FR2972371A1 - Forming drops of first phase dispersed in second phase, comprises providing first fluid comprising first polymer precursor, forming drops of first fluid into second fluid, supplying second polymer precursor and creating coacervate layer - Google Patents

Abstract

Forming drops (12) of a first phase (14) dispersed in a second phase (16) substantially immiscible with the first phase, comprises providing a first fluid (36) comprising the first phase and a first polymer precursor of the coacervate content in the first phase; forming drops of the first fluid into a second fluid (40) for forming the second phase; supplying a second polymer precursor of the coacervate in the second fluid; and creating the coacervate layer by interaction between the first polymer precursor and the second polymer precursor. Forming drops (12) of a first phase (14) dispersed in a second phase (16) substantially immiscible with the first phase, where each droplet has a core (17) formed of the first phase and a shell (18) formed of a coacervate layer interposed between the first phase and the second phase, comprises providing a first fluid (36) comprising the first phase and a first polymer precursor of the coacervate content in the first phase; forming drops of the first fluid into a second fluid (40) for forming the second phase; supplying a second polymer precursor of the coacervate in the second fluid; and during the formation of each droplet, or once each drop formed, creating the coacervate layer by interaction between the first polymer precursor and the second polymer precursor at the interface between the first phase and the second phase. An independent claim is included for a dispersion of drops of the first phase in the second phase substantially immiscible with the first phase obtainable by the above process.

Description

The present invention relates to a method for forming droplets of a first phase dispersed in a second phase that is substantially immiscible with the first phase, each droplet or droplet being dispersed in a second phase that is substantially immiscible with the first phase. having a first-phase core and a bark formed of a coacervate layer interposed between the first phase and the second phase, the method comprising the steps of: - providing a first fluid comprising the first phase and a first precursor polymer the coacervate contained in the first phase; - Formation of drops of first fluid in a second fluid for forming the second phase. Such a process is intended for example to form a dispersion of water-in-oil type comprising stable drops of dispersed phase, of size greater than 500 microns, and especially between 500 microns and 2500 microns, preferably between 700 microns and 1500 microns. microns. The dispersed phase is intended to contain, for example, a cosmetic product, a biologically active product, or an edible product suitable for consumption. WO 03/002248 discloses a method of the aforementioned type for dispersing in the form of drops detergent in an oily phase. The bark of the drops is formed by a coacervate of polymers. In this regard, a first precursor of the coacervate, formed by melamine, is mixed with a second precursor of the coacervate, formed by formaldehyde. These polymers are placed in an aqueous solution containing the detergent. A coacervation catalyst consisting of citric acid is also added to the aqueous phase. This aqueous phase is then dispersed in an oily solvent in the presence of an amphiphatic stabilizing polymer. Then, the dispersion is heated to a relatively high temperature to cause interphase coacervate formation by phase separation and polymerization. Such a method is not entirely satisfactory. Indeed, although the presence of the stabilizer in the oily phase limits the formation of gel in this phase, the presence of the coacervation precursors in the aqueous phase does not guarantee their proper placement at the interphase between the aqueous phase and the oily phase , when the polymerization is started.

As a result, the bark formed does not always ensure satisfactory retention of the dispersed phase and can sometimes have a large thickness. An object of the invention is to provide a method of forming a plurality of drops of a first phase, dispersed in a second phase, which makes it possible to obtain very stable drops stabilized by a very thin bark. Another object of the invention is to obtain a method of manufacturing a stable dispersion of first phase drops in a second phase which can be very concentrated, while remaining able to flow, especially at low shear. For this purpose, the subject of the invention is a process of the aforementioned type, characterized in that it comprises the following steps: feeding a second precursor polymer of the coacervate into the second fluid; during the formation of each drop, or once each drop formed, creation of the coacervate layer by interaction between the first precursor polymer and the second precursor polymer at the interface between the first phase and the second phase. The process according to the invention may comprise one or more of the following characteristics, taken alone or in any technically possible combination: the drop-forming step comprises the formation of drops of the first fluid at the outlet of a first conduit opening into the second fluid. the second phase is put into circulation in a second duct, the outlet of the first duct opening into the second duct, advantageously coaxially with the local axis of the second duct. the drops of the first phase have a diameter greater than 500 microns, advantageously less than 3000 microns, in particular between 800 microns and 2000 microns. - The supply of the second precursor polymer in the second fluid is performed after the formation of the or each drop, preferably in a reaction fluid miscible with the second fluid. the method comprises feeding into the second fluid a reaction agent capable of generating the interaction between the first precursor polymer and the second precursor polymer to form the bark after the formation of each drop. the interaction between the first precursor polymer of the coacervate and the second precursor polymer of the coacervate to form the bark is an ionic interaction. the first precursor of the coacervate is a first polymer capable of being ionized to present a first charge, the second precursor of the coacervate being a second polymer capable of being ionized to present a second charge opposite to the first charge. one of the first precursor and the second precursor is a lipophilic polymer that can be ionized in contact with an aqueous phase, for example a polymer containing a silicone and containing a functional group that can be ionized, the lipophilic polymer being advantageously a derivative of dimethicone, such as amodimethicone and its derivatives. the lipophilic polymer is a cationic lipophilic polymer such as a polymer having a primary, secondary or tertiary amine function, or such as a silicone polymer having amine functional groups, chitosan, polylysine or polyetherimine or else is a lipophilic polymer anionic, such as a polymer having a carboxylic acid function such as polyacrylic acid, or having an acrylic acid function, a methacrylic acid function or a maleic acid function. the other of the first precursor polymer and the second precursor polymer is a hydrophilic polymer capable of being ionized. the other of the first precursor and of the second precursor is a hydrophilic acrylic polymer such as a copolymer of acrylic acid or of maleic acid and of at least one other monomer, such as acrylamide or alkyl acrylates; C5-C8 alkyl acrylates, C10-C30 alkyl acrylates, C12-C22 alkyl methacrylates, methoxypolyethylene glycol methacrylates, hydroxyester acrylates - the first phase is aqueous and the second phase is oily. the drop forming step comprises feeding a continuous volume of first fluid and a continuous volume of second fluid, and then stirring the first fluid and the second fluid to form a dispersion of the first phase in the second phase. the step of feeding the second precursor polymer comprises the addition of a fluid containing the second precursor polymer in the second fluid, and the stirring of this fluid containing the second precursor polymer to disperse it in the second phase containing the drops of first phase. the bark has a thickness of less than 1 μm, in particular less than 100 nm, advantageously less than 50 nm, in particular less than 10 nm. the bark has a thickness of between 1 nm and 500 nm.

The invention also relates to a dispersion of drops of a first phase in a second phase substantially immiscible with the first phase, obtainable by a method as defined above. The invention will be better understood on reading the description which follows, given solely by way of example, and with reference to the appended drawings, in which: FIG. 1 is a diagrammatic side view of a first dispersion according to the invention, contained in a container; - Figure 2 is an enlarged view of a first-phase drop contained in the second phase and having a coacervate bark, the drop having been obtained by a first method according to the invention; FIG. 3 is a schematic side view of a first device for implementing the method according to the invention, during the implementation of this method; FIG. 4 is an enlarged view of the drop forming nozzle of the first device according to the invention; - Figure 5 is a view similar to Figure 4 of a nozzle variant; and FIG. 6 is a schematic view illustrating the different steps of a second forming method according to the invention. Figures 1 to 4 illustrate the implementation of a first method of forming drops according to the invention. Referring to Figure 1, this first method is intended to form a dispersion of drops 12 of a first phase 14 dispersed in a second phase 16 substantially immiscible with the first phase 14. In this example, the first phase 14 is by example an aqueous phase. In particular, it contains in liquid form a first product which is chosen from a biologically active product, a cosmetic product, or an edible product suitable for consumption. When the first product is a biologically active product, it is advantageously chosen from anticoagulants, anti-thrombogenic agents, anti-mitotic agents, anti-proliferation, anti-adhesion, anti-migration agents, cell adhesion promoters, the factors growth, antiparasitic molecules, anti-inflammatories, angiogenics, angiogenesis inhibitors, vitamins, hormones, proteins, antifungals, antimicrobial molecules, antiseptics or antibiotics.

Alternatively, the first phase 14 contains reagents such as proteins or reagents to form a bioreactor, or to form artificial cells for implants. A cosmetic product that can be contained in the heart is for example cited in the Council Directive 93/35 / EEC dated June 14, 1993. This product is for example a cream, an emulsion, a lotion, a gel and an oil for the skin (hands, face, feet, etc.), a foundation (liquid, paste) a preparation for baths and showers (salts, mousses, oils, gels, etc.), a hair care product (hair dyes and bleaches ), a cleaning product (lotions, powders, shampoos), a hair care product (lotions, creams, oils), a styling product (lotions, lacquers, glossines), a product for shaving (soaps, mousses, lotions, etc.), a product intended to be applied to the lips, a sun product, a sunless tanning product, a product for whitening the skin, an anti-wrinkle product. The edible products that are suitable for consumption by a human being or an animal are advantageously purees of vegetables or fruits such as mashed mango, pear puree, coconut puree, onion cream, leeks, carrots, or other preparations that can mix several fruits or vegetables. Alternatively, it is oils such as a food oil, such as olive oil, soybean oil, grape seed oil, sunflower oil, or any other oil extracted from the plants. The second phase 16 is advantageously an oil. This phase is carried out for example from a liquid oil with a viscosity of less than 20000mPa / s. preferably below 1000mPa / s. The oil constituting the oily phase is, for example, a silicone oil, a mineral oil, a vegetable oil or a mixture of these oils. The second oily phase comprises, in a variant, molecules of cosmetic interest, such as active agents, dyes, stabilizers, preservatives, modifying agents chosen from agents of texture, viscosity, pH, strength osmotic or refractive index modifiers.

Advantageously, the dispersion 10 is substantially translucent. By substantially translucent is meant that the absorbance of the dispersion according to the invention is generally less than 5%, preferably less than 20/0, preferably less than 10/0 for at least one wavelength in the visible spectrum included from 400 nanometers to 1000 nanometers, advantageously over any wavelength of the visible spectrum from 400 nanometers to 1000 nanometers.

The intensity transmitted through the dispersion 10 according to the invention is divided by a factor of at least 103 in comparison with a conventional concentrated emission. This translucency is measured by introducing a dispersion sample into a vessel of 2 mm optical path at wavelength between 400 nanometers and 1000 nanometers. The first phase 14 and the second phase 16 are substantially immiscible. Thus, the solubility of the first phase 14 in the second phase 16 is advantageously less than 5% by weight. The method according to the invention makes it possible to obtain a plurality of drops 12 of first phase 14 as illustrated in FIG. 2. Each drop 12 thus comprises a core 17 consisting of first phase 14 and a bark 18 for retaining and stabilizing heart 17, the bark 18 being formed by a coacervate between a first precursor polymer and a second precursor polymer, as described in detail below. In the example shown in FIG. 1, each drop 12 has a density greater than that of the second phase 16 in which it is dispersed. Thus, the drops 12 accumulate at the bottom of the container 20 which receives the dispersion 10. The drops 12 are arranged in abutment on each other. As a result, the dispersion comprises at least one concentrated region 22 comprising drops 12 and at least one drop-free region 12 and comprising exclusively second phase 16. In the example represented in FIG. 1, the concentration of drops in the concentrated region 22 is high, so that the first phase volume content in the concentrated region 22 is greater than 50% and in particular is greater than 60%. In this example, the diameter of the drops 12 is greater than 500 microns, and is advantageously less than 3000 microns. Advantageously, the diameter of the drops is between 500 microns and 2500 microns. The drops 12 are visible in the aqueous phase 16. In one embodiment, when the drops of the dispersion have a size greater than 500 microns, the invention proposes to provide a dispersion of water-in-oil type whose drops 12 exhibit uniform size distribution. More precisely, according to this mode, the dispersed aqueous phase consists of a population of monodisperse drops such that they have a mean diameter D of between 500 μm and 3000 μm and a coefficient of variation Cv of less than 10%. In the context of the present description, the term "monodisperse drops" means that the population of dispersed drops of the dispersion according to the invention has a uniform size distribution. Monodisperse drops have good monodispersity. Conversely, drops with poor monodispersity are called "polydisperse".

The average diameter D of the drops is for example measured by analysis of a photograph of a batch consisting of N drops, by an image processing software (Image J). Typically, according to this method, the diameter is measured in pixels, then reported in microns, depending on the size of the container containing the drops dispersion. Preferably, the value of N is chosen greater than or equal to 30, so that this analysis reflects in a statistically significant manner the drop diameter distribution of said emulsion.

The diameter Di of each drop is measured, then the average diameter D is obtained by calculating the arithmetic mean of these values Di: _ ND ^ 1 E Di N iol From these values Di, one can also obtain the standard deviation D Dispersion droplet diameters: The standard deviation D of a dispersion reflects the distribution of the diameters Di of the drops of the dispersion around the average diameter D. Knowing the average diameter D and the standard deviation D of a dispersion, it can be determined that 95% of the droplet population is in the range of diameters D 23; D ^ 23_ and that 680/0 of the population is found in the interval D ^ O; To characterize the monodispersity of the dispersion according to this mode of the invention, the coefficient of variation Cv: C ^ G D can be calculated. This parameter reflects the distribution of the diameters of the drops as a function of the average diameter thereof.

The coefficient of variation of the diameters of the drops of the dispersion according to this embodiment of the invention is less than 10%, preferably less than 5%.

Alternatively, the monodispersity can be demonstrated by placing a dispersion sample in a vial of constant circular section. A gentle stirring by rotating a quarter of a turn for half a second about the axis of symmetry passing through the vial, followed by a rest of half a second is performed, before repeating the operation in the opposite direction. , and this four times in a row. The drops 12 of the dispersion are organized in a crystalline form when they are monodisperse. Thus, they have a stack in a repeating pattern following in three dimensions. It is then possible to observe, a regular stack which indicates a good monodispersity, an irregular stack reflecting the polydispersity of the dispersion. When the dispersion is left to stand, the drops 12 are stable and do not adhere to each other, no coalescence is observed after 2 weeks at 40 ° C. The dispersion according to the invention supports stirring without shear without undergoing significant coalescence of the drops 12 or an alteration of its monodispersity. To test this property, a sample of the dispersion according to the invention is placed in a 2 ml container, and then it is placed in a cell of a stirring plate (IKA vortex Genius 3). The size of a cell is about 50% larger than that of the container containing the sample. Thus, during agitation the container hits the walls of the cell, which creates a large number of shocks. The stirring speed is about 500 rpm. The test is considered successful when less than 50% of drops in number have coalesced after one hour of stirring without shearing.

In addition to the properties stated above, such drops are non-elastic, and exhibit granular behavior when the emulsion is agitated, so that they flow over each other such solid objects and they adopt a particulate behavior in suspension. In addition, the dispersion according to the invention may have the following properties.

According to some advantageous embodiments, the dispersion according to the invention supports a fall of a height of one meter without undergoing significant coalescence of the drops, nor an alteration of its monodispersity. To test this property, a sample of the dispersion according to the invention is placed in a 2 ml container, and then it is dropped at the top of a one meter high glass tube serving as a guide, on a substrate. solid, and recovered at its lower end. The operation is repeated three times. The test is considered successful when less than 50/0 of drops 12 in number have coalesced after the three falls. The drops 12 are substantially inelastic. The non-elasticity of the drops may be characterized by a very low resistance to flow threshold, measured for example by the following method: a dispersion sample 10 is placed in a rheometer of the RFSII rheometrics type using a cone-plane geometry having a gap of 45 micrometers. The shears studied are weak, and are in particular between 1% and 10%. The shear modulus is measured for increasing shear between 1 s -1 and 10 s -1.

Thus, the shear modulus, under low shear, especially equal to 2 s -1, is less than 200 Pa.s, and is especially less than 100 Pa.s. This shear modulus is at least 104 less than the shear modulus observed at the same shear, for a conventional dispersion stabilized by surfactants and having the same composition in 1000 and in water.

In comparison with a conventional 80% concentrated monodisperse emulsion (oil / water) (see Mason et al J. Coll Int Sci 179, 439-448 (1996)), a concentrated emulsion according to this present embodiment a viscosity η (Pa.s) lower by a factor of 104, for a shear of from 1 to 12 s -1. The heart 17, even surrounded by the bark 18, is substantially liquid or slightly gelled.

With the method according to the invention, the drops 12 obtained by this process have a very thin bark 18, in particular of thickness less than 1% of the diameter of the drops 12. The thickness of the bark 18 is thus less than 1 μm and is too small to be measured by optical methods. This size is generally between 1 nm and 500 nm, preferably less than 100 nm, advantageously less than 50 nm, preferably less than 10 nm. The measurement of the thickness of the bark of the drops of the invention can be carried out by the small angle neutron scattering (Small-Angle X-ray Scattering) method, as implemented in Sato et al. J. Chem. Phys. 111, 1393-1401 (2007).

For this purpose, the drops are produced using deuterated water, and are then washed three times with a deuterated oil, such as, for example, a deuterated hydrocarbon-type oil (octane, dodecane, hexadecane). After washing, the drops are then transferred to the Neutrons cell to determine the I (q) spectrum; q being the wave vector.

From this spectrum, classical analytical treatments (REF) are applied to determine the thickness of the hydrogenated (undeuterated) bark. The bark 18 surrounding the drops of the emulsion according to the invention is stiffened, which has the advantage of conferring superior resistance to the drops and to reduce or prevent their coalescence.

This bark is typically formed by coacervation, i.e. precipitation of charged polymers of opposite charges. Within a coacervate, the bonds binding the charged polymers to each other are of ionic type, and are generally stronger than electrostatic type bonds present within a surfactant-type membrane. The bark 18 is formed by coacervation of at least two charged polymers of opposite polarity (or polyelectrolyte) and preferably in the presence of a first polymer, anionic type, and a second polymer, different from the first polymer, from cationic type. In the context of the present description, the term "anionic polymer" means a polymer having anionic type chemical functions. We can also speak of anionic polyelectrolyte. By "anionic chemical function" is meant a chemical function AH capable of giving a proton to give an A- function. Depending on the conditions of the medium in which it is located, the anionic type polymer therefore has chemical functions in AH form, or in the form of its conjugate base A-.

As an example of chemical functions of anionic type, mention may be made of the carboxylic acid functions -OOOH, optionally present in the form of carboxylate anion -COO-. As an example of anionic type polymer, there may be mentioned any polymer formed by the polymerization of monomers at least a part of which carries anionic type chemical functions, such as carboxylic acid functions. Such monomers are, for example, acrylic acid, maleic acid, or any ethylenically unsaturated monomer containing at least one carboxylic acid function. Examples of anionic polymer suitable for carrying out the invention include copolymers of acrylic acid or maleic acid and other monomers, such as acrylamide, alkyl acrylates and the like. C5-C8 alkyl acrylates, C10-C30 alkyl acrylates, C12-C22 alkyl methacrylates, methoxypolyethylene glycol methacrylates, hydroxyester acrylates. In the context of the present description, the term "cationic polymer" means a polymer having chemical functions of cationic type. We can also speak of cationic polyelectrolyte. By "chemical function of cationic type" is meant a chemical function B capable of capturing a proton to give a function BH +. Depending on the conditions of the medium in which it is located, the cationic type polymer therefore has chemical functions in B form, or in BH + form, its conjugated acid.

As an example of chemical functions of cationic type, mention may be made of the primary, secondary and tertiary amine functions, optionally present in the form of ammonium cations. As an example of a cationic type polymer, there may be mentioned any polymer formed by the polymerization of monomers, at least a part of which carries chemical functions of cationic type, such as primary, secondary or tertiary amine functions. Such monomers are, for example, aziridine, or any ethylenically unsaturated monomer containing at least one primary, secondary or tertiary amine function. Among the examples of cationic polymer suitable for the implementation of the invention, there may be mentioned amodimethicone, derived from a silicone polymer (polydimethylsiloxane, also called dimethicone), modified by primary amine and secondary amine functions: x HY HO Amodimethicone Mention may also be made of amodimethicone derivatives, for example copolymers of amodimethicone, aminopropyl dimethicone, and more generally silicone polymers containing amine functions.

Mention may be made of PEG-14 / amodimethicone bis-isobutyl copolymer and bishydroxy / methoxy amodimethicone. Mention may also be made of polysaccharide polymers comprising amine functions, such as chitosan. Mention may also be made of polypeptide polymers comprising amine functions, such as polylysine. Mention may also be made of polyethyleneimine polymers comprising amine functions, such as linear or branched polyethyleneimine. Coacervation generally takes place in the presence of a first anionic type polymer and a second cationic type polymer, which act as membrane stiffening agents.

The formation of the coacervate between these two polymers is generally caused by a modification of the conditions of the reaction medium (temperature, pH, reagent concentration, etc.). The coacervation reaction results from the neutralization of these two charged polymers of opposite polarities and allows the formation of a membrane structure by electrostatic interactions between the first and second polymers. The membrane thus formed around each drop completely encapsulates the core 17 and isolates the first phase 14 of the second phase 16. As will be seen below in the description of the process according to the invention, the first polymer is initially contained in the one of the first phase 14 and the second phase 16, the second polymer being initially contained, before the formation of the drops 12, in the other of the first phase 14 and the second phase 16. The two polymers then migrate to the interface during the formation of the drops where they form the bark 18 by coacervation. An advantageous dispersion is such that each drop comprises, in mass relative to the mass of said drop: from 0.05% to 10% of a polymer P, of anionic and hydrophilic type, and from 0.05% to 10% of a polymer P2 of cationic and lipophilic type. Preferably, each drop comprises, in mass relative to the mass of said drop, from 0.1% to 5% of a polymer P, of anionic and hydrophilic type.

Preferably, each drop comprises, by weight relative to the mass of said drop, from 0.1% to 5% of a polymer P2 of cationic and lipophilic type. An advantageous dispersion according to this variant is such that each drop comprises a polymer PI, of anionic and hydrophilic type, and a polymer P2, of cationic and lipophilic type, in a weight ratio P1: P2 of between 1:10 and 10: 1.

The first method according to the invention is implemented by means of a microfluidic method in an apparatus 30 illustrated in FIGS. 3 and 4. This apparatus 30 comprises a drop-forming nozzle 32 and a receptacle 33 for receiving the drops. drops formed. The formation nozzle 32 comprises an internal conduit 34 for supplying an internal fluid 36 comprising the first phase 14, and an external conduit 38 disposed around the inner conduit 36 for delivering an external fluid 40 forming at least a part of the second In the example illustrated in FIG. 4, the nozzle 32 also advantageously comprises a conduit 42 for supplying a reaction fluid 44 opening into the external conduit 36.

The apparatus 30 further includes internal fluid supply means 36 in the inner conduit 36, external fluid supply means 40 in the annular space defined between the inner conduit 34 and the outer conduit 38 and means 50 for supplying the reaction fluid 44 into the supply line 42 for the reaction fluid when it is present. In the example shown in Figures 3 and 4, the maximum diameter of the ducts 34, 38 and 42 is less than 3 mm to preserve the microfluidic nature of the process. The internal duct 34 is advantageously arranged coaxially in the outer duct 38. It is connected upstream to the supply means 46. It opens downstream through a downstream opening 52 disposed in the external duct 38, set back from the opening downstream 54 defined by the external duct 38, above this opening 54. Thus, the distance separating the downstream opening 52 of the inner duct 34 and the downstream opening 54 of the external duct 38 is preferably greater than 1 times the diameter of the external conduit 38.

The external duct 38 defines with the inner duct 34 an annular space connected upstream to the supply means 48. The downstream opening 54 of the outer duct 38 is located above and away from the container 33. It thus opens in a volume of air. The supply duct 42 opens transversely into the external duct 38, downstream of the downstream opening 52 of the internal duct 36 and upstream of the downstream opening 54 of the external duct 38. It is connected upstream to the supply means 50. The supply means 46, 48 and 50 each comprise, for example, a syringe pump, a peristaltic pump or other flow-generating pressure-generating system, such as for example a pressure vessel coupled with a flow meter and a pump. flow control system. Each of the supply means 46, 48, 50 is suitable for conveying a respective fluid 36, 40, 44 at a controlled and adjustable flow rate. The container 33 is disposed below the downstream opening 54. It contains a volume 55 of liquid intended to form another part of the second phase 16, advantageously an external fluid volume 40. The upper surface of the volume 55 of fluid is located axially away from the downstream opening 54, taken along the axis A-A ', so that the drops 12 formed in the nozzle 32 fall under the effect of their weight through a volume of air between the downstream opening 54 and the upper surface 56 of the volume 55 of liquid.

In a variant (not shown), the downstream opening 54 is immersed in the fluid volume 55.

In the example shown in FIG. 3, the device 30 has been illustrated with a single nozzle 32. In an advantageous variant, the system 30 comprises a plurality of nozzles 32 arranged in parallel above and opposite a container 33.

A first method according to the invention will now be described. Initially, the internal fluid 36 is prepared by mixing the first phase 14 for forming the core 17 of the drop 12 and the first precursor polymer of the coacervation. In this example, the internal fluid 36 is advantageously aqueous and the first polymer is a water-soluble polymer, for example of the anionic type. In parallel, the external fluid 40 is also prepared by mixing an oily solvent and optionally a stabilizing agent formed for example by a surfactant. The stabilizing agent is typically located at the interface between the oily phase and the aqueous phase, stabilizing the drops and preventing their coalescence before the formation of the bark. The stabilizing agent is for example a surfactant or a hydrophobic resin. When the stabilizing agent is a surfactant, it is for example formed by a nonionic surfactant such as a polyethylene glycol, especially a polyethylene glycol dimethicone. When the stabilizing agent is a hydrophobic resin, this resin may be, for example, a silicate, such as a trimethylsiloxysilicate resin. The mass content of stabilizing agent is for example between 100/0 and 0.001 ° / 0. In this example process, a reaction fluid 44 is also prepared. This fluid contains a second precursor polymer for coacervation, advantageously dissolved in the same oil as that present in the external fluid 40. The reaction fluid 44 further comprises a reaction agent capable of generating coacervation of the first polymer with the second polymer, such as an agent that can change the pH as an acid or a base.

In this example, the reaction agent is a base. Then, the internal fluid 36, the external fluid 40, and the reaction fluid 44 are respectively arranged in the respective feed means 46, 48 and 50. Similarly, a liquid mass 55 formed of an oily solvent of a similar nature to that of the external fluid 40 is introduced into the container 33.

Then, the supply means 46, 48 and 50 are activated.

The flow of internal fluid 36 flowing in the inner duct 34 generates droplets 12 of first phase 14 at the downstream opening 52 of the internal duct when the internal fluid 36 passes into the external fluid 40. The drops 12 then circulate in the external fluid 40 to the opening 54. They come into contact with the reaction fluid 44 introduced through the supply line 42. The first polymer present in the internal fluid 36 migrates at the interface between the internal fluid 36 and the fluid external 40. Similarly, the second polymer present in the external fluid 40 migrates at the interface between the external fluid 40 and the internal fluid 36. Under the action of the reaction agent, the coacervation between the first polymer and the second polymer occurs to form the bark 18. The first polymer and the second polymer are not present initially in the same phase, the risk that they react prematurely, especially before training drops 12 of internal fluid 36 in the external fluid 40, ensures that the bark 18 formed at the interface between the inner phase 14 and the outer phase 16 is complete, very thin, and does not cause total gelation of the heart 17. The drops 12 thus formed are very stable, little or not elastic and do not tend to coalesce on each other. At least one drop 12 formed in the outer conduit 38 is then received in an external drop 60 of external fluid 40 which is formed at the outlet of the outer conduit 38, at the downstream opening 54. The outer drop 60 falls into the volume 55 through a volume of air and drops 12 of internal phase 14 sediment in the second phase 16 formed by the external fluid 40 drops 60 and the volume 55. The method according to the invention is particularly effective in forming stable drops of dimensions greater than 500 microns, without the use of surfactants and in a particularly controlled manner. Figure 5 illustrates a nozzle 32 for an alternative drop forming apparatus 12 according to the invention. Unlike the nozzle 32 shown in FIG. 4, the external duct 38 comprises an upstream section 70 and a downstream section 72, the upstream section 70 partially projecting into the downstream section 72. The upstream section 70 has a lower cross section at the cross section of the downstream section 72. The feed duct 42 opens downstream in the annular space delimited between the upstream section 70 and the downstream section 72. Furthermore, the contour of the cross section of the upstream section 70 is not necessarily homothetic to the contour of the cross section of the downstream section.

Thus, the upstream section 70 may have a circular cross section and the downstream section a polygonal cross section, for example square or rectangle. The implementation of the method according to the invention in this variant of apparatus 30 is moreover analogous to that of the first method.

A second method according to the invention is described with reference to FIG. 6. This process is carried out batchwise in a container 20. Initially, in step (a), a first continuous volume of internal fluid 36 is disposed in the container 20. As previously described, the internal fluid 36 contains the first phase 14 and the first polymer. Then, in step (b), a second continuous volume of external fluid 40 is introduced into the container 20 above the internal fluid 36. The two volumes are then substantially separated without being significantly dispersed one inside the other. . Then, the container 20 is agitated to produce a dispersion of drops 12 of internal fluid 36 in external fluid 40 (step (c) in Figure 6). During this step, the first precursor polymer present in the internal fluid 36 migrates at the interface between the drops 12 of internal fluid 36 and the external fluid 40. Then, a determined amount of reaction fluid is added to the container 20 (step (d) in Figure 6). This reaction fluid contains the reaction agent and the second precursor polymer. Similarly, the second polymer present in the external phase 40 migrates at the interface between the drops 12 of internal fluid 36 and the external phase 40. The reaction agent then migrates at the interface between the drops of internal fluid 36 and the external fluid 40 and initiates the coacervation between the first polymer and the second polymer to form the bark 18. In order to improve this dispersion, the container 20 is stirred again (step (e)).

As described above, the first precursor polymer and the second polymer being brought into contact only after formation of the drops 12, or during this formation, the process avoids the important formation of gel in the drops 12 and allows the formation of a bark 18 of reduced size. As described above, the first polymer is disposed in a first fluid containing the first phase 14 and the second polymer is included in an immiscible fluid with the first phase. The second polymer can be added in the second fluid in which the drops 12 are formed or in a reaction fluid added optionally after the droplets 12 have been formed. Examples of implementation of the process will now be described. EXAMPLE 1 On the experimental device FIG. 3 shows a step of stiffening in line between a first polymer, of anionic and hydrophilic type (polyacrylic acid), and a second polymer of cationic and lipophilic type (amodimethicone). The first polymer is contained in the internal fluid 36 (pH between 3 and 4) and the second polymer is contained in the reaction fluid (which also contains a base), which is supplied perpendicularly to the other two via a T-connector. positioned at the end of the collection tube.

The stiffening step is based on the formation of a coacervate at the interface between the polyacrylic acid contained in the internal fluid and an amino-silicone (Amodimethicone) provided by the reaction fluid after formation of the drops. The meeting of these two polymers causes the coacervation and the stiffening of the membrane around the drops.

On this experimental device described the following flow rates are applied: FE = 6000 μUhour, FI = 4000 μUhour and FR = 2000 μUhour The composition of each fluid is described in the Table below. Phase Product name ° / 0 mass Function External fluid PDMS 6 sCt 98% Solvent DC 749 2% Stabilizing agent Internal fluid Water 99.5% Solvent Polyacrylic acid 0.5% Strengthening agent PDMS 6 sCt 96% solvent Amino reaction fluid silicone 2% stiffening agent Dibutylethanolamine 2% PDMS base 6 cSt = polydimethylsiloxane (dimethicone) with a viscosity of 6 cSt DC 749 = 50/50 mixture of cyclomethicone (cyclopentasiloxane) and trimethylsiloxysilicate A bottle containing drops is obtained after collection about 900 microns in diameter having a uniform size according to the methods described above.

The drops are stable to the shearless agitation test and the shear agitation test (less than 50% of the drops coalesce). Likewise, no coalescence is observed after 2 weeks at 40 ° C. The sample supports a drop of one meter on a solid substrate.

The drops are non-adhesive and slide over each other when the emulsion is agitated. EXAMPLE 2 This example puts forward an in-line stiffening step between a first polymer, of anionic and hydrophilic type (polyacrylic acid), and a second polymer, of cationic and lipophilic type (amodimethicone). The manufacture is carried out in the same device as that of Example 1. The stiffening step is based on the formation of a coacervate at the interface between the polyacrylic acid contained in the internal fluid and an amino- silicone provided by the reaction fluid after formation of the drops. On the experimental device described, the following flow rates are applied: FE = 13000 micro L / HR, F1 = 5000 μl / hour and FR = 1250 μl / hour. The composition of each fluid is described in the table below. Phase Product name% by weight PDMS function 6 sCt 98.5% Solvent External fluid PEG10-dimethicone 0.1% Stabilizing agent Diethylethanolamine 0.05% Base Internal fluid Water 99.5% Solvent Polyacrylic acid 0.5% Rigidifying agent Fluid PDMS 6 sCt 99% solvent Amino-silicone 1% stiffening agent Example 3 Batch rigidification device This example implements a batch stiffening step between a first polymer, of anionic and hydrophilic type of carbomer type (polyacrylic acid) and a second polymer of cationic and lipophilic type (amodimethicone). The first polymer is contained in the internal fluid (pH between 3 and 4) and the second polymer is contained in the reaction fluid (which also contains a base). The composition of each fluid is described in the Table below Phase Product name% by mass Function External Fluid PDMS 6 sCt 100% Solvent Internal Fluid Water 99.75% Carbomer solvent = 0.25% Hardening agent Polyacrylic acid Reaction fluid PDMS 6 sCt 98.8% Amino-silicone solvent 1% stiffening agent 0.2% diethylethanolamine Base In a 4 mL glass vessel, 0.8 mL of internal fluid is added followed by 2 mL of external fluid. The container is then stirred for 15 seconds at 1400 rpm on a vortex (IKA MS2 minishaker), whereby the drops of internal fluid are formed in the external fluid. In order to stiffen the formed drops, 0.2 ml of reaction fluid is then added to the container, which is then stirred again for 15 seconds at 1400 rpm on a vortex (IKA MS2 minishaker). The dispersion is then allowed to stand for 5 minutes before being used. At the end of this protocol, we obtain a container containing drops of various sizes, essentially between 500 microns and 1000 microns. The drops are stable to the shearless agitation test and the shear agitation test (less than 50% of the drops coalesce). Likewise, no coalescence is observed after 2 weeks at 40 ° C. The sample also supports a drop of one meter on a solid substrate. The drops are non-adhesive and slide over each other when the emulsion is agitated.

Claims (16)

CLAIMS1.- A method of forming drops (12) of a first phase (14) dispersed in a second phase (16) substantially immiscible with the first phase (14), each drop (12) having a core (17) formed of first phase (14) and a bark (18) formed of a coacervate layer interposed between the first phase (14) and the second phase, the method comprising the following steps: - providing a first fluid (36) comprising the first phase (14) and a first precursor polymer of the coacervate contained in the first phase (14); - forming first fluid drops (36) in a second fluid (40) for forming the second phase (16); characterized in that it comprises the following steps - feeding a second coacervate precursor polymer into the second fluid (40); during the formation of each drop (12), or once each drop (12) has been formed, creation of the coacervate layer by interaction between the first precursor polymer and the second precursor polymer at the interface between the first phase (14); ) and the second phase (16). 2. A process according to claim 1, characterized in that the step of forming drops (12) comprises the formation of drops of first fluid (36) at the outlet of a first conduit (34) opening into the second fluid (40). 3.- Method according to claim 2, characterized in that the second phase (16) is circulated in a second conduit (38), the outlet of the first conduit (34) opening into the second conduit, preferably coaxially with the local axis of the second conduit (38). 4. A process according to any one of the preceding claims, characterized in that the drops (12) of first phase (14) have a diameter greater than 500 microns, preferably less than 3000 microns, in particular between 800 microns and 2000 microns . 5.- Method according to any one of the preceding claims, characterized in that the supply of the second precursor polymer in the second fluid (40) is performed after the formation of the or each drop, preferably in a reaction fluid miscible with the second fluid (40). 6. A process according to any one of the preceding claims, characterized in that it comprises feeding into the second fluid (40) a reaction agent capable of generating the interaction between the first precursor polymer and the second precursor polymer. to form the bark (18) after the formation of each drop (12). 7. A process according to any one of the preceding claims, characterized in that the interaction between the first precursor polymer of the coacervate and the second precursor polymer of the coacervate to form the bark (18) is an ionic interaction. 8. A process according to claim 7, characterized in that the first precursor of the coacervate is a first polymer capable of being ionized to present a first charge, the second precursor of the coacervate being a second polymer capable of being ionized to present a second charge opposite the first charge. 9. A process according to claim 8, characterized in that one of the first precursor and the second precursor is a lipophilic polymer capable of being ionized in contact with an aqueous phase, for example a polymer containing a silicone and containing a functional group capable of being ionized, the lipophilic polymer being advantageously a derivative of dimethicone, such as amodimethicone and its derivatives. 10. A process according to claim 9 characterized in that the lipophilic polymer is a cationic lipophilic polymer such as a polymer having a primary, secondary or tertiary amine function, or such as a silicone polymer having amine functions, chitosan, polylysine or polyetherimine or is an anionic lipophilic polymer, such as a polymer having a carboxylic acid function such as polyacrylic acid, or having an acrylic acid function, a methacrylic acid function or a maleic acid function. 11. A process according to any one of claims 8 to 10, characterized in that the other of the first precursor polymer and the second precursor polymer is a hydrophilic polymer capable of being ionized. 12. - Method according to claim 11, characterized in that the other of the first precursor and the second precursor is a hydrophilic acrylic polymer such as copolymers of acrylic acid or maleic acid and at least one other monomer such as acrylamide, alkyl acrylates, C5-C8 alkyl acrylates, C10-C30 alkyl acrylates, C12-C22 alkyl methacrylates, methoxypolyethylene glycol methacrylates, acrylates, and the like. hydroxyester. 13. A process according to any one of the preceding claims, characterized in that the first phase is aqueous and the second phase is oily. 14.- Method according to any one of claims 4 to 13, characterized in that the drop forming step (12) comprises the supply of a continuous volume of first fluid (36) and a continuous volume second fluid (40), and then agitating the first fluid (36) and the second fluid (40) to form a dispersion of the first phase (14) in the second phase (16). 15.- Method according to claim 14, characterized in that the step of feeding the second precursor polymer comprises adding a fluid containing the second precursor polymer in the second fluid (40), and stirring this fluid of the second precursor polymer solution to disperse it in the second phase containing the first-phase drops. 16.- Dispersion of drops of a first phase (12) in a second phase (14) substantially immiscible with the first phase (12) obtainable by the method according to any one of claims 1 to 15.