FR3153263A1 - Improved manufacturing process for stable suspensive dispersions - Google Patents

Abstract

Improved Method for Manufacturing Stable Suspension Dispersions The present invention relates to a method for manufacturing a dispersion comprising drops of fatty phase suspended in a continuous aqueous phase, the method comprising at least the steps of: a. providing at least one fatty phase in liquid form in a first chamber, the fatty phase comprising at least one oil and optionally at least one lipophilic gelling agent; b. providing at least one aqueous phase in liquid form in a second chamber, the aqueous phase comprising water and at least one hydrophilic gelling agent; the first chamber and the second chamber being fluidically connected by one or more channels, preferably by microchannels; c. guiding the fatty phase of step a. from the first chamber through the channel(s) into the second chamber; and d. exposing the aqueous phase of the dispersion of step c. to at least one gelation inducer of the hydrophilic gelling agent, whereby a dispersion comprising drops of fatty phase suspended in the continuous aqueous phase is obtained. Figure for abstract: None

Description

Improved manufacturing process for stable suspensive dispersions

The invention relates to a method for manufacturing a stable dispersion comprising drops of at least one fatty phase suspended in a continuous aqueous phase.

To date, there are stable dispersions of drops, in particular macroscopic ones, of a fatty phase dispersed in a continuous aqueous phase, obtained using a microfluidic process as described in WO2022106361 or WO2023152031.

Such microfluidic processes are particularly effective in forming dispersions comprising drops of controlled size.

On the other hand, such microfluidic processes do not make it easy to obtain dispersions in which the drops are suspended in a continuous aqueous phase. Indeed, the constraints inherent in the processes described in WO2022106361 or WO2023152031 require the use of a non-viscous or low-viscous aqueous phase in order to ensure the proper formation of the drops. After collecting the dispersion, two options are possible to form a suspensive dispersion. First, in cases where the aqueous phase can be preserved, its viscosity is increased by the addition of a gelation inducer by means of a subsequent step which requires prior collection of the formed dispersion. Second, in cases where the aqueous phase cannot be preserved, the dispersion is subjected to subsequent steps of filtration, optionally washing, then redispersion in a new aqueous phase with the expected viscosity, and therefore suspensivity.

All these subsequent stages therefore require discontinuous manufacturing processes, which is a disadvantage, particularly when seeking to produce large volumes, and even more so on an industrial scale.

These options also have several other disadvantages, namely:

- the homogeneous distribution of the gelation inducer in the aqueous phase (1st option) and the filtration/washing/redispersion steps (2nd option) induce strong shears/stresses which can alter the integrity of the drops;

- it is often difficult, or even impossible, to obtain a completely homogeneous distribution of the gelling inducer in the aqueous phase (1st option); the viscosity and the suspensive power of the aqueous phase with respect to the drops is therefore not identical at all points, thus leading to inhomogeneous delivery of the dispersion and/or localized creaming of the drops; and

- these options are not or only slightly compatible when seeking to obtain a viscous continuous aqueous phase, for example greater than 5000 cP (centipoise).

Ultimately, methods such as described in WO2022106361 or WO2023152031 suffer from limited overall operational capability.

It is therefore a general aim to advance the state of the art relating to the manufacture of dispersions and to propose an improved alternative to the prior art described above.

In particular, the present invention aims to propose a microfluidic manufacturing method which, in particular compared to those described in WO2022106361 and WO2023152031, is simplified, easily industrializable and without risk to the integrity of the drops, while remaining satisfactory in terms of capacity for precise control of the size of the drops and optionally the thickness of their envelope.

Thus, the invention relates to a method for manufacturing a stable dispersion comprising drops of fatty phase suspended in a continuous aqueous phase, the method comprising at least the steps of:

a. providing in a first chamber at least one fatty phase in liquid form, the fatty phase comprising at least one oil and optionally at least one lipophilic gelling agent;

b. providing in a second chamber at least one aqueous phase in liquid form, the aqueous phase comprising water and at least one hydrophilic gelling agent;

the first chamber and the second chamber being fluidically connected by one or more channels, preferably by micro-channels;

c. guiding the fatty phase of step a. from the first chamber through the channel(s) into the second chamber; and

d. exposing the aqueous phase of the dispersion of step c. to at least one gelling inducer of the hydrophilic gelling agent, whereby a dispersion comprising drops of fatty phase suspended in the continuous aqueous phase is obtained.

The dispersion obtained at the end of step d. can be recovered in a container.

Preferably, step d. is carried out upstream of the container in which the dispersion is intended to be stored and/or packaged. This container may be, for example, a storage tank or final packaging, as described below.

The invention also relates to a composition, in particular a cosmetic composition, comprising at least one dispersion produced according to the process according to the invention, optionally in association with a physiologically acceptable medium.

Unless otherwise stated, in all that follows, we consider that we are at room temperature (for example T=25°C ± 2°C) and atmospheric pressure (760 mm Hg, or 1,013.10 ⁵ Pa or 10 ¹³ mbar).

In the context of the present invention, the aforementioned dispersions may be referred to interchangeably by the term “emulsions”.

By "stable" or "kinetic stability" is meant, for the purposes of the present invention, at room temperature and atmospheric pressure, a dispersion whose continuous aqueous phase is capable of suspending the drops of dispersed fatty phase for a period of time greater than or equal to 1 month, preferably greater than or equal to 3 months, better still greater than or equal to 6 months, and most particularly greater than or equal to 12 months. In addition, it is meant to denote a dispersion devoid of any phenomenon of creaming or sedimentation of the drops of dispersed fatty phase in the continuous aqueous phase, but also devoid of opacification of the aqueous phase, of aggregation of the drops with each other, and in particular of coalescence or Oswald ripening of the drops with each other, of adhesion of the drops to the packaging and of leakage of materials from the dispersed fatty phase to the continuous aqueous phase, or vice versa.

According to the invention, the pH of a dispersion is typically between 4.0 and 8.0, in particular between 5.0 and 7.0.

Preferably, a dispersion according to the invention does not comprise a surfactant.

Preferably, a dispersion, in particular the continuous aqueous phase, does not comprise a hydrophilic surfactant.

Preferably, a dispersion, in particular the dispersed fatty phase, does not comprise a lipophilic surfactant.

Preferably, a method according to the invention does not comprise a step of evaporation, or elimination, of solvent(s), in particular as described in WO2022179982.

It is understood that steps a. and b. do not necessarily have to be performed in this order. It may also be possible to perform step b. first, then step a., or to perform them simultaneously.

Step c. of the method according to the invention is advantageous in that it makes it possible to generate in the second chamber a dispersion in which each droplet comprises the fatty phase from step a. In step c., the aqueous phase has not yet been exposed to at least one gelation inducer of the hydrophilic gelling agent. In other words, in step c., the viscosity and suspensivity of the continuous aqueous phase are not yet increased. The dispersion of step c. can therefore be described as a non-suspensive dispersion. The dispersion of step c. can also be described as a "transient dispersion" or "non-suspensive transient dispersion". The use of the emulsification step c., i.e. guiding the fatty phase from step a. through the microchannels, makes it possible to precisely control the size and ensure a uniform distribution of the size of the fatty phase drops dispersed in the continuous aqueous phase. In addition, the process allows rapid drop production, in the order of 100 g/h or more, or even up to 500 g/h.

Step d. of the process according to the invention makes it possible to increase the viscosity and suspensivity of the continuous aqueous phase, whereby a stable and suspensive dispersion is obtained with respect to the drops of fatty phase. The dispersion formed in step d. can therefore be described as a “suspensive dispersion”, “final suspensive dispersion” or “final dispersion”.

According to a particular embodiment, it is understood that steps c. and d. can be executed simultaneously, in particular when step d. is carried out directly in the second chamber and/or when the method operates in a continuous regime, as described in more detail below.

In the context of the present invention, when the drops comprise an envelope, the term “drop” may be designated indifferently by the term “capsule”.

For the purposes of the present invention, the term “microchannel” means a channel having an internal diameter of less than 4 mm, preferably between 1 µm and 4 mm, and in particular between 10 µm and 1 mm.

The first chamber and the second chamber are typically separated from each other except for the channel, or channels, connecting the first chamber to the second chamber. A chamber as used herein is configured to be filled with at least one solution. Typically, the chambers are closed except for the inlets, channels and outlets. The first chamber typically comprises a first fluid inlet for introducing, in particular continuously, the fatty phase of step a. into the first chamber and the second chamber has a second inlet for introducing, in particular continuously, the aqueous phase of step b. into the second chamber. According to a particular embodiment, the second chamber may also have a third inlet for introducing, in particular continuously, the gelling inducer, in particular in the form of an additional solution as described below, into the second chamber. The second chamber also comprises an outlet for discharging, preferably continuously, the dispersion formed during step c., or even during step d. when the latter is carried out in whole or in part in the second chamber.

It is understood that the channel(s) each comprise an inlet opening into the first chamber and an outlet opening into the second chamber. Thus, the channel(s) are directly connected to the first chamber and to the second chamber. Typically, the first chamber and the second chamber are fluidically connected by several channels, for example at least 10, at least 20, at least 30, at least 50 or at least 100 channels. Preferably, the first chamber and the second chamber are fluidically connected by 1 to 10,000,000, preferably 20 to 500,000, and more preferably 50 to 200,000 channels. Typically, the channels are arranged essentially parallel to each other.

For example, the channel(s) may have a diameter of between 0.25 and 2000 µm, preferably between 0.5 and 800 µm, more preferably between 1 and 500 µm, or even between 2 and 250 µm. The multiple channels of the membrane are typically microchannels. For example, each channel may have a cross-section of 0.04 µm ² to 4,000,000 µm ² , preferably from 4 µm ² to 640,000 µm ² .

According to a first embodiment, all the channels have an identical diameter, which makes it possible to obtain monodisperse drops.

According to a second embodiment, the channels have different diameters, which makes it possible to obtain polydisperse drops, with controlled polydispersity.

In other embodiments, the ratio "channel length / minimum diameter" may be between 5 and 1000, preferably between 10 and 500, in particular between 10 and 50. In some embodiments, the channel length may be between 0.05 mm and 20 mm, in particular between 0.1 mm and 20 mm, in particular between 0.1 mm and 5 mm, in particular between 0.5 and 20 mm.

In some embodiments, each channel comprises a channel outlet with a cross-section that is larger than the cross-section of the remaining portion of the respective channel. In the longitudinal direction, i.e., in the flow direction, the channel outlet has a typical length of a few micrometers, e.g., 200 µm to 20 mm, preferably 500 µm to 5 mm. The channel outlet may, for example, be funnel-shaped, V-shaped, or U-shaped, as described in WO2022106361. In some embodiments, the channel outlet may have an elliptical contour. In particular, the channel outlet is not rotationally symmetrical, thus having a length-to-width ratio of 3 and higher. Therefore, the channel outlet may not have a circular or square-shaped cross-section. Such a channel outlet allows the detachment of a droplet without external force. Therefore, drop formation is decoupled and thus essentially independent of the flow rate. According to the Young-Laplace equation, the pressure at an immiscible liquid interface is higher at the channel outlet than in the second reservoir. Thus, a pressure gradient along the flow direction is generated, which causes the fluid thread to detach into individual drops. Thus, a pressure gradient is generated at the end of the channel, which facilitates the detachment of the fluid boundary layer and thus the formation of individual drops. When it reaches the channel outlet, the pressure gradient of the dispersed phase inside and outside the channel of a drop detaches without external force.

Typically, each channel is defined by channel walls. The channel walls may be curved, i.e., the channel walls may have a convex or concave shape toward the channel outlet. Furthermore, each channel may include a constriction with a cross-section that is smaller than the cross-section of the remainder of the channel and wherein the constriction is arranged adjacent to the channel outlet. Thus, the constriction is arranged between the channel outlet and the remainder of the channel.

In other embodiments, the cross-sectional area of each channel outlet is from 0.12 to 36,000,000 µm ² , preferably from 12 to 5,760,000 µm ² . In particular, the total open area of the second side of the membrane may be from 300% to 1,500%, preferably from 400% to 900%, greater than the total open area of the channels at any other given position, such as the main section and/or the channel inlets.

In some embodiments, the one or more channels may be comprised in a membrane separating the first chamber from the second chamber. In such embodiments, the membrane may be flat, for example, disc-shaped. The membrane typically has a first side facing the first chamber and a second side, opposite the first side and facing the second chamber. Thus, the first side of the membrane may partially limit the first chamber and the second side of the membrane may partially limit the second chamber. The one or more channels, typically multiple channels, extend from the first side to the second side through the membrane. Each channel includes a channel inlet disposed on the first side, a channel outlet disposed on the second side, and a main section disposed between the channel inlet and the channel outlet.

The membrane can typically be a single-layer membrane. That is, the membrane is made of a single piece. Preferably, such a membrane is made of a solid material and does not contain any phase interfaces or transition zones in addition to the multiple channels of the membrane. Such a membrane is advantageous for the quality of the generated drops, since all interfaces and phase transitions are detrimental to the formation and stability of the drops.

In some embodiments, the membrane may be exchangeable. The multiple channels of the membrane are typically microchannels. For example, each channel may have a cross-sectional area of 0.04 µm ² to 4,000,000 µm ² , preferably 4 µm ² to 640,000 µm ² .

In other embodiments, the channel outlet may be wedge-shaped. In particular, the channel outlet may comprise an elliptical cross-section with respect to a transverse plane perpendicular to the extending channel, i.e., the channel outlet may be larger in a first direction than in a second direction. In other embodiments, the second side of the membrane comprises a total open area that is greater than the total open area of the first side. Such a membrane has the advantage of generating high-quality drops, even at flow rates up to 5 L/h. In some embodiments, the flow rate per channel may be between 1 µl/h and 50 ml/h, preferably between 10 µl/h and 5 ml/h.

In some embodiments, each channel outlet may have an elliptical contour. Thus, the channel outlet may have an elliptical cross-section with respect to a plane being transverse to the extending channel and being parallel to the first or second side of the membrane. Channel outlets with an elliptical contour have a beneficial effect on the quality of the drops formed, as any edges within the channel may lead to unstable and inhomogeneous drops.

In some embodiments, the membrane is disc-shaped. Such a membrane may have a circular outline. Alternatively, the membrane may have an angular outline, such as triangular or rectangular.

In other embodiments, the membrane comprises 0.06 to 600,000 channels/cm ² , preferably 20 to 30,000 channels/cm ² .

In some embodiments, the membrane is made of glass or a polymeric material, such as poly(methyl meth)acrylate or PTFE or a metallic material, such as steel.

Fat phase

Step a. consists of providing in the first chamber a liquid fatty phase comprising at least one oil and optionally at least one lipophilic gelling agent, preferably a heat-sensitive lipophilic gelling agent.

For the purposes of the present invention, the term “liquid fatty phase” means a non-solid fatty phase (or solution) and in particular capable of flowing under its own weight and passing through the channels between the first and second chambers.

The viscosity of the fatty phase in step a. is advantageously less than 500 cP (or mPa.s), preferably less than 250 cP, in particular less than 100 cP, better still less than 50 cP, and very particularly less than 25 cP.

A viscosity can be measured according to the method described in WO2017046305.

If necessary, the liquid character of the fatty phase in step a. can be obtained by heating this fatty phase to a temperature above its melting point, and in particular to a temperature above the highest melting point among the lipophilic gelling agent(s) when present.

In particular, the fatty phase can be heated to a temperature between 50°C and 150°C, preferably between 60°C and 110°C, and better still between 70°C and 90°C.

Advantageously, the first chamber comprises a heating member to maintain the fatty phase at a temperature above its melting point and thus guarantee that this fatty phase remains fluid in the first chamber and for carrying out step c.

For obvious reasons, the dispersed fatty phase and the continuous aqueous phase are substantially immiscible.

By “substantially immiscible” within the meaning of the present invention, it is meant that the solubility of a first phase in a second phase is advantageously less than 5% by mass, and vice versa.

According to one embodiment, a dispersion according to the invention advantageously comprises between 1% and 70%, preferably between 5% and 50%, better still between 10% and 40%, and very particularly between 15% and 30%, by weight of fatty phase relative to the total weight of the dispersion.

Oils)

The term "oil" means a fatty substance that is liquid at room temperature.

Examples of oils that can be used according to the invention include:

- hydrocarbon oils of vegetable origin, such as hydrogenated jojoba oil, hydrogenated sunflower oil, hydrogenated castor oil, hydrogenated coconut oil;

- hydrocarbon oils of animal origin, such as perhydrosqualene and squalane;

- synthetic esters and ethers, in particular of fatty acids, such as oils of formulas R1COOR2 and R1OR2 in which R1 represents the residue of a fatty acid in C8 to C29, and R2 represents a hydrocarbon chain, branched or not, in C3 to C30, such as for example Purcellin oil, isononyl isononanoate, isodecyl neopentanoate, isopropyl myristate, ethyl-2-hexyl palmitate, octyl-2-dodecyl stearate, octyl-2-dodecyl erucate, isostearyl isostearate; hydroxylated esters such as isostearyl lactate, octylhydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate, triisocetyl citrate, fatty alcohol heptanoates, octanoates, decanoates; polyol esters, such as propylene glycol dioctanoate, neopentyl glycol diheptanoate and diethylene glycol diisononanoate; and pentaerythritol esters such as pentaerythrityl tetrabehenate (DUB PTB) or pentaerythrityl tetraisostearate (Prisorine 3631);

- linear or branched hydrocarbons, of mineral or synthetic origin, such as paraffin oils, volatile or not, and their derivatives, petroleum jelly, polydecenes, hydrogenated polyisobutene such as Parléam oil;

- silicone oils, such as volatile or non-volatile polymethylsiloxanes (PDMS) with a linear or cyclic silicone chain, liquid or pasty at room temperature, in particular cyclopolydimethylsiloxanes (cyclomethicones) such as cyclohexasiloxane and cyclopentasiloxane; polydimethylsiloxanes (or dimethicones) comprising alkyl, alkoxy or phenyl groups, pendant or at the end of the silicone chain, groups having from 2 to 24 carbon atoms; phenyl silicones such as phenyltrimethicones, phenyldimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyldimethicones, diphenylmethyldiphenyl trisiloxanes, 2-phenylethyltrimethylsiloxysilicates, and polymethylphenylsiloxanes;

- fatty alcohols with 8 to 26 carbon atoms, such as cetyl alcohol, stearyl alcohol and their mixture (cetylstearyl alcohol), or octyldodecanol;

- partially hydrocarbon and/or silicone fluorinated oils such as those described in document JP-A-2-295912;

- and their mixtures.

According to a preferred embodiment, the oil is selected from the group consisting of isononyl isononanoate, dimethicone, isohexadecane, polydimethylsiloxane, octyldodecanol, isodecyl neopentanoate and mixtures thereof.

According to another preferred embodiment, the fatty phase does not comprise silicone oil, and preferably does not comprise polydimethylsiloxane (PDMS).

A person skilled in the art will know how to adjust the nature and/or the content of oil(s), in particular to ensure satisfactory stability of the dispersion according to the invention and to retain the aforementioned advantageous technical effects.

According to one embodiment, a dispersion according to the invention advantageously comprises between 50% and 99%, preferably between 60% and 90%, and better still between 70% and 80%, by weight of oil(s) relative to the total weight of the fatty phase, or even of the core of the drops when the latter comprise an envelope.

Lipophilic gelling agent

A lipophilic gelling agent, i.e. soluble or dispersible in the fatty phase, may be chosen from organic or mineral, polymeric or molecular gelling agents; fatty substances which are solid at room temperature and pressure, in particular chosen from waxes, pasty fatty substances, butters; and mixtures thereof, and preferably from polymeric gelling agents.

Such lipophilic gelling agents are notably described in WO2019002308.

Among the lipophilic gelling agents that can be used in the present invention, mention may be made of dextrin and fatty acid esters, such as dextrin palmitates. Among the dextrin and fatty acid esters, mention may be made, for example, of dextrin palmitates, dextrin myristates, dextrin palmitates/ethylhexanoates and mixtures thereof. Mention may in particular be made of the dextrin and fatty acid esters marketed under the names Rheopearl® KL2 (INCI name: dextrin palmitate), Rheopearl® TT2 (INCI name: dextrin palmitate ethylhexanoate), and Rheopearl® MKL2 (INCI name: dextrin myristate) by the company Miyoshi Europe, also dextrin palmitate marketed by The Innovation Company.

Other examples include THIXCIN® R from Elementis Specialties (INCI: Trihydroxystearin), OILKEMIA™ 5S polymer from Lubrizol (INCI: Caprylic/Capric Triglyceride (and) Polyurethane-79), Estogel M from PolymerExpert (INCI: CASTOR OIL / IPDI COPOLYMER & CAPRYLIC / CAPRIC TRIGLYCERIDE), Hydrogenated Castor Oil/Sebacic Acid Copolymer and its derivatives, notably marketed respectively under the names Estogel Green (or Estogel G) and Estogel Green 40 by PolymerExpert, and their mixtures.

Advantageously, a lipophilic gelling agent is a heat-sensitive gelling agent, that is to say a gelling agent which reacts to heat, and in particular which is solid at room temperature and liquid at a temperature above 50°C, preferably above 60°C.

Advantageously, a lipophilic gelling agent is a thixotropic gelling agent or one capable of giving the fatty phase thixotropic behavior. Such a thixotropic gelling agent is in particular chosen from pyrogenic silicas which may be hydrophobically treated.

According to the invention, a dispersion according to the invention may comprise between 0.5% and 30%, preferably between 1% and 25%, in particular between 1.5% and 20%, better still between 2% and 15%, and very particularly between 5% and 12%, by weight of lipophilic gelling agent(s) relative to the total weight of the fatty phase.

According to a particular embodiment, the fatty phase may further comprise at least one, preferably a single, internal drop of an internal phase substantially immiscible with the fatty phase. In this case, the fatty phase may also be designated as “intermediate phase” or “intermediate fatty phase”.

According to this embodiment, the dispersed phase can be referred to as an “inverse emulsion”.

Advantageously, the inverse emulsion comprises an “internal phase/intermediate phase” weight ratio of between 1 and 50, preferably between 2 and 25, better still between 3 and 10, and particularly between 4 and 5.

According to a first variant, the internal phase can be a fatty phase. Pairs of immiscible oils are notably described in FR3063893.

According to a second variant, the internal phase may be an aqueous phase, identical or different, preferably different, from the aqueous phase of step b. This variant embodiment is particularly useful when seeking to form capsules, as described in WO2022106361.

Compound(s) of interest

In certain embodiments, the fatty phase of step a. and/or the internal phase when present, may further comprise at least one compound of interest. A compound of interest may be chosen from a biological active agent, a pharmaceutical active agent and/or a cosmetic active agent, for example chosen from moisturizing agents, healing agents, depigmenting agents, UV filters, desquamating agents, antioxidant agents, active agents stimulating the synthesis of dermal and/or epidermal macromolecular agents, dermo-contracting agents, antiperspirant agents, soothing agents, anti-aging agents, perfuming agents, anticoagulants, anti-thrombogenic agents, anti-mitotic agents, anti-proliferation, anti-adhesion, anti-migration agents, cell adhesion promoters, growth factors, antiparasitic molecules, anti-inflammatories, angiogenic agents, angiogenesis inhibitors, vitamins, hormones, proteins, antifungals, antimicrobial molecules, antiseptics or antibiotics, flavorings, antibodies, peptides, enzymes, RNA, DNA, microorganisms, and mixtures thereof.

Of course, the person skilled in the art will take care to choose the possible compound(s) of interest and/or their quantity with regard to the nature of the phase considered and in such a way that the advantageous properties of a dispersion and of the manufacturing process according to the invention are not or are not substantially altered by the envisaged addition. These adjustments fall within the general knowledge of the person skilled in the art.

Aqueous phase

Step b. consists of providing in the second chamber a liquid aqueous phase comprising water and at least one hydrophilic gelling agent.

For the purposes of the present invention, the term “liquid aqueous phase” means a non-solid aqueous phase capable of ensuring the formation of drops of fatty phase during step c.

The viscosity of the aqueous phase in step b. is advantageously less than 500 cP (or mPa.s), preferably less than 250 cP, in particular less than 100 cP, better still less than 50 cP, and very particularly less than 25 cP.

If necessary, the liquid character of the aqueous phase in step b. can be obtained by heating this aqueous phase to a temperature above its melting point, and in particular to a temperature above the highest melting point among the heat-sensitive hydrophilic gelling agent(s) present.

In particular, the aqueous phase may be heated to a temperature between 50°C and 150°C, preferably between 60°C and 110°C, and better still between 70°C and 90°C.

Advantageously, the second chamber comprises a heating member to maintain the aqueous phase at a temperature above its melting point and thus guarantee that this aqueous phase remains fluid in the microfluidic device, in particular for carrying out step c.

In view of the above:

- during step c., the liquid aqueous phase can be characterized as “non-gelled aqueous phase” or “non-suspensive aqueous phase” with respect to the drops; and

- after step d., the aqueous phase can be characterized as a “gelled aqueous phase” or a “suspensive aqueous phase” with respect to the drops.

In particular, it is the gelled aqueous phase, and therefore the aqueous phase obtained at the end of step d., which confers in whole or in part the suspension, and therefore the stability, of a dispersion according to the invention.

In particular, the gelled aqueous phase has a flow threshold value suitable for ensuring the suspension (or suspensivity) of the drops over a period of time greater than or equal to 1 month, preferably greater than or equal to 3 months, better still greater than or equal to 6 months, and particularly greater than or equal to 12 months.

Thus, at room temperature and atmospheric pressure, the aqueous phase obtained at the end of step d. advantageously has a flow threshold greater than 0.1 Pa, in particular greater than 1 Pa, and preferably between 0.5 Pa and 100 Pa, in particular between 1 Pa and 75 Pa, very particularly between 2 Pa and 50 Pa, or even between 5 Pa and 25 Pa, and better still between 10 Pa and 20 Pa.

The yield stress is measured at room temperature and ambient pressure by the flow shear rate sweep method described in H.A. Barnes, A Handbook of Elementary Rheology; Institute of Non-Newtonian Fluid Mechanics. University of Wales, 2000 or http://www.tainstruments.com/pdf/literature/RH025.pdf.

Preferably, the aqueous phase of a dispersion according to the invention, in particular after step d., is transparent or at least translucent. The property of transparency or translucency can be determined according to the method described in WO2018/167309.

The aqueous phase is advantageously a non-Newtonian fluid. It is advantageously a shear-thinning fluid.

Water

An aqueous phase or aqueous solution according to the invention comprises water. In addition to distilled or deionized water, water suitable for the invention may also be natural spring water or floral water.

According to one embodiment, the mass percentage of water in the aqueous phase is at least 50%, and better still at least 60%, in particular between 70% and 98%, and preferably between 75% and 95%, relative to the total mass of said dispersed aqueous phase.

Hydrophilic gelling agent(s)

In the context of the present invention, a hydrophilic gelling agent makes it possible, after exposure of the aqueous phase to at least one gelling inducer, to increase the viscosity and the flow threshold of said aqueous phase and thus to acquire suspensive properties with respect to the drops of fatty phase. The hydrophilic gelling agent also makes it possible to modulate the fluidity, texture and sensoriality of the dispersion.

The aqueous phase may comprise at least one hydrophilic gelling agent chosen from:

- an ion-sensitive gelling agent, in which case the gelling-inducing agent is at least one salt;

- a pH-sensitive gelling agent, in which case the gelling-inducing agent is at least one base, preferably an alkali hydroxide, and better still sodium hydroxide;

- a heat-sensitive gelling agent, in which case the gelling-inducing agent is at least one temperature lowering agent; and/or

- a light-sensitive gelling agent, in which case the gelling-inducing agent is at least light, in particular visible or UV light; and

- their mixtures.

A person skilled in the art will know how to adjust the nature and content of hydrophilic gelling agent(s) to satisfy the aforementioned viscosity and flow threshold criteria.

Preferably, the aqueous phase comprises between 0.01% and 5%, preferably between 0.05% and 2.5%, better still between 0.05% and 1%, and very particularly between 0.08% and 0.5%, by weight of hydrophilic gelling agent(s) relative to the total weight of the aqueous phase, or even relative to the total weight of the dispersion.

Gelling agent ion-sensitive

An ion-sensitive gelling agent is a hydrophilic gelling agent capable of gelling in the presence of at least one salt. For obvious reasons, it is appropriate to adapt the nature, or even the content, of ion-sensitive gelling agent with regard to the salt(s) used as gelling inducer in step d. This adaptation falls within the general skills of the person skilled in the art.

Preferably, the ion-sensitive gelling agent is a polyelectrolyte reactive to at least one salt, in particular in the presence of at least one monovalent or divalent ion such as for example K ⁺ , Na ⁺ , Ca ⁺⁺ or Mg ⁺⁺ .

An ion-sensitive gelling agent may be selected from natural polymers, biosynthetic polymers, modified polymers, and mixtures thereof. Preferably, the ion-sensitive gelling agent is selected from natural polymers.

Preferably, an ion-sensitive gelling agent may be chosen from alginate, pectin, in particular Low Methoxyl pectin, carrageenan, in particular iota-carrageenan, gellan gum, furcellaran, or one of their derivatives, and their mixtures.

Preferably, an ion-sensitive gelling agent may be chosen from alginate, gellan gum and/or carrageenan, and very particularly from gellan gum and/or iota-carrageenan.

Advantageously, the ion-sensitive gelling agent is not chosen from algin or alginate.

Preferably, the ion-sensitive gelling agent is not a thermosensitive hydrophilic gelling agent.

pH-sensitive gelling agent

A pH-sensitive gelling agent is a hydrophilic gelling agent capable of gelling in the presence of at least one base, preferably an alkali metal hydroxide, and more preferably sodium hydroxide. For obvious reasons, it is appropriate to adapt the nature, or even the content, of the pH-sensitive gelling agent with regard to the base used as a gelling inducer in step d. This adaptation falls within the general skills of the person skilled in the art.

Also, before step d., it may be necessary to adjust the pH of the aqueous phase so that the latter has the expected liquid character. This adjustment falls within the general skills of a person skilled in the art. Preferably, before step d., when the aqueous phase comprises at least one pH-sensitive gelling agent as a hydrophilic gelling agent, the pH of the corresponding aqueous phase in step b. is less than 4, and better still less than 3. Thus, the aqueous phase of step b. may further comprise at least one acid.

A pH-sensitive gelling agent may be selected from an anionic polymer, preferably a carbomer. This polymer may also be a crosslinked acrylates/C ₁₀ - ₃₀ alkyl acrylate copolymer (INCI name: acrylates/C ₁₀ - ₃₀ alkyl acrylate Crosspolymer).

In the context of the invention, and unless otherwise stated, the term "carbomer" means an optionally crosslinked homopolymer, resulting from the polymerization of acrylic acid, or a copolymer or derivative of acrylic acid. It is therefore an optionally crosslinked poly(acrylic acid). Carbomers have other names, in particular "polyacrylic acids", "carboxyvinyl polymers" or "carboxy polyethylenes".

According to one embodiment, the term "carbomer" or "carbomer" or "Carbopol ^® " means a high molecular weight acrylic acid polymer crosslinked with allyl sucrose or allyl ethers of pentaerythritol (handbook of Pharmaceutical Excipients, 5th ^Edition , plll). For example, these are Tego ^® Carbomer 340FD from Evonik, or Carbopol ^® 910, Carbopol ^® 934, Carbopol ^® 934P, Carbopol ^® 940, Carbopol ® 941, Carbopol ^® 71G, Carbopol ^® 980, Carbopol ^® 981, Carbopol ^® 971P, Carbopol ETD 2050 ^, Carbopol ^® 974P, Carbopol Ultrez 10, all marketed by Lubrizol, and their mixtures.

Thermosensitive gelling agent

A heat-sensitive gelling agent is a hydrophilic gelling agent capable of gelling in the presence of at least one reduction in temperature, preferably at a temperature below 50°C, better still below 40°C, in particular below or equal to room temperature, or even below or equal to 10°C.

For obvious reasons, it is appropriate to adapt the nature, or even the content of the heat-sensitive gelling agent with regard to the desired heating and/or cooling temperatures. This adaptation falls within the general skills of the person skilled in the art.

Preferably, the thermosensitive hydrophilic gelling agent is chosen from natural polymers, biosynthetic polymers, modified polymers, and mixtures thereof, preferably from natural polymers.

Preferably, the thermosensitive hydrophilic gelling agent is chosen from agar, kappa carrageenan, konjac, gelatin, and mixtures thereof.

Light-sensitive gelling agent

A light-sensitive gelling agent is a hydrophilic gelling agent capable of gelling in the presence of at least one light, in particular visible or UV light.

For obvious reasons, it is appropriate to adapt the nature, or even the content, of the light-sensitive gelling agent to the light source used. This adaptation falls within the general skills of the person skilled in the art.

According to a particular embodiment, when the aqueous phase comprises at least one light-sensitive gelling agent as hydrophilic gelling agent, the aqueous phase may further comprise at least one crosslinking agent, and optionally further at least one photoinitiator and/or at least one catalyst.

A light-sensitive gelling agent according to the invention may be chosen from at least one monomer or at least one polymer. According to the invention, the term “monomer” or “polymer” designates any basic unit suitable for the formation of a solid material by polymerization, either alone or in combination with other monomers or polymers.

A monomer may be chosen from monomers comprising at least one reactive function chosen from the group consisting of acrylate, methacrylate, vinyl ether, N-vinyl ether, mercaptoester, thiolene, siloxane, epoxy, oxetane, urethane, isocyanate and peroxide functions. In particular, the monomers may be chosen from monomers carrying at least one of the aforementioned reactive functions and further carrying at least one function chosen from the group consisting of primary, secondary and tertiary alkylamine functions, quaternary amine functions, sulfate, sulfonate, phosphate, phosphonate, carboxylate, hydroxyl, halogen functions, and mixtures thereof.

A polymer may be chosen from polyethers, polyesters, polyurethanes, polyureas, polyethylene glycols, polypropylene glycols, polyamides, polyacetals, polyimides, polyolefins, polysulfides and polydimethylsiloxanes, said polymers also carrying at least one reactive function chosen from the group consisting of acrylate, methacrylate, vinyl ether, N-vinyl ether, mercaptoester, thiolene, siloxane, epoxy, oxetane, urethane, isocyanate and peroxide functions, and mixtures thereof.

Advantageously, a cosmetic-grade monomer or polymer is used. Advantageously, a biodegradable monomer or polymer is used. A biodegradable monomer or polymer may in particular be chosen from CN2035 and/or CN2203 (polyester acrylate oligomer) marketed by the company Sartomer.

By "crosslinking agent" is meant a compound carrying at least two reactive functions capable of crosslinking a monomer or a polymer, or a mixture of monomers or polymers, during its polymerization. The crosslinking agent may be chosen from molecules carrying at least two functions chosen from the group consisting of acrylate, methacrylate, vinyl ether, N-vinyl ether, mercaptoester, thiolene, siloxane, epoxy, oxetane, urethane, isocyanate and peroxide functions, and mixtures thereof.

The term “photoinitiator” means a compound capable of fragmenting under the effect of light radiation. The photoinitiators that can be used according to the present invention are known in the art and are described, for example, in “Photoinitiators in the crosslinking of coatings”, G. Li Bassi, Double Liaison – Chimie des Peintures, No. 361, November 1985, pp. 34-41; “Industrial applications of photoinduced polymerization”, Henri Strub, L'Actualité Chimique, February 2000, pp. 5-13; and “Photopolymers: theoretical considerations and setting reaction”, Marc, J.M. Abadie, Double Liaison – Chimie des Peintures, No. 435–436, 1992, pp. 28-34.

The catalyst may be chosen from organic, metallic, organometallic or inorganometallic catalysts, and mixtures thereof. As catalyst, mention may in particular be made of organometallic or inorganometallic complexes of platinum, palladium, titanium, molybdenum, copper, zinc, and mixtures thereof.

As light-sensitive gelling agents, crosslinking agents, photoinitiators and catalysts which can be used in the present invention, mention may be made in particular of those described in WO2018172433.

Gelation inducer(s)

In view of the above, a gelling inducer may be an ingredient and/or a parameter which, after having been exposed to the aqueous phase of the dispersion obtained in step c., makes it possible to “activate” the hydrophilic gelling agent, and thus to increase the viscosity and the flow threshold of said aqueous phase, and thus to form a stable, and therefore suspensive, dispersion.

In view of the above, a gelation inducer may be chosen from:

- a salt when the hydrophilic gelling agent is at least one ion-sensitive gelling agent;

- a base, preferably an alkali hydroxide, and better still sodium hydroxide, when the hydrophilic gelling agent is at least one pH-sensitive gelling agent;

- a lowering of the temperature when the hydrophilic gelling agent is a thermosensitive gelling agent;

- light, in particular visible or UV light, when the hydrophilic gelling agent is a light-sensitive gelling agent. Preferably, the inducing agent is at least one UV light emitting in the wavelength range between 100 nm and 400 nm, and in particular for a duration of less than or equal to 15 minutes; and

- their mixtures.

When the gelling inducer is an ingredient, the latter is advantageously added to the continuous phase of the dispersion obtained in step c. in the form of an additional solution miscible with the aqueous phase of step b. This embodiment is therefore not applicable in the case where the gelling inducer is a parameter such as a lowering of the temperature.

By “miscible” in the sense of the present invention, it is meant that the solubility of the additional solution in the aqueous phase of the dispersion of step c. is advantageously greater than 5% by mass, and vice versa.

Thus, step d. consists of injecting into the aqueous phase of the dispersion obtained in step c. at least one additional solution which preferably comprises at least water and at least one gelling inducer.

According to one embodiment, the additional solution comprises between 0.01% and 30%, preferably between 0.1% and 20%, in particular between 1% and 15%, and in particular between 2% and 10%, by weight of gelling inducer(s) relative to the total weight of the additional solution.

When the drops of a dispersion according to the invention comprise a shell, a person skilled in the art will know how to adjust the content of hydrophilic gelling agent(s) and/or gelling inducer(s), in particular pH-sensitive hydrophilic gelling agent(s), in such a way that said hydrophilic gelling agent(s) and/or gelling inducer(s) do not alter or only slightly alter the integrity of the shell. A person skilled in the art will even know how to adjust the content of hydrophilic gelling agent(s) and/or gelling inducer(s), in particular sensitive hydrophilic gelling agent(s), in such a way as to control any possible reduction in the mechanical strength of the shell, and thus reduce any possible residual shell phenomenon upon application.

As previously stated, steps c. and d. can be performed simultaneously.

Indeed, step d. of exposing the aqueous phase to at least one gelling inducer of the hydrophilic gelling agent can be carried out in the second chamber and/or after leaving the second chamber.

Preferably, step d. is carried out after exiting the second chamber.

According to a particular embodiment, a method according to the invention comprises at least two steps d1. and d2., identical or different.

Such an embodiment is advantageous, in particular when a manufacturing method according to the invention requires, between the manufacturing of the dispersion and its packaging in the final packaging, intermediate packaging in a storage tank. Such a storage tank may for example be a bucket or an IBC container (“Intermediate bulk container”, also referred to as an IBC container (“Large Bulk Container”). This is particularly the case when the manufacturing method according to the invention is implemented on an industrial scale.

So, for example:

- step d1. provides access to a dispersion that is sufficiently suspensive to ensure satisfactory stability of the dispersion in the storage tank while retaining a sufficiently liquid character to guarantee subsequent packaging of this “pre-gelled” dispersion in the final packaging; and

- step d2. provides access to a dispersion whose aqueous phase has reached its final viscosity, this step d2. preferably being carried out simultaneously with the conditioning of the dispersion from step d1. in the final packaging, thus guaranteeing easy conditioning of the dispersion and without alteration of the drops in the final packaging.

Preferably, step d1. is carried out in the second chamber, between the second chamber and the storage tank and/or simultaneously with the conditioning of the dispersion from step c. in the storage tank.

Salts)

In some embodiments, the gelation inducer is at least one salt.

For obvious reasons, the salt is chosen from a salt capable of reacting with the ion-sensitive hydrophilic gelling agent. In other words, the choice of salt(s) should be adapted to the ion-sensitive gelling agent(s).

A salt according to the invention may be chosen from a monovalent salt, preferably from sodium salts such as sodium chloride, potassium salts such as potassium chloride; and/or multivalent, in particular divalent, preferably from calcium salts such as calcium carbonate, magnesium salts such as magnesium sulfate, and mixtures thereof, and preferably the salt is a monovalent salt, in particular sodium chloride.

Drops

The dispersed fatty phase of a dispersion according to the invention is in the form of drops, all or part of the drops preferably being macroscopic, that is to say visible to the naked eye.

In the remainder of this description, the drops of fatty phase may be referred to interchangeably as “drop (G1)”.

Advantageously, in a dispersion of step d., the drops have an average diameter of between 150 μm and 3,000 μm, preferably between 250 μm and 2,000 μm, in particular between 500 μm and 1,500 μm, and better still between 750 μm and 1,000 μm, preferably with a coefficient of variation of less than or equal to 10%, preferably less than or equal to 5%, and better still less than or equal to 3%.

Thus, in a dispersion according to the invention, the phases constituting it form a macroscopically inhomogeneous mixture.

The drops are advantageously substantially spherical.

Advantageously, the drops advantageously exhibit an apparent monodispersity (i.e. they are perceived by the eye as spheres of identical diameter).

Preferably, the dispersions of the invention consist of a population of monodisperse drops, in particular such that they have an average diameter from 100 µm to 3,000 µm, in particular from 500 µm to 3,000 µm and a coefficient of variation Cv of less than 10%, or even less than 3%.

According to a first embodiment, the drops of a dispersion according to the invention are devoid of an envelope (or “shell” or “membrane”), in particular of a polymeric membrane or formed by interfacial polymerization. In particular, the drops of a dispersion according to the invention are not stabilized using a coacervate membrane (anionic polymer (carbomer)/cationic polymer (amodimethicone) type).

In other words, the contact between the aqueous continuous phase and the dispersed fatty phase is direct.

According to another embodiment, the drops of a dispersion according to the invention may comprise a core formed at least from the fatty phase and an envelope.

The envelope can be referred to interchangeably by the terms “membrane” or “bark”.

The envelope completely encapsulating the fatty phase, which can then be referred to interchangeably as the “core”, is advantageously a gelled envelope and/or an envelope deriving from a complex coacervation reaction.

Preferably, the envelope is an aqueous phase. Preferably, the envelope is transparent. Advantageously, the envelope has a homogeneous thickness.

By “homogeneous thickness”, for the purposes of the present invention, is meant droplets whose bark thickness varies according to a standard deviation less than or equal to 10%, preferably less than or equal to 5%.

Any modifications and/or adaptations of the manufacturing process according to the invention which may prove necessary in the case where the drops comprise an envelope fall within the general skills of those skilled in the art.

By way of illustration, when the envelope derives from a complex coacervation reaction, the fatty phase of step a. may further comprise a first precursor polymer of the coacervate, for example a lipophilic cationic polymer, such as for example amodimethicone, and the aqueous phase of step b. may further comprise a second precursor polymer of the coacervate, for example a hydrophilic anionic polymer, such as for example a carbomer. Such an embodiment is notably described in more detail in WO2012120043 or the patent applications filed under Nos. FR2205167 and FR2205168.

By way of illustration, when the shell is a gelled shell, reference may be made to WO2022106361 which describes in particular the presence of a gelling inducing agent and a shell forming agent configured such that they are capable of undergoing a chemical reaction with each other to form a water-insoluble matrix shell, these being able for example to be configured to undergo a complexation reaction, an ion exchange reaction or an interphase limited polymerization reaction.

Preferably, the shell of the drops may be derived from the reaction of at least one water-soluble matrix-forming agent (or “matrix agent”) with at least one gelation-inducing agent, as described in WO2022106361.

In some embodiments, step c. and step d. are carried out at temperatures above room temperature, in particular between 25°C and 95°C, in particular between 40°C and 85°C, in particular between 50°C and 80°C, in particular between 65°C and 80°C, in particular between 70°C and 80°C.

In other embodiments, a pressure of 1.01 bar to 1.15 bar, preferably 1.03 bar to 1.07 bar is applied to the first chamber, in particular during step c., and/or a pressure of 1.02 bar to 1.2 bar, preferably 1.05 bar to 1.1 bar is applied to the second chamber, in particular during step c. It is understood that these pressure values relate to absolute pressures, i.e. a pressure of 1.01 bar is a pressure which constitutes an overpressure of 0.01 bar relative to atmospheric pressure.

In some embodiments, the pressure applied to the first chamber is lower than the pressure applied to the second chamber. It is understood that the first pressure may be adjusted by the pressure with which the fatty phase of step a. is supplied via the first fluid inlet from the first chamber to the first chamber and/or the second pressure may be adjusted by the pressure with which the second aqueous solution of step b. is supplied via the second fluid inlet from the second chamber to the second chamber.

In some embodiments, step d. comprises stirring, preferably the stirring is carried out with a stirrer with stirring speed of 10 rpm to 800 rpm, preferably 25 rpm to 500 rpm, in particular 50 rpm to 350 rpm, and more preferably 100 rpm to 150 rpm. Stirring during step d. is advantageous because it ensures uniform drop size distribution and prevents the risk of agglomerations. Typically, an overhead stirrer or a stirring device as described in WO2023/099530 may be employed.

In view of the above, an agitator may be present in the second chamber and/or after the outlet of the second chamber.

In some embodiments, step d. is carried out for 5 min to 25 min, preferably for 8 min to 12 min or for 15 min to 20 min. The reaction time of step d. can directly influence the droplet size.

According to one embodiment, after step d., the drops of the dispersion according to the invention can be isolated, hardened and/or preserved.

Isolation of the drops may for example comprise filtration or sieving in order to separate the drops from the gelled aqueous phase, and optionally washing the drops with water optionally comprising at least one surfactant, such as sodium lauryl sulfate (SDS), a Tween derivative, such as Tween 20 or 80, or PVA.

Curing may for example comprise drying the drops, for example by an air stream or by freeze-drying, in order to evaporate all or at least the majority of the unbound water. Curing may also comprise further agitation of the drops in an aqueous solution comprising at least one inorganic salt, such as CaCl ₂ or MgCl ₂ , preferably an aqueous solution of 1% to 10%, preferably 1% to 5%, by weight of inorganic salt(s). This further increases the stability and structural integrity of the drops, in particular of the shell when present.

Preservation may be achieved by immersing the drops in distilled water or in an aqueous solution of inorganic salt, such as CaCl ₂ or MgCl ₂ , preferably a 1 to 10% aqueous solution, more preferably 1 to 5% by weight of the inorganic salt. Such preservation has been found to increase the stability of the drops.

According to another embodiment, a method according to the invention makes it possible to directly and continuously manufacture a stable dispersion which can be used directly, for example as a cosmetic composition. In other words, a manufacturing method according to this embodiment advantageously does not include any subsequent step(s) aimed at isolating, hardening and/or preserving the drops.

In some embodiments, in particular after step d. and when the drops comprise a shell, in particular based on an ion-sensitive gelling agent, and in particular alginate, the drops may be exposed to a solution comprising at least one chelating agent. The chelating agent is configured such that it can form a chelating complex with the ion-sensitive gelling agent of the shell. For example, if the chelation-inducing agent is a calcium salt, such as CaCl ₂ , the chelating agent can form a chelating complex with Ca ²⁺ . Suitable chelating agents are Lewis bases, such as EDTA, GLDA (N,N-Bis(carboxymethyl)-L-glutamate tetrasodium), MGDA (trisodium dicarboxymethyl alaninate), citrate acid salts, tartaric acid salts and the like. The solvent is generally chosen so that the chelating agent is soluble in it and the drops formed, respectively the water-insoluble matrix, are not dissolved. Thus, a suitable solvent can be water. By exposing the drops to such a solution for a predetermined period, the shell is weakened, its mechanical strength is reduced, and any residual shell phenomena upon application are therefore reduced.

In certain embodiments, step c. is carried out with a device comprising a first inlet for feeding the fatty phase from step a., where appropriate in the form of an inverse emulsion, which opens into the first chamber, a second inlet for feeding the aqueous phase from step b., opening into the second chamber and an outlet at the level of the second chamber for collecting the dispersion. Depending on the embodiment considered for carrying out step d., the dispersion collected at the outlet of the second chamber may be a transient dispersion or a final dispersion.

Furthermore, the device comprises a membrane, in particular a membrane as described above, which separates the first chamber and the second chamber and which comprises a first side facing the first chamber and a second side facing the second chamber. The membrane comprises multiple channels extending from the first side to the second side, i.e., providing a fluid connection of the first chamber and the second chamber. Each channel comprises a channel inlet arranged on the first side and a channel outlet arranged on the second side. The first chamber may typically be configured such that a flow rate of the fatty phase of step a. through all individual channels is essentially equal. In the prior art, an inhomogeneous distribution of pressures, in particular of the core emulsion, allows only a small percentage of channels to actively produce drops. An equal distribution of pressure on the first side allows a smooth flow of the fatty phase of step a. in the aqueous phase of step b. and generating drops with reproducible quality with a high flow rate of up to 5 liters per hour. The first chamber can typically be configured so that a flow rate of fatty phase from step a. through all individual channels is essentially equal.

In some embodiments, the second chamber may be made of glass or a transparent polymer, such as PTFE, poly(methyl meth)acrylate, or polyoxymethylene, or metals such as steel, aluminum, or titanium. Generally, the device may include a container, such as a glass container, that partially forms the second chamber. Together with the membrane, the container may form the second chamber. In some embodiments, the first chamber may be made of metal, for example, aluminum or steel, or a transparent polymer, such as PTFE, poly(methyl meth)acrylate, or polyoxymethylene.

The outlet of the second chamber may, for example, be in fluid communication with an intermediate container as described previously or with final packaging.

In some embodiments, the dispersion is recovered from the second chamber via the outlet of the second chamber continuously, thereby increasing production efficiency.

In certain embodiments, step d. is carried out under continuous flow of the dispersion formed in step c. Thus, according to a preferred embodiment, steps c. and d. are carried out continuously, thereby making it possible to increase the production yield.

Step d. is carried out in the second chamber and/or after exiting the second chamber.

Preferably, the drops of fatty phase, after step c. but before step d., are in a gelled state, in particular so as to optimize their mechanical strength and therefore to avoid altering their integrity. Thus, between steps c. and d., the drops of fatty phase advantageously undergo a step adapted to change these drops from a liquid form to a gelled form. This intermediate step of gelling the drops of fatty phase can be carried out by any technique known to those skilled in the art and, if necessary, adapted with regard to the type of gelling agent, in particular hydrophilic, used. In particular, the device can comprise a cooler positioned at the second chamber and/or after the outlet of the second chamber so as to accelerate the cooling kinetics of the drops of fatty phase and thus optimize their mechanical strength.

Preferably, step d. is carried out upstream of the container in which the dispersion is packaged. This container may be, for example, a storage tank or final packaging as mentioned above.

Preferably, the second chamber and the container are fluidically connected.

When step d. is carried out in the second chamber and the gelling inducer is an ingredient, then the second chamber further comprises a third inlet allowing the injection of the gelling inducer, or of the additional solution comprising said ingredient, into the second chamber.

Preferably, when step d. is carried out after leaving the second chamber and the gelling inducer is an ingredient, the injection of the gelling inducer, or of the additional solution comprising said ingredient, is preferably carried out in the immediate vicinity of the outlet of the second chamber so as to prevent the phenomena of clumping and/or phase shift of the transient dispersion.

When step d. is carried out in the second chamber and the gelling inducer is a parameter, in particular a lowering of the temperature and/or a supply of light, then the second chamber further comprises a cooler and/or a lamp and/or the second chamber is transparent to allow an external light source to reach the dispersion present in the second chamber.

Preferably, when step d. is carried out after leaving the second chamber and the gelling inducer is a parameter, in particular a lowering of the temperature and/or a supply of light, the subjection of the dispersion to this parameter is preferably carried out in the immediate vicinity of the exit of the second chamber so as to prevent the phenomena of agglutination and/or phase shift of the transient dispersion.

According to a particular embodiment, when step d. is carried out after leaving the second chamber, step d. can be carried out in an intermediate container, preferably fluidically connected to the second chamber and to the aforementioned container, or directly in the aforementioned container.

Figures 1 and 7 show an embodiment where step d. is carried out after exiting the second chamber.

In some embodiments, the first chamber is configured such that in an operative state, the pressure along the first side of the membrane is substantially isobaric. For example, the first inlet may include a nozzle to provide an isobaric pressure distribution across the first side of the membrane. In particular, a spray nozzle may be used. Alternatively, the first chamber may be shaped such that an isobaric pressure distribution across the first side of the membrane is provided.

In other embodiments, the first chamber has a rounded cross-section relative to a cross-sectional plane, which is perpendicular to the membrane and rotationally symmetrical relative to a central longitudinal axis. The term "rounded cross-section" as used herein refers to a continuous curve without increments, in particular to a curve which has in the cross-sectional plane perpendicular to the membrane, a radius of at least 1 mm, in particular at least 5 mm, in particular at least 10 mm. It is understood that the curvature in the cross-sectional view can be described as a part of a circle with said radius. Thus, the side walls of the first chamber can continuously converge towards each other in the upstream direction. The central longitudinal axis is an axis extending in the longitudinal direction of the device, which is arranged at the center of the device and/or at an axis being perpendicular to the membrane and intersecting the center of the membrane. The first chamber may have a U-shaped cross-section or may be concavely rounded or semi-circular. The rounded cross-section is typically rimless and thus excludes edges, which would lead to uneven pressure distribution when the fatty phase of step a. is forced through the membrane. Preferably, the first chamber may have the shape of a spherical dome. The shape of the first chamber may generally preferably be substantially rotationally symmetrical about the central longitudinal axis.

In some embodiments, the outlet of the second chamber may be substantially disposed on the central longitudinal axis and/or the axis being perpendicular to the membrane and intersecting the center of the membrane. Preferably, the second chamber is tapered toward the outlet of the second chamber. For example, at least portions of the second chamber may be arc-shaped or cone-shaped toward the outlet of the second chamber. These embodiments ensure that no drops are trapped and all are directly recoverable via the outlet of the second chamber. In some embodiments, the first chamber is shaped like a hemisphere or a truncated cone. Typically, the hemisphere or truncated cone opens toward the membrane, i.e., the largest radius is typically closest to the membrane. The term "hemispherical" as used herein also includes other spherical segments, such as one-third of a sphere. Thus, in some embodiments, the shape of the first chamber is a spherical dome or a spherical cap. Preferably, if the first chamber has a spherical dome shape, and/or in particular a hemispherical shape, the first inlet may be arranged adjacent to or at a pole of the spherical dome of the first chamber, in particular the hemispherical dome. Such shapes have the advantage that the material flow of the fatty phase of step a. is equally distributed on the first side of the membrane, thereby helping to provide an equal pressure distribution adjacent to the individual channel. The first inlet may for example be arranged substantially perpendicular to the central longitudinal axis, i.e., substantially parallel to the first side of the membrane, or also parallel to the central longitudinal axis.

In some embodiments, the first inlet is disposed at an angle of substantially 90° or less relative to the membrane channels. Typically, all of the channels are arranged substantially parallel to one another. This has the beneficial effect that the fatty phase from step a. is not directly forced onto the membrane, thereby further providing a uniform pressure distribution across each membrane channel. For example, the angle between the first inlet and the membrane channels may be between 60° and 90°, including 75° and 90°. Preferably, the first inlet is substantially transversely, preferably perpendicularly, to the multiple membrane channels. Thus, in such embodiments, the first inlet may be parallel to the first side of the membrane.

In other embodiments, the device comprises a membrane holder for mounting the membrane. In some embodiments, the device comprises a container holder for holding the container, which partially forms the second chamber. The container holder may be fixedly and removably connected to the membrane holder. The container holder and/or the membrane holder and/or the base may be made of any suitable material such as a plastic material, such as PTFE, poly(methyl meth)acrylate or polyoxymethylene or a metal, preferably steel.

Preferably, if the container is a glass container, a shock absorbing pad may be arranged between the glass container and the container holder to prevent damage and seal the glass container.

In some embodiments, the membrane holder includes clamping means for mounting the membrane, the membrane holder and/or the clamping means being configured to receive membranes having different thicknesses. Typically, the clamping means may be adjustable. Examples of clamping means include screws, clamps, bolts, locks, etc.

In some embodiments, the device comprises a base, and preferably the first chamber is partially formed by the base.

In other embodiments, the base and/or the membrane holder includes at least one gasket for sealing the membrane against the base and/or against the membrane holder. The sealing ring may be configured so that it completely circumferentially surrounds the periphery of the membrane. The sealing ring may also include a gas outlet in fluid communication with the first chamber and being configured to vent any gas present in the first chamber out of the first chamber.

In some embodiments, the base and/or the membrane holder comprises a spacer ring. Such a spacer ring allows membranes of different thicknesses to be used. In some embodiments, the first chamber comprises a gas outlet, in particular a fluidic switch such as for example a valve. The gas outlet and the membrane are arranged such that the gas inside the first chamber is, upon feeding the fatty phase into the first chamber, in particular upon the first initial filling of the first chamber with the fatty phase, directed towards the gas outlet and removed from the first chamber via the gas outlet. In some examples, the membrane is inclined relative to the central longitudinal axis of the device. Thus, the angle in a sectional view along the central longitudinal axis between the central longitudinal axis and the first and/or second side of the membrane is other than 90°. For example, the acute angle between the second side of the membrane and the central longitudinal axis may be between 45° and 89°, preferably between 70° and 88°, more preferably between 78° and 87°. In such embodiments, the gas outlet may be arranged at the upper edge of the first chamber, which is formed by the membrane and another chamber wall. This ensures that any residual gas, in particular air, present in the first chamber, for example before use of the apparatus, rises towards the membrane and, due to the inclined arrangement of the membrane, is directed towards the upper edge and thus towards the gas outlet. Normally, the membrane channels are too narrow for air to pass through them and, therefore, a gas outlet as described in the above embodiments allows for the removal of all remaining gas, which would otherwise negatively influence the uniform drop size and distribution or prevent the first fluid from reaching all micro-channels, thus decreasing the flow rate. Typically, the gas outlet may be in fluid communication with the device environment.

In some embodiments, and as already described above, the device comprises at least one heater for heating the fatty phase of step a. and/or the aqueous phase of step b. and/or at least one cooler for cooling the transient dispersion of step c. It may in particular be advantageous to heat or cool one or the other of the phases, since the hardening of the generated drops can be easily carried out by temperature changes. Typically, the at least one heating element can provide sufficient thermal energy to heat the fatty phase of step a. and/or the aqueous phase of step b. up to 100°C, up to 125°C or up to 150°C. The heater may for example comprise a heating bath, such as a water bath or an oil bath. Alternatively, the heater may be an IR radiator, a heating coil or any other suitable heater.

According to one embodiment, the device comprises a cooler positioned at the level of the second chamber and/or after the exit of the second chamber so as to accelerate the cooling kinetics of the drops and thus optimize their mechanical resistance, and optionally to trigger step d.

In other embodiments, the device comprises a first reservoir for the fatty phase of step a. and/or a second reservoir for the and/or aqueous phase of step b. Both the first and second reservoirs may be pressurized. For example, the reservoirs may be fluidically connected to a pressure source, such as a compressor. Alternatively, the reservoirs may be syringes and pressurized by a common syringe pump and/or a piston or peristaltic, gear, or other pumping system.

In some embodiments, a flow restrictor is arranged between the second reservoir for the aqueous phase of step b. and the second chamber. Such a restrictor is advantageous, since the second chamber generally does not provide significant flow resistance for the aqueous phase of step b. Thus, by using a flow restrictor, the device is more stable, since unintentional pressure differences, for example due to fluctuating air pressure, can be avoided.

In other embodiments, the second inlet comprises a feed channel arranged at least partially circumferentially around the central longitudinal axis, respectively the axis being perpendicular to the first and second sides of the membrane and intersecting the center of the membrane. The feed channel comprises one or more openings in the second chamber. "at least partially circumferentially arranged around the axis" mentioned above means that the feed channel may have the outline of a partial circle, such as a semicircle or a third of a circle, etc. Preferably, the feed channel is arranged entirely circumferentially around the central longitudinal axis, respectively the axis being perpendicular to the membrane and intersecting the center of the membrane. In such embodiments, the feed channel forms an annular structure. Preferably, the feed channel comprises multiple openings in the second chamber, which are in particular essentially uniformly distributed along the circumference of the feed channel. Typically, the opening(s) of the feed channel may be arranged towards the outlet of the second chamber, i.e., such that the openings face the outlet of the second chamber. Embodiments comprising a feed channel have the advantage that the aqueous phase of step b. may be uniformly and smoothly introduced into the second chamber without causing harmful turbulence that negatively influences the uniform shape and size distribution of the generated drops. In some embodiments, the opening(s) of the feed channel are arranged such that a vortex is generated when the aqueous phase of step b. is introduced into the second chamber. In particular, the opening(s) may be tubular and the longitudinal axis of each tubular opening may be inclined relative to the central longitudinal axis of the device. Typically, all tubular openings are uniformly inclined. The generation of a vortex is beneficial because the transport of the generated dispersion towards the outlet of the second chamber is accelerated, which is particularly advantageous if the density of the drops and the aqueous phase of step b. is substantially equal.

Typically, the feed channel is arranged at the bottom of the second chamber, i.e. adjacent to the membrane. The feed channel can, for example, also be arranged circumferentially around the membrane. The feed channel can have a diameter of 2 mm to 100 mm, preferably 5 mm to 20 mm.

Alternatively, the second entrance may be a single entrance opening directly into the second chamber, preferably from a lateral side of the second chamber.

In a second aspect, the overall general objective technical problem is achieved by an assembly of drops produced according to the method of any of the embodiments as described herein. Advantageously, the drops have an equal particle size distribution with a coefficient of variation less than or equal to 10%, in particular less than or equal to 8%, in particular less than or equal to 6%, in particular less than or equal to 5%, in particular less than or equal to 4%. Determining the coefficient of variation falls within the general skills of a person skilled in the art.

In certain embodiments, the drops preferably have a particle size of less than 4 mm, preferably between 100 µm and 3 mm, more preferably between 200 µm and 2 mm, in particular between 300 µm and 1 mm, and better still between 500 µm and 800 µm.

Brief description of the figures

The invention described herein will be better understood from the detailed description given below and the accompanying drawings which should not be construed as limiting the invention described in the appended claims.

The drawings show:

FIG. 1 There FIG. 1 is a schematic representation of the method according to the invention;

FIG. 2 There FIG. 2 is a schematic view of a device for generating a dispersion of a fatty phase in an aqueous phase according to a first embodiment of the invention;

FIG. 3 There FIG. 3 is a sectional view of the device shown in the FIG. 2 ;

FIG. 4 There FIG. 4 is a partially cutaway exploded view of the device shown in the FIG. 2 ;

FIG. 5 There FIG. 5 is a schematic view of a device 1 according to another embodiment of the invention;

FIG. 6 There FIG. 6 is a schematic enlarged view of a second side of a membrane according to one embodiment of the invention;

FIG. 7 There FIG. 7 is a schematic view of the device according to the FIG. 2 further comprising a stirring column after the outlet of the second chamber and adapted to ensure the performance of step d.

There FIG. 1 schematically illustrates the method according to one embodiment of the invention. The fatty phase of step a. is supplied into the first chamber 4 from the first reservoir 24 containing the fatty phase of step a. and being in fluid connection with the first chamber 4. The aqueous phase of step b. is supplied into the second chamber 5 from the second reservoir 25 containing the aqueous phase of step b. and being in fluid connection with the second chamber 5. As can be seen, the first chamber 4 and the second chamber 5 are fluidically connected by several channels 10. In the embodiment shown, the first chamber and the second chamber are separated by a membrane 7 whose first side 8 faces the first chamber and whose second side 9 faces the second chamber. The channels 10 extend from the first side 8 to the second side 9. In general, an appropriate pressure is applied to the fatty phase of step a. in the first chamber 4. The fatty phase in the first chamber 4 is then guided through the channels 10. An emulsification step takes place when the fatty phase reaches the outlet of the channel opening into the second chamber 5, thereby forming a non-suspensive transient oil-in-water dispersion (or "direct emulsion") comprising monodisperse drops of fatty phase from step a. in the aqueous phase from step b. It should be noted that the drop sizes are exaggerated for clarity. The outlet of the second chamber 6 is directly connected to a treatment pipe (or line) 37 which is configured such that the dispersion which leaves the second chamber is conveyed to a container 29, the treatment pipe 37 being in fluid communication with a third reservoir 38 adapted to ensure the injection into the treatment pipe 37 of at least one gelling inducer of the hydrophilic gelling agent, and preferably of at least one additional solution comprising the gelling inducer(s) of the hydrophilic gelling agent, whereby the final suspensive dispersion is obtained. Alternatively, an energy source 30 (not shown in FIG. 1 ) may be provided in place of the reservoir 38. For example, the energy source 30 may be a UV light source which then acts as a gelling inducer for the hydrophilic gelling agent present in the aqueous phase of the dispersion of step c., whereby a final suspensive dispersion is obtained. It is understood that in such embodiments, the processing line 37 is generally configured to be permeable to the corresponding energy used, i.e. UV light. Alternatively, the energy source 39 may be a cooler apparatus, providing thermal energy in order to activate the hydrophilic gelling agent present in the aqueous phase of the dispersion of step c., and thus to obtain a final suspensive dispersion. In the treatment line 37, the viscosity and the flow threshold of the aqueous phase of step c., in contact with the gelling inducer (or additional solution), will change, thus continuously forming a suspensive aqueous phase with respect to the drops. The final suspensive dispersion then follows the remainder of the treatment line 37 to be collected in the container 29, if necessary equipped with a stirrer (not shown). Note that the activation reaction of the hydrophilic gelling agent under the effect of the gelling inducer is initiated during the injection of the latter, if necessary in the form of an additional solution, into the aqueous phase of the dispersion of step c., the kinetics of which can last several minutes, or even several hours, and therefore continue after collection of the final suspensive dispersion in the container 29. It should also be noted that the direction of flow of the phases in FIG. 1 , carried out from top to bottom, can also be carried out in the opposite direction, and therefore from bottom to top.

There FIG. 2 represents the device 1 usable in a method according to the invention. The device 1 comprises a container 19 made of glass and the base 14 (or “base” or “base”) made of metal. The base 14 comprises a first inlet 2 (not shown, see FIG. 3 ) of fatty phase feed from step a., opening into a first chamber. The first chamber may be partially formed by the base 14 and the membrane 7 (see FIG. 3 ). The container 19 comprises a second inlet 3 for supplying the aqueous phase of step b., opening into a second chamber and a second chamber outlet 6 for collecting the dispersion generated inside the second chamber. The second chamber is formed by the container 19 and the membrane 7 (see FIG. 3 ).

There FIG. 3 shows a sectional view of device 1 of the FIG. 2 . The device 1 comprises a base 14 with a first inlet 2 for supplying the fatty phase of step a. The inlet 2 opens into the first chamber 4, which is partially formed by the base 14. The device 1 further contains a container 19 with a second inlet 3 for supplying the aqueous phase of step b. and a second chamber outlet 6 for collecting the drops in the aqueous phase of step b. The second inlet 3 opens into the second chamber 5, which is partially formed by the container 19. The first chamber and the second chamber are separated by the membrane 7. As can be seen in the FIG. 2 , the first chamber has a rounded cross-section relative to the corresponding section plane along the central longitudinal axis 15 and being perpendicular to the membrane 7. In the particular embodiment shown, the first chamber 4 has a semi-circular cross-section and can thus have the shape of a hemisphere. The first inlet 2 is arranged at the pole 13 of the hemisphere. The second chamber 5 is conical towards the outlet 6, which is arranged on the longitudinal axis 15 extending along the longitudinal direction of the device, intersecting the center of the first and second chambers, being perpendicular to the membrane 7 and intersecting the center of the membrane. As can be seen, the longitudinal axis 15 constitutes a central axis of the device in the longitudinal direction. In the embodiment shown, the second chamber is arc-shaped towards the second chamber outlet 6. Thus, the second chamber 5 has a U-shaped section. The first inlet 2 is arranged at an angle α of substantially 90° relative to the central axis 15 and to the membrane channels, which are generally parallel to the axis 15. The device 1 comprises a membrane holder 20 and a container holder 21, which are fixedly connected to each other via removable clamping means 18. The membrane 7 is mounted on the membrane holder 20 by clamping the membrane between the membrane holder 20 and the base 14. The membrane holder 20 is fixedly connected to the base 14 via clamping means 18. To securely fix a glass container 19 between the membrane holder 20 and the container holder 21, the pad 23, which in the particular case is a foam pad, can be arranged between the container 19 and the container holder 21. The membrane holder 20 comprises a groove 22 for receiving the container 19.

There FIG. 4 shows an exploded view of the device 1 partially cut from the FIG. 2 . As can be seen, the first chamber is partially formed by the base 14 and has the shape of a hemisphere. The first inlet 2, which is arranged at an angle of essentially 90° to the central axis 15, is arranged on the pole of the hemisphere. The base 14 comprises the spacer ring 16 which allows the use of different membranes of different thicknesses and the membrane holder 20 comprises the sealing ring 17. The membrane 7 is arranged between the rings 16 and 17. The design of the device 1 with adjustable clamping means 18 allows the use of membranes of different thicknesses. The membrane holder 20 further comprises a circumferential groove 22 for receiving the lower end portion of the container 19. Clamping means 18 fixedly and removably connect the membrane holder 20 to the container holder 21.

There FIG. 5 shows a schematic view of a device 1 that can be used according to a preferred embodiment of the invention. The second chamber 5 is formed by the container 19 and the membrane 7 that separates the first chamber 4 from the second chamber 5. The container 19 comprises a second chamber outlet 6, which is in fluid connection with the product container 29 and the waste container 30. In general, the fluid flow rate can be controlled by a valve, such as a three-valve valve. The device 1 further comprises a first reservoir 24 that is in fluid communication with the first chamber 4 that can either only serve as a reservoir for supplying the fat phase of step a. into the first chamber 4 via the first inlet 2, or that can also serve as a mixing container for preparing the fat phase of step a. Between the first reservoir 24 and the first inlet 2 is arranged a flow meter for measuring the fluid flow rate of the fat phase of step a. The first reservoir 24 is in fluid communication with the pressure source 32. Furthermore, the pressure regulator 27a is arranged between the first reservoir 24 and the pressure source 32. In addition to the first reservoir 24, the device 1 comprises a rinse reservoir 31 which is also in fluid communication with both the first chamber 4 and the pressure source 32. The rinse reservoir 31 is configured to supply a rinse solution into the first chamber 4 for cleaning the device 1 after its intended use. In general, if a rinse solution is supplied to the first chamber 4, the three-way valve arranged between the product container 29 and the waste container 30 and the second chamber outlet 6 is configured so that the rinse solution can flow into the waste container 30. The product container 29 can for example serve directly as a storage tank. The device 1 further comprises a heater 33 configured to heat the first and second chambers during production. In addition, the second chamber 5 is in fluid communication with the second reservoir 25 to supply the second chamber 5 with the aqueous phase of step b. The flow limiter 26 and the flow meter 28 are arranged between the second chamber 5 and the second reservoir 25. In the embodiment shown, the flow limiter 26 is arranged behind the flow meter 28 in the flow direction. The second reservoir 25 is further in fluid connection with the pressure source 32. Furthermore, the pressure regulator 27b is arranged between the second reservoir 25 and the pressure source 32. The device 1 further comprises a third reservoir 34 comprising the gelling inducer, where appropriate in the form of an additional solution, the third reservoir 34 being in fluid communication with the treatment line 37. Between the third reservoir 34 and the treatment line 37 is arranged a flow meter (not shown) to measure the flow rate of the additional solution. The third reservoir 34 is further in fluid connection with the pressure source 32.

There FIG. 6 shows a monolayer membrane 7 for generating a dispersion of a fatty phase of step a. in an aqueous phase of step b., which can be used in a method and/or device as described in any of the embodiments described herein. The membrane 7 has a first side 8 (not shown) and a second side 9 which, in an operational state, face a second chamber. Multiple microchannels 10 extend through the membrane 7. Each channel 10 has an elliptical contour. In addition, the membrane 7 comprises a membrane sealing ring 44, which fully circumferentially surrounds the periphery of the membrane.

There FIG. 7 schematically shows another embodiment of the method according to the invention. The transient dispersion is generated in the same way as in the embodiment of the FIG. 1 . In FIG. 7 , the treatment line 37 in fluid communication with the third reservoir 38 adapted to ensure the injection of the gelling inducer (or an additional solution) is coupled to a stirring column 12. Thus, the transient dispersion obtained at the outlet 6 of the second chamber 5 is moved towards the stirring column 12 via a first inlet of the lower part 20. The gelling inducer (or additional solution) is introduced from the third reservoir 38 via a second fluid inlet into the stirring column 12. This gelling inducer (or additional solution) is then physically mixed inside the stirring column 12 with the continuous aqueous phase of the transient dispersion, whereby the final suspensive dispersion is obtained. The stirring column 12 comprises a plurality of stirring rods as stirring elements. The stirring elements are each arranged longitudinally (i.e. along the longitudinal direction LO) inside the tubular column which is arranged between the head portion and the lower portion of the stirring column 12 and can each rotate about the longitudinal axis A of the tubular column. According to a particular embodiment, the stirring column 12 can also be configured to provide a simultaneous cooling or heating step. The application of heating is particularly suitable in the case where the hydrophilic gelling agent is a light-sensitive gelling agent, so as to accelerate the reaction kinetics. The application of heating can also be advantageous in the case where it is desired to manufacture drops with an alginate shell from a dispersed phase in the form of an inverse emulsion as described in WO2022106361. Indeed, such heating advantageously accelerates the destabilization of this inverse emulsion, and therefore accelerates the formation of the envelope.

The stirring column 12 further comprises an outlet which is fluidically connected to the container 29 (not shown).

The following tables illustrate 3 examples A, B and C of stable suspensive dispersions which can be manufactured with a process according to the invention as illustrated in FIG. 7 .

[Table 1]: composition of the fatty phase of step a. Raw materials INCI A / B / C % Labrafac CC Caprylic/Capric triglyceride Qsp* Nikkol Meadowfoam oil Limnanthes Alba (Meadowfoam) Seed Oil 15 EMC30 Castor Oil/IPDI Copolymer (and) Caprylic/Capric Triglyceride 33.33 Natpure Col RED LC318L Beta-Carotene (and) Helianthus Annuus (Sunflower) Seed Oil 0.012 Total 100

[Table 2]: compositions of aqueous phases from step b. Raw materials INCI HAS B C % Osmosis water Aqua Qsp* Microcare PE Phenoxyethanol 0.89 Microcare Emollient PTG Pentylene Glycol 2.22 Glycerin 4811 Glycerin 2.22 Zemea Select Propanediol Propanediol 3.22 EDETA BD Disodium EDTA 0.044 Butylene glycol 1.3 Butylene glycol 2.56 Carbopol Ultrez 10 Carbomer 0.28 0 0 Satiagel VPC 508 P Carrageenan (and) Chondrus Crispus Extract 0 0.4 0 KELCOGEL CG-LA Gellan gum 0 0 0.21 Total 100 100 100

[Table 3]: composition of additional solutions implemented in step d. Raw materials INCI HAS B C % Osmosis water Aqua Qsp* NaOH Sodium Hydroxide 0.34 0 0 Sodium chloride SODIUM CHLORIDE 0 10 2 Total 100 100 100

The preparation of the fatty phase, the aqueous phases and the additional solutions falls within the general knowledge of a person skilled in the art.

For the manufacturing process according to the invention, the injection flow rates of the different phases are as follows:

[Table 4]: Phase Flow rate (in ml/hr/channel) Aqueous phase in second chamber 120 Fat phase in first chamber 16.28 Additional solution in stirred column 14.28

This easily and continuously produces a composition in the form of a dispersion comprising a fatty phase dispersed in the form of drops with a size of 550 microns perfectly suspended in a transparent and viscous continuous aqueous phase.

This suspension is stable and lasts at least 6 months at room temperature and at least 1 month at 40°C.

Claims (16)

Process for manufacturing a dispersion comprising drops of fatty phase suspended in a continuous aqueous phase, the process comprising at least the steps of:
a. providing in a first chamber at least one fatty phase in liquid form, the fatty phase comprising at least one oil and optionally at least one lipophilic gelling agent;
b. providing in a second chamber at least one aqueous phase in liquid form, the aqueous phase comprising water and at least one hydrophilic gelling agent;
the first chamber and the second chamber being fluidically connected by one or more channels, preferably by micro-channels;
c. guiding the fatty phase of step a. from the first chamber through the channel(s) into the second chamber; and
d. exposing the aqueous phase of the dispersion of step c. to at least one gelling inducer of the hydrophilic gelling agent, whereby a dispersion comprising drops of fatty phase suspended in the continuous aqueous phase is obtained. Method according to claim 1, in which the drops comprise a core formed of at least the fatty phase and a shell. Method according to claim 1 or 2, in which the fatty phase comprises at least one lipophilic gelling agent chosen from organic or mineral, polymeric or molecular lipophilic gelling agents; fatty substances which are solid at room temperature and pressure; and mixtures thereof. Process according to any one of the preceding claims, in which the fatty phase comprises between 0.5% and 30%, preferably 1% and 25%, in particular 1.5% and 20%, better still 2% and 15%, and very particularly 5% and 12%, by weight of lipophilic gelling agent(s) relative to the total weight of the fatty phase. Process according to any one of the preceding claims, in which the aqueous phase comprises at least one hydrophilic gelling agent chosen from:
- an ion-sensitive gelling agent, in which case the gelling-inducing agent is at least one salt;
- a pH-sensitive gelling agent, in which case the gelling-inducing agent is at least one base, preferably an alkali hydroxide, and better still sodium hydroxide;
- a heat-sensitive gelling agent, in which case the gelling-inducing agent is at least one temperature lowering agent; and/or
- a light-sensitive gelling agent, in which case the gelling-inducing agent is at least light, in particular visible or UV light; and
- their mixtures. Process according to any one of the preceding claims, in which the aqueous phase comprises between 0.01% and 5%, preferably between 0.05% and 2.5%, better still between 0.05% and 1%, and most particularly between 0.08% and 0.5%, by weight of hydrophilic gelling agent(s) relative to the total weight of the aqueous phase. Method according to any one of the preceding claims, wherein step d. of exposing the aqueous phase to at least one gelling inducer of the hydrophilic gelling agent is carried out in the second chamber and/or after leaving the second chamber, preferably after leaving the second chamber. Method according to any one of the preceding claims, in which step d. consists of injecting into the aqueous phase at least one additional solution comprising at least water and at least one gelling inducer. Method according to the preceding claim, in which the additional solution comprises between 0.01% and 30%, preferably between 0.1% and 20%, better still between 1% and 15%, and very particularly between 2% and 10%, by weight of gelling inducer(s) relative to the total weight of the additional solution. Process according to any one of the preceding claims, in which the aqueous phase obtained at the end of step d. has a flow threshold greater than 0.1 Pa, in particular greater than 1 Pa, and preferably between 0.5 Pa and 100 Pa, in particular between 1 Pa and 75 Pa, very particularly between 2 Pa and 50 Pa, or even between 5 Pa and 25 Pa, and better still between 10 Pa and 20 Pa. A method according to any preceding claim, wherein the fatty phase comprises at least one, preferably a single, internal drop of an internal phase immiscible with the fatty phase. Method according to the preceding claim, in which step d. comprises stirring, preferably the stirring is carried out with a stirrer with stirring from 10 rpm to 800 rpm, preferably from 25 rpm to 500 rpm, in particular from 50 rpm to 350 rpm, and better still at 100 rpm to 150 rpm. A method according to any preceding claim, wherein the pressure applied to the first chamber is lower than the pressure applied to the second chamber, and preferably:
- a pressure of 1.01 bar to 1.15 bar, preferably 1.03 bar to 1.07 bar, is applied to the first chamber; and/or
- a pressure of 1.02 bar to 1.2 bar, preferably 1.05 bar to 1.1 bar, is applied to the second chamber. A method according to any preceding claim, wherein after step d., the formed drops are isolated, hardened and/or stored. Method according to any one of the preceding claims, in which the drops of the dispersion of step d. have an average diameter of between 150 μm and 3,000 μm, preferably between 250 μm and 2,000 μm, in particular between 500 μm and 1,500 μm, and better still between 750 μm and 1,000 μm, preferably with a coefficient of variation of less than or equal to 10%, preferably less than or equal to 5%, and better still less than or equal to 3%. Composition, in particular cosmetic, comprising at least one dispersion produced according to the process according to any one of claims 1 to 15, optionally in association with a physiologically acceptable medium.