 8 weeks long; the payload component is present in the particle phase in an amount reasonably comparable to that at which it was present prior to such storage; and the fortified beverage composition is characterized in that, when it is contacted with simulated gastric fluid, the payload component is released into the simulated gastric fluid so that the payload component is released into the simulated gastric fluid over a period of up to 12 hours.

23. The fortified beverage of claim 22, wherein the period of time is about 8 weeks and the amount of payload component present in the particle phase is at least 80% of that present prior to such storage.

24. The fortified beverage of claim 22, wherein the period of time is about 16 weeks and the amount of payload component present in the particle phase is at least 75% of that present prior to such storage.

25. A fortified beverage composition comprising an aqueous liquid phase and a fatty particle phase, wherein:each of the aqueous liquid phase and the fatty particle phase includes caffeine and the total caffeine in the fortified beverage composition is within a range of 30 mg / L to 600 mg / L; at least 40% of the caffeine is present in the fatty particle phase; and the fortified beverage composition is characterized in that, when it is contacted with simulated gastric fluid, the payload component is released into the simulated gastric fluid so that the payload component is released into the simulated gastric fluid over a period of about 4 hours to about 6 hours.

26. The fortified beverage composition of claim 25, which fortified beverage composition has been stored for a period of time that is at least 8 weeks.

27. A method for fortifying a beverage, the method comprising: i) providing a microemulsion particle formulation; and ii) mixing the microemulsion particle formulation with the beverage to produce a fortified beverage, wherein the microemulsion particle formulation comprises one or more microemulsion particles and at least 79 wt% water, and the one or more microemulsion particles comprises:0.01 wt% to 0.13 wt% of a payload component;0.1 wt% to 2 wt% of a fatty component;12 wt% to 20 wt% of a surfactant component;0.1 wt% to 2 wt% of an antioxidant component; and0.1 wt% to 4 wt% of a stabilizing component.

28. The method of claim 27, wherein providing the microemulsion particle formulation comprises: i) preparing an aqueous phase; ii) preparing an oil phase; and iii) adding the aqueous phase to the oil phase to produce the one or more microemulsion particles.

29. The method of claim 28, wherein:i) preparing the aqueous phase comprises mixing water and the antioxidant component; and ii) preparing the oil phase comprises mixing the payload component, the oil component, the surfactant component, and the stabilizing component.

30. The method of claim 29, wherein the payload component comprises lutein, vitamin D, zeaxanthin, vitamin B 12, or a combination thereof.

31. The method of claim 29, wherein: i) preparing the aqueous phase comprises mixing water, the payload component, and the antioxidant component; and ii) preparing the oil phase comprises mixing the oil component, the surfactant component, and the stabilizing component.

32. The method of claim 31, wherein the payload component comprises caffeine.

33. A formulation comprising one or more microemulsion particles and at least 73 wt% water, wherein the one or more microemulsion particles comprises:2 wt% to 5 wt% of a payload component;2 wt% to 8 wt% tannic acid;0.1 wt% to 4 wt% of a fatty component;12 wt% to 16 wt% of a surfactant component;0.1 wt% to 2 wt% of an excipient component; and0.1 wt% to 2 wt% of a stabilizing component.

34. The formulation of claim 33, wherein the payload comprises caffeine, wherein the surfactant comprises polysorbate 80, and wherein the stabilizing component comprises xanthan gum.

35. The formulation of claim 33, wherein the excipient component comprises at least one of alginate, 210S, carrageenan, maltose, and pectin.

36. The formulation of claim 33, wherein the payload comprises caffeine, and wherein the formulation comprises the payload component and tannic acid in a combined weight percent in a range from 8 wt% to 9 wt%.

37. A formulation comprising one or more microemulsion particles and at least 67 wt% water, wherein the one or more microemulsion particles comprises:0.01 wt% to 0.15 wt% of a pay load component;2 wt% to 6 wt% of ethanol;2 wt% to 6 wt% of isoamyl acetate; and5 wt% to 12 wt% of Kolliphor EL.

38. The formulation of claim 37, wherein the payload comprises free vitamin B12 powder.

39. A method of evaluating payload release from a microemulsion formulation, the method comprising: adding a first mixture of the microemulsion, water and simulated gastric fluid (SGF) to a dialysis device; sampling the mixture after multiple periods of time; dividing each sample into multiple replicates, each replicate of the multiple replicates being disposed within a tube separate from tubes containing other replicates of the multiple replicates; adding dichloromethane (DCM) to each tube; capping each tube; vortexing each tube for a first predetermined period of time; centrifuging each tube for a second predetermined period of time at a predetermined rotational speed, thereby forming a top layer and a bottom layer of the mixture; separating the top layer from the bottom layer of each replicate of each sample; and performing high performance liquid chromatography (HPLC) of the bottom layer of each replicate of each sample to analyze release of the payload from each sample.

40. The method of claim 39, wherein the first predetermined period of time comprises 8-10 seconds; wherein the second predetermined period of time comprises 4-6 minutes; and wherein the rotational speed comprises a rotational speed in a range from about 20,000 ref to about 21,500 ref.

41. The method of claim 39, wherein performing high performance liquid chromatography (HPLC) comprises using a diode-array detector to measure UV absorbance at a wavelength in a range from about 250 nm to about 450 nm at a column temperature in a range from about 15 °C to about 45 °C.

42. The method of claim 39, wherein the payload comprises lutein, caffeine, vitamin D2 or vitamin Bl 2.

43. The method of claim 39, wherein the microemulsion comprises a microemulsion particle composition according to any one of claims 1 to 7.

44. A method for fortifying a beverage, the method comprising: i) providing a microemulsion particle formulation; and ii) mixing the microemulsion particle formulation with the beverage to produce a fortified beverage, wherein the microemulsion particle formulation comprises one or more microemulsion particles and at least 79 wt% water, and the one or more microemulsion particles comprises:0.01 wt% to 0.13 wt% of a payload component;0.1 wt% to 2 wt% of a fatty component;12 wt% to 20 wt% of a surfactant component;0.1 wt% to 2 wt% of an antioxidant component; and0.1 wt% to 4 wt% of a stabilizing component, and wherein the resulting fortified beverage composition is characterized in that, when it is contacted with simulated gastric fluid, the payload component is released into the simulatedgastric fluid so that the payload component is released into the simulated gastric fluid over a period of about 4 hours to about 12 hours.

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