WO2024003268A1 - Capsule drying method - Google Patents

Capsule drying method Download PDF

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Publication number
WO2024003268A1
WO2024003268A1 PCT/EP2023/067859 EP2023067859W WO2024003268A1 WO 2024003268 A1 WO2024003268 A1 WO 2024003268A1 EP 2023067859 W EP2023067859 W EP 2023067859W WO 2024003268 A1 WO2024003268 A1 WO 2024003268A1
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WIPO (PCT)
Prior art keywords
capsules
capsule
shell
drying
core
Prior art date
Application number
PCT/EP2023/067859
Other languages
French (fr)
Inventor
Antoine Drevelle
Wafa BOUHLEL
Edouard DULIEGE
Original Assignee
Kapsera S.A.S.
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Publication date
Application filed by Kapsera S.A.S. filed Critical Kapsera S.A.S.
Publication of WO2024003268A1 publication Critical patent/WO2024003268A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • B01J13/20—After-treatment of capsule walls, e.g. hardening
    • B01J13/206—Hardening; drying

Definitions

  • the present invention relates to a method for drying capsules having a shell formed of a gelled envelope mainly composed of biopolymer and a method for rehydrating these capsules.
  • the present invention also relates to the dehydrated capsules obtained by this drying process, and the rehydrated capsules obtained following the rehydration process.
  • the formulation in capsule form is increasingly used in a wide variety of technical fields because they provide numerous advantages. Drying these capsules could make storage and transport easier, in particular by reducing their volume and weight, but also improve the stability of the product during storage.
  • the invention here relates to a capsule drying method in which the capsule comprises a shell and a core, in which the core of the capsule is aqueous, or of the oil-in-water emulsion type, or of the water-in-oil emulsion type, in which the shell is a gelled envelope mainly composed of at least one biopolymer; in which the shell has a thickness of at least 10 ⁇ m; wherein said drying process comprises a fluidized bed drying and/or freeze-drying step.
  • the invention also relates to a dehydrated capsule capable of being obtained by the drying process according to the invention.
  • the capsules can be rehydrated, preferably before being used, especially if their effectiveness is greater in hydrated form.
  • the invention also relates to a process for rehydrating dehydrated capsules, comprising suspending the dehydrated capsules in an aqueous medium.
  • the invention relates to the rehydrated capsule capable of being obtained by the rehydration process of the invention. detailed description of the invention
  • capsule we mean here a capsule comprising at least a heart and a shell.
  • Such capsules preferably comprise a liquid core encapsulated by a substantially solid gelled envelope. This type of capsule has applications in many technical fields.
  • the shell includes one or more concentric or non-concentric compartments.
  • the capsules according to the invention comprise only one core coated by the shell.
  • the capsules according to the invention have an average diameter of less than 10 mm in hydrated form.
  • capsules are therefore very different from beads, because the beads are mainly made up of a solid or gelled matrix comprising multiple small inclusions.
  • capsules rather than beads also makes it possible to confine a greater volume of the heart.
  • the capsules have a heart volume to total capsule volume ratio greater than 20%. These capsules thus make it possible to protect a large volume of heart and therefore possibly of active agent, for a given volume of shell.
  • the capsules have, before drying, a core/shell volume ratio of between 0.2 and 3 and more preferably between 0.5 and 2.
  • the capsules are well known to those skilled in the art and can be formed by different techniques and have different shell compositions.
  • capsules used in the context of the invention are produced according to the manufacturing process described in French invention patent n°2939012.
  • the capsules according to the invention can be dehydrated. However, when they are in hydrated form, such as for example suspended in an aqueous solution, the capsules according to the invention have an average diameter of between 50 and 4000 pm, preferably between 100 and 2000 pm, more particularly between 200 and 4000 pm. 1000 pm, advantageously between 200 and 600 pm. This average diameter can be measured by various techniques well known to those skilled in the art such as particle size distribution based on laser light diffraction, fractionation by sieving or imaging by optical microscopy.
  • the capsules according to the invention additionally comprise an intermediate layer between the core and the shell. Preferably this layer is composed of at least one biopolymer in solution or hydrogel form.
  • the core of the capsules according to the invention can be aqueous, or in the form of an oil-in-water (O/W) emulsion or a water-in-oil (W/O) emulsion.
  • the core is an oil-in-water microemulsion.
  • the core of the capsules according to the invention is preferably a liquid core.
  • the viscosity of the core is less than 2000 mPa.s.
  • aqueous core we mean a core based on a predominantly aqueous phase.
  • the core of the capsule is in the form of an oil-in-water (O/W) emulsion or a water-in-oil (W/O) emulsion
  • oil or a mixture of oils can be used, preferably oils of vegetable, mineral or synthetic origin or a mixture of these.
  • oil we mean a liquid fatty substance at room temperature (25°C) and atmospheric pressure.
  • the capsules according to the invention preferably comprise at least one core encapsulated by a substantially solid gelled envelope called the shell.
  • the shell of the capsules according to the invention is mainly composed of a biopolymer having gelling properties, this biopolymer in the majority proportion in the shell is hereinafter called the main biopolymer.
  • biopolymers having gelling properties are for example alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.
  • the materials which constitute the shell are preferably biodegradable and biosourced.
  • the shell is preferably semi-permeable to gases and low molecular weight molecules.
  • the gels forming the shell can be physical or chemical, that is to say formed by coacervation or by polymerization.
  • the gelation of these biopolymers can be carried out by a variation in temperature (gellan gum), a variation in pH (chitosan, pectin) or ionic variation (alginate, carrageenan).
  • the shell of the capsules according to the invention is mainly composed of a biopolymer having gelling properties by ionic or temperature variation.
  • the shell of the capsules according to the invention is mainly composed of alginate.
  • the shell may further comprise one or more biopolymers other than the main biopolymer such as starch (in its different forms, for example amylose, pregelatinized starch), potato protein, or another biopolymer than the main biopolymer having gelling properties, such as for example alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.
  • biopolymers other than the main biopolymer such as starch (in its different forms, for example amylose, pregelatinized starch), potato protein, or another biopolymer than the main biopolymer having gelling properties, such as for example alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.
  • the shell of the capsules according to the invention comprises a gel containing water, one or more biopolymers having gelling properties, and optionally a surfactant resulting from its manufacturing process.
  • the shell of the capsules according to the invention comprises a gel containing water, alkaline alginate, and optionally a surfactant resulting from its manufacturing process.
  • the alkaline alginate is a sodium alginate or a potassium alginate.
  • Alginates are produced from brown algae called kelp, referred to by the English term “sea weed”. Such alginates advantageously have an ⁇ -L-guluronate content greater than approximately 50%, preferably greater than 55%, or even greater than 60%.
  • the surfactant is advantageously an anionic surfactant, a nonionic surfactant, a cationic surfactant or a mixture thereof.
  • the molecular mass of the surfactant is between 150 g/mol and 10,000 g/mol, advantageously between 250 g/mol and 1500 g/mol.
  • the surfactant is an anionic surfactant
  • it is for example chosen from an alkyl sulfate, an alkyl sulfonate, an alkylarylsulfonate, an alkaline alkylphosphate, a dialkylsulfosuccinate, an alkaline earth salt of saturated or unsaturated fatty acids.
  • These surfactants advantageously have at least one hydrophobic hydrocarbon chain having a number of carbons greater than 5, or even 10, and at least one hydrophilic anionic group, such as a sulfate, a sulfonate or a carboxylate linked to one end of the hydrophobic chain.
  • the surfactant is a cationic surfactant
  • it is for example chosen from an alkylpyridium or alkylammonium halide salt such as n-ethyldodecylammonium chloride or bromide, cetylammonium chloride or bromide (CTAB) .
  • CTLAB cetylammonium chloride or bromide
  • These surfactants advantageously have at least one hydrophobic hydrocarbon chain having a number of carbons greater than 5, or even 10, and at least one hydrophilic cationic group, such as a quaternary ammonium cation.
  • the surfactant is a non-ionic surfactant
  • it is for example chosen from polyoxyethylenated and/or polyoxypropylenated derivatives of fatty alcohols, fatty acids, or alkylphenols, arylphenols, or from alkyl glucosides, polysorbates, cocamides.
  • the surfactant is sodium lauryl sulfate (LSS) also called sodium dodecyl sulfate and/or polyoxyethylene sorbitan monoleate (Polysorbate 80).
  • LSS lauryl sulfate
  • Polysorbate 80 polyoxyethylene sorbitan monoleate
  • the surfactant is polyoxyethylene sorbitan monoleate (Polysorbate 80).
  • the mass content of surfactant in the shell is greater than 0.001% and is advantageously greater than 0.1%.
  • the mass concentration of surfactant is approximately 0.03%.
  • the shell may also include other compounds making it possible in particular to reinforce its resistance to drying.
  • these compounds we can cite, for example, biochar.
  • the biochar is present at a rate of 0.1 to 20% by volume fraction in the shell, advantageously from 0.5 to 15% by volume fraction in the shell, preferably from 1 to 10% by volume fraction in the shell .
  • the shell may include a sedimentation agent, that is to say an inert agent, preferably mineral, making it possible to weigh down the capsule.
  • a sedimentation agent that is to say an inert agent, preferably mineral, making it possible to weigh down the capsule.
  • a sedimentation agent according to the invention can be chosen from talc and/or silica.
  • the sedimentation agent is present at a rate of 1 to 30% by volume fraction in the shell, advantageously at a rate of 5 to 20% by volume fraction in the shell.
  • those skilled in the art are able to estimate the quantity of sedimentation agent necessary to obtain the desired effect.
  • the shell of the capsules has a thickness of at least 10 ⁇ m. Indeed, the inventors have shown that such a shell thickness gives the capsule better resistance to drying. If the shell membrane were thin, the capsule would be weakened and would not resist the shear forces/mechanical stress applied during handling of the capsules by the operator for example or the conditions of shaking of the capsules during physico-chemical treatments and there is a strong risk of breaking.
  • the shell of the capsules therefore has a thickness of between 10 pm and 1200 mm, advantageously between 20 pm and 800 pm, and more particularly between 20 pm and 400 pm.
  • the shell of the microcapsule preferably has a thickness of between 0.1% and 30%, advantageously between 1% and 20%, and more particularly between 10% and 20% of the diameter. of the capsule.
  • the invention relates to a capsule drying method in which the capsule comprises a shell and a core, in which the core of the capsule is aqueous, or of the oil-in-water emulsion type, or of the water-in-oil emulsion type, in which the shell is a gelled envelope mainly composed of at least one biopolymer; wherein said drying process comprises a fluidized bed drying and/or freeze-drying step.
  • drying on a fluidized bed we mean a process of bringing an ascending gas and a bed of particles (here the capsules) into contact, where the weight of the capsules is compensated by the current due to the flow of the gas.
  • the bed of capsules then behaves like a fluid. This technique makes it possible to increase the gas-capsule surface area to facilitate drying. Drying by fluidized bed according to the invention can be on a simple fluidized bed, vibrated fluidized bed, or fluidized bed with internal exchanger.
  • the capsules according to the invention are coated with an anti-caking agent.
  • anti-caking agent we mean an agent which limits or prevents the clumping of capsules or the formation of capsule clumps.
  • the anti-caking agents are well known to those skilled in the art and include in particular calcium carbonate, tricalcium phosphate, calcium silicate, magnesium silicate, calcium stearate, magnesium stearate, magnesium carbonate, magnesium oxide, silicon dioxide, sodium aluminosilicate, sodium ferrocyanide, potassium ferrocyanide and mixtures thereof.
  • the anti-caking agent is calcium carbonate.
  • coating here we mean the application of a layer of powder to the surface of the capsules.
  • lyophilization we mean dehydration by sublimation of water.
  • the capsules are immersed in a bath of co-formulant, then frozen at at least -80°C then freeze-dried.
  • co-formulant we mean an additional compound, without its own biological activity, serving to facilitate the handling of the capsules or to limit the degradation of the capsules.
  • cryoprotectants which can be used in the context of the invention are glycerol, poly-L-lysine, lactose, trehalose, inulin, glutamate, sodium ascorbate, magnesium sulfate, bicarbonate of sodium, sucrose, maltodextrin, milk powder and mixtures thereof.
  • the capsules are immersed in a bath of co-formulant comprising sucrose and more preferably comprising a concentration of between 50 and 500 g/L of sucrose.
  • the capsules are immersed in a bath of co-formulant comprising maltodextrin and more preferably comprising a concentration between 50 and 500g/L of maltodextrin.
  • the capsules are immersed in a bath of co-formulant comprising milk powder and more preferably comprising a concentration between 20 and 150 g/L.
  • the freezing step at -80°C is carried out until the core of the capsules is in a solid state.
  • the capsules are frozen at -80°C for at least 6 hours, and more preferably for at least 12 hours.
  • the drying process according to the invention makes it possible to obtain capsules in dehydrated form.
  • the drying process makes it possible to reduce the humidity by weight of the capsules by at least 70%, at least 80% and more particularly by at least 90%.
  • the dehydration is partial, and the capsules obtained have a humidity level of less than 10%, measured by a humidity analyzer after dehydration.
  • the invention also relates to a dehydrated capsule capable of being obtained by any of the dehydration processes of the invention.
  • the capsules obtained have a humidity level of less than 10% by weight, measured by a humidity analyzer after dehydration.
  • the average diameter of the capsule tends to decrease.
  • the capsule according to the invention has an average diameter of between 10 ⁇ m and 4 mm in dehydrated form.
  • the present invention relates to a process for rehydrating dehydrated capsules, preferably dehydrated capsules according to the invention, said process comprising suspending the dehydrated capsules in an aqueous medium.
  • the aqueous medium is composed mainly of water, preferably purified water such as ultrapure water.
  • the aqueous medium can be physiological water, that is to say purified water comprising 0.9% (m/v) sodium chloride.
  • the aqueous medium can be water supplemented with surfactant, for example with tween.
  • the rehydration process comprises suspending the dehydrated capsules in ultrapure water.
  • the rehydration process comprises suspending the dehydrated capsules in physiological water.
  • the rehydration process comprises suspending the dehydrated capsules in an aqueous medium supplemented with surfactant, preferably in physiological water supplemented with Tween.
  • the dehydrated capsules are suspended in the aqueous medium for at least 30 minutes, preferably from 30 minutes to 1 hour.
  • the dehydrated capsules are suspended at room temperature, that is to say between 10 and 25°C.
  • suspension is promoted by agitation.
  • the invention also relates to a rehydrated capsule capable of being obtained by the rehydration process of the invention.
  • the percentages are percentages by weight and the ranges of values are denoted as “between ... and ", “ranging from ... to ... ”, or “greater than...” include the specified limits.
  • the wording "comprising a” or “comprising a” means “comprising at least one” or “comprising at least” one unless otherwise specified.
  • Example 1 freeze-drying test of capsules and their rehydration
  • the first prototype includes biochar only in the core of the capsule.
  • the second prototype includes biochar in the core and shell.
  • the biochar incorporated in the capsule shell has a role here in stiffening the shell.
  • Alginate capsule prototypes are formed under the following production conditions:
  • the diameter of the injector nozzle is 200 pm.
  • the total flow rate of the core and shell fluid named Qtot is 450 mL/h, the flow ratio between the core and shell fluid, named Rq is 0.8 and gives a membrane thickness of at least 30 p.m.
  • the capsules are produced by immersion in a calcium chloride bath. A sample of the calcium chloride bath is taken for the determination of the biochar present in this bath. This is the proportion of biochar that has not been encapsulated (the encapsulation yield is slightly less than 100%). The capsules are then collected and washed with water to remove the biochar that would be deposited on the surface of the capsules.
  • a sample of wet capsules is taken for the determination of the biochar contained in the capsule.
  • the capsules are incubated in a PBS/EDTA solution to solubilize the alginate shell and thus release the contents.
  • PBS makes it possible to maintain the physiological conditions of ionic strength and pH of the solution.
  • the rest of the capsules are subsequently incubated in a co-formulant bath (SM-Sucrose, i.e. a bath comprising 300 g/L of sucrose) and frozen at -80°C.
  • S-Sucrose i.e. a bath comprising 300 g/L of sucrose
  • these capsules are freeze-dried. After freeze-drying, the capsules are washed by suspending them in an ultrapure water solution in order to allow release in the continuous phase and then to measure the biochar resulting from the rupture of the capsules during the step. freezing/lyophilization. After the washing step, a sample is taken for the determination of the biochar contained in the capsules.
  • hydrated capsules and “dehydrated capsules” include the measurement of the OD (optical density) and the estimation of the quantity of biochar found after dissolution of the capsules. This dissolution is achieved by solubilizing the alginate hydrogel which makes up the shell of the capsules.
  • a solution of PBS/EDTA phosphate buffer saline/Ethylene Diamine Tetraacetic Acid
  • EDTA makes it possible to chelate the calcium ions present in the shell.
  • the columns labeled “Calcium Bath” and “Wash Buffer” include the amount of probe lost in these baths or buffers.
  • Table 1 quantification of biochar at each stage of the treatment of prototype 1
  • the loss of biochar during the freeze-drying process is therefore estimated at only 0.5% with prototype 2.
  • the loss of biochar is therefore reduced in the presence of biochar in the shell of the capsules by a factor of 10, from 7 % to 0.5%
  • Example 2 freeze-drying test of capsules comprising a bacteriophage and their rehydration
  • Two prototype alginate capsules are tested in which bacteriophages are included in the core of the capsule and serve as a living probe in order to quantify the number of degraded capsules and/or the amount of probe lost during lyophilization and rehydration .
  • the first prototype does not include biochar.
  • the second prototype includes biochar in the hull.
  • Alginate capsule prototypes are formed under the following production conditions:
  • the total flow rate of the core and shell fluid, named Qtot, is 500 mL/h
  • the flow ratio between the core and shell fluid, named Rq is 0.8.
  • the average diameter of the two capsule prototypes is respectively 462 pm with a coefficient of variation of 17% and 542 pm with a coefficient of variation of 18%.
  • the thickness of the shell of these prototypes is at least 30 pm.
  • Bacteriophages of strain M13K07 are lytic bacteriophages that act selectively and specifically against the bacterial pathogen Escherichia coli. [Table 3] Table 3: Quantification of bacteriophages during capsule formation and drying
  • the “encapsulation yield by the so-called calcium bath method” is calculated by measuring the quantity of bacteriophage remaining in the bath and therefore not encapsulated, in relation to the quantity of bacteriophage used during the formation of the capsules.
  • Table 5 Yields of bacteriophage encapsulation
  • the loss of bacteriophage survival during freeze-drying is estimated at 5%.
  • the prototype alginate capsules are formed under the following production conditions:
  • the diameter of the injector nozzle is 150 pm.
  • the total flow rate of the core and shell fluid named Qtot is 350 mL/h, the flow ratio between the core and shell fluid, named Rq is 1, giving the capsules a membrane thickness of at least 20 p.m.
  • the capsules are mixed with calcium carbonate in 1:1 mass proportions before drying them in a fluidized air bed for 30 minutes.
  • the temperature reached within the enclosure remains below 45°C.
  • the capsules are washed by resuspension in physiological water to remove the calcium carbonate. A sample of capsules is taken to determine the bacterial concentration contained in the capsules.
  • the bacterial concentrations in the wet and dry products are 5.48.10 8 CFU/g and 4.11.10 5 CFU/g, respectively.
  • the inventors observed that the bacterial concentration of the prototype after drying in a fluidized air bed remained relatively high.

Abstract

The present invention relates to a method for drying a capsule having a shell formed by a gelled casing mainly composed of biopolymer, and a method for rehydrating said capsules. The present invention also relates to the dehydrated capsules obtained by said drying method as well as to the rehydrated capsules obtained following the rehydration method.

Description

DESCRIPTION DESCRIPTION
TITRE : Procédé de séchage de capsule TITLE: Capsule drying process
La présente invention concerne un procédé de séchage de capsules ayant une coque formée d’une enveloppe gélifiée principalement composée de biopolymère et un procédé de réhydratation de ces capsules. La présente invention concerne également les capsules déshydratées obtenues par ce procédé de séchage, et les capsules réhydratées obtenues suite au procédé de réhydratation. The present invention relates to a method for drying capsules having a shell formed of a gelled envelope mainly composed of biopolymer and a method for rehydrating these capsules. The present invention also relates to the dehydrated capsules obtained by this drying process, and the rehydrated capsules obtained following the rehydration process.
La formulation sous forme de capsule est de plus en plus utilisée dans une grande diversité de domaines techniques car elles apportent de nombreux avantages. Le séchage de ces capsules pourrait permettre d’en faciliter le stockage et le transport, notamment en diminuant le volume et le poids de celles-ci, mais aussi d’améliorer la stabilité du produit pendant son stockage. The formulation in capsule form is increasingly used in a wide variety of technical fields because they provide numerous advantages. Drying these capsules could make storage and transport easier, in particular by reducing their volume and weight, but also improve the stability of the product during storage.
L’invention porte ici sur un procédé de séchage de capsule dans lequel la capsule comprend une coque et un cœur, dans laquelle le cœur de la capsule est aqueux, ou de type émulsion huile dans eau, ou de type émulsion eau dans huile, dans laquelle la coque est une enveloppe gélifiée principalement composée d’au moins un biopolymère ; dans lequel la coque a une épaisseur d’au moins 10 pm ; dans lequel ledit procédé de séchage comprend une étape de séchage sur lit fluidisé et/ou de lyophilisation. The invention here relates to a capsule drying method in which the capsule comprises a shell and a core, in which the core of the capsule is aqueous, or of the oil-in-water emulsion type, or of the water-in-oil emulsion type, in which the shell is a gelled envelope mainly composed of at least one biopolymer; in which the shell has a thickness of at least 10 μm; wherein said drying process comprises a fluidized bed drying and/or freeze-drying step.
L’invention concerne aussi une capsule déshydratée susceptible d’être obtenue par le procédé de séchage selon l’invention. The invention also relates to a dehydrated capsule capable of being obtained by the drying process according to the invention.
Dans un second temps, les capsules peuvent être réhydratées, de préférence avant d’être utilisées, notamment si leur efficacité est supérieure sous forme hydratée. Secondly, the capsules can be rehydrated, preferably before being used, especially if their effectiveness is greater in hydrated form.
Ainsi l’invention porte également sur un procédé de réhydratation de capsules déshydratées, comprenant la mise en suspension des capsules déshydratées dans un milieu aqueux. Thus the invention also relates to a process for rehydrating dehydrated capsules, comprising suspending the dehydrated capsules in an aqueous medium.
Enfin l’invention porte sur la capsule réhydratée susceptible d’être obtenue par le procédé de réhydratation de l’invention.
Figure imgf000003_0001
détaillée de l’invention Finally, the invention relates to the rehydrated capsule capable of being obtained by the rehydration process of the invention.
Figure imgf000003_0001
detailed description of the invention
Capsule Capsule
Par « capsule », on entend ici une capsule comprenant au moins un cœur et une coque. De telles capsules, comportent de préférence un cœur liquide encapsulé par une enveloppe gélifiée sensiblement solide. Ce type de capsules présente des applications dans de nombreux domaines techniques. La coque englobe un ou plusieurs compartiments concentriques ou non. De préférence, les capsules selon l’invention ne comprennent qu’un seul cœur enrobé par la coque. De préférence, les capsules selon l’invention ont un diamètre moyen inférieur à 10 mm sous forme hydratée. By “capsule”, we mean here a capsule comprising at least a heart and a shell. Such capsules preferably comprise a liquid core encapsulated by a substantially solid gelled envelope. This type of capsule has applications in many technical fields. The shell includes one or more concentric or non-concentric compartments. Preferably, the capsules according to the invention comprise only one core coated by the shell. Preferably, the capsules according to the invention have an average diameter of less than 10 mm in hydrated form.
Ces capsules sont donc bien différentes des billes, car les billes sont principalement constituées d’une matrice solide ou gélifiée comprenant de multiples petites inclusions. These capsules are therefore very different from beads, because the beads are mainly made up of a solid or gelled matrix comprising multiple small inclusions.
L’utilisation de capsules plutôt que des billes permet en outre de confiner un plus grand volume de cœur. The use of capsules rather than beads also makes it possible to confine a greater volume of the heart.
Selon un mode préféré de l’invention, les capsules ont un ratio volume du cœur sur volume total de la capsule supérieur à 20%. Ces capsules permettent ainsi de protéger un gros volume de cœur et donc éventuellement d’agent actif, pour un volume de coque donné. According to a preferred embodiment of the invention, the capsules have a heart volume to total capsule volume ratio greater than 20%. These capsules thus make it possible to protect a large volume of heart and therefore possibly of active agent, for a given volume of shell.
De préférence les capsules ont avant le séchage un ratio volumique cœur/coque compris entre 0,2 et 3 et plus préférentiellement compris entre 0,5 et 2. Preferably the capsules have, before drying, a core/shell volume ratio of between 0.2 and 3 and more preferably between 0.5 and 2.
Les capsules sont bien connues de l’homme du métier et peuvent être formées par différentes techniques et avoir différentes compositions de coque. The capsules are well known to those skilled in the art and can be formed by different techniques and have different shell compositions.
Typiquement les capsules utilisées dans le cadre de l’invention sont produites selon le procédé de fabrication décrit dans le brevet d’invention Français n°2939012. Typically the capsules used in the context of the invention are produced according to the manufacturing process described in French invention patent n°2939012.
Comme décrit ci-après, les capsules selon l’invention peuvent être déshydratées. Cependant lorsqu’elles sont sous forme hydratée, comme par exemple en suspension dans une solution aqueuse, les capsules selon l’invention ont un diamètre moyen compris entre 50 et 4000 pm, de préférence compris entre 100 et 2000 pm, plus particulièrement entre 200 et 1000 pm, avantageusement entre 200 et 600 pm. Ce diamètre moyen peut être mesuré par diverses techniques bien connues de l’homme du métier tel que la granulométrie basée sur la diffraction de la lumière laser, le fractionnement par tamisage ou l’imagerie par microscopie optique. Dans un mode de réalisation, les capsules selon l’invention comprennent en plus une couche intermédiaire entre le cœur et la coque. De préférence cette couche est composée d’au moins un biopolymère sous forme de solution ou d’hydrogel. As described below, the capsules according to the invention can be dehydrated. However, when they are in hydrated form, such as for example suspended in an aqueous solution, the capsules according to the invention have an average diameter of between 50 and 4000 pm, preferably between 100 and 2000 pm, more particularly between 200 and 4000 pm. 1000 pm, advantageously between 200 and 600 pm. This average diameter can be measured by various techniques well known to those skilled in the art such as particle size distribution based on laser light diffraction, fractionation by sieving or imaging by optical microscopy. In one embodiment, the capsules according to the invention additionally comprise an intermediate layer between the core and the shell. Preferably this layer is composed of at least one biopolymer in solution or hydrogel form.
Le cœur The heart
Le cœur des capsules selon l’invention peut être aqueux, ou sous forme d’émulsion huile-dans-eau (H/E) ou d’émulsion eau-dans-huile (E/H). Dans un mode de réalisation de l’invention le cœur est une microémulsion huile dans eau. The core of the capsules according to the invention can be aqueous, or in the form of an oil-in-water (O/W) emulsion or a water-in-oil (W/O) emulsion. In one embodiment of the invention the core is an oil-in-water microemulsion.
Le cœur des capsules selon l’invention est de préférence un cœur liquide. De préférence la viscosité du cœur est inférieure à 2000 mPa.s. The core of the capsules according to the invention is preferably a liquid core. Preferably the viscosity of the core is less than 2000 mPa.s.
Par « cœur aqueux », on entend un cœur à base d'une phase majoritairement aqueuse. By “aqueous core”, we mean a core based on a predominantly aqueous phase.
Dans le cas, où le cœur de la capsule est sous forme d’émulsion huile-dans-eau (H/E) ou d’émulsion eau-dans-huile (E/H), l’huile ou un mélange d’huile peut être utilisé, de préférence des huiles d’origine végétale, minérale ou synthétique ou d’un mélange de celles-ci. On entend par « huile » un corps gras liquide à la température ambiante (25°C) et pression atmosphérique. In the case where the core of the capsule is in the form of an oil-in-water (O/W) emulsion or a water-in-oil (W/O) emulsion, the oil or a mixture of oils can be used, preferably oils of vegetable, mineral or synthetic origin or a mixture of these. By “oil” we mean a liquid fatty substance at room temperature (25°C) and atmospheric pressure.
La coque Shell
Les capsules selon l’invention comportent de préférence au moins un cœur encapsulé par une enveloppe gélifiée sensiblement solide appelée la coque. The capsules according to the invention preferably comprise at least one core encapsulated by a substantially solid gelled envelope called the shell.
De préférence, la coque des capsules selon l’invention est principalement composée d’un biopolymère ayant des propriétés gélifiantes, ce biopolymère en proportion majoritaire dans la coque est ci-après nommé biopolymère principal. De tels biopolymères ayant des propriétés gélifiantes sont par exemple l’alginate, la gomme de gellane, la gomme de xanthane, la pectine, le chitosan, l’agar ou le carraghénane. Preferably, the shell of the capsules according to the invention is mainly composed of a biopolymer having gelling properties, this biopolymer in the majority proportion in the shell is hereinafter called the main biopolymer. Such biopolymers having gelling properties are for example alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.
Les matériaux qui constituent la coque sont de préférence biodégradables et biosourcés. La coque est de préférence semi-perméable aux gaz et aux molécules de faible poids moléculaire. The materials which constitute the shell are preferably biodegradable and biosourced. The shell is preferably semi-permeable to gases and low molecular weight molecules.
Les gels formant la coque peuvent être physiques ou chimiques, c’est-à-dire formés par coacervation ou par polymérisation. The gels forming the shell can be physical or chemical, that is to say formed by coacervation or by polymerization.
La gélification de ces biopolymères peut être réalisée par une variation de la température (la gomme de gellane), une variation de pH (le chitosan, la pectine) ou ionique (l’alginate, le carraghénane). De préférence, la coque des capsules selon l’invention est principalement composée d’un biopolymère ayant des propriétés gélifiantes par variation ionique ou de température. The gelation of these biopolymers can be carried out by a variation in temperature (gellan gum), a variation in pH (chitosan, pectin) or ionic variation (alginate, carrageenan). Preferably, the shell of the capsules according to the invention is mainly composed of a biopolymer having gelling properties by ionic or temperature variation.
De préférence, la coque des capsules selon l’invention est principalement composée d’alginate. Preferably, the shell of the capsules according to the invention is mainly composed of alginate.
La coque peut comprendre en outre un ou plusieurs autres biopolymères que le biopolymère principal comme l’amidon (sous ses différentes formes, par exemple l’amylose, l’amidon prégélatinisé), la protéine de pomme de terre, ou un autre biopolymère que le biopolymère principal ayant des propriétés gélifiantes, comme par exemple l’alginate, la gomme de gellane, la gomme de xanthane, la pectine, le chitosan, l’agar ou le carraghénane. The shell may further comprise one or more biopolymers other than the main biopolymer such as starch (in its different forms, for example amylose, pregelatinized starch), potato protein, or another biopolymer than the main biopolymer having gelling properties, such as for example alginate, gellan gum, xanthan gum, pectin, chitosan, agar or carrageenan.
De préférence, la coque des capsules selon l'invention comprend un gel contenant de l'eau, un ou plusieurs biopolymères ayant des propriétés gélifiantes, et éventuellement un agent tensioactif résultant de son procédé de fabrication. Preferably, the shell of the capsules according to the invention comprises a gel containing water, one or more biopolymers having gelling properties, and optionally a surfactant resulting from its manufacturing process.
De préférence, la coque des capsules selon l'invention comprend un gel contenant de l'eau, de l’alginate alcalin, et éventuellement un agent tensioactif résultant de son procédé de fabrication. Preferably, the shell of the capsules according to the invention comprises a gel containing water, alkaline alginate, and optionally a surfactant resulting from its manufacturing process.
Préférentiellement l’alginate alcalin est un alginate de sodium ou un alginate de potassium. Les alginates sont produits à partir d'algues brunes appelées laminaires, désignées par le terme anglais « sea weed ». De tels alginates présentent avantageusement une teneur en a-L-guluronate supérieure à environ 50%, de préférence supérieure à 55%, voire supérieure à 60%. Preferably the alkaline alginate is a sodium alginate or a potassium alginate. Alginates are produced from brown algae called kelp, referred to by the English term “sea weed”. Such alginates advantageously have an α-L-guluronate content greater than approximately 50%, preferably greater than 55%, or even greater than 60%.
L'agent tensioactif est avantageusement un tensioactif anionique, un tensioactif non ionique, un tensioactif cationique ou un mélange de ceux-ci. La masse moléculaire de l'agent tensioactif est comprise entre 150 g/mol et 10000 g/mol, avantageusement entre 250 g/mol et 1500 g/mol. The surfactant is advantageously an anionic surfactant, a nonionic surfactant, a cationic surfactant or a mixture thereof. The molecular mass of the surfactant is between 150 g/mol and 10,000 g/mol, advantageously between 250 g/mol and 1500 g/mol.
Dans le cas où le tensioactif est un tensioactif anionique, il est par exemple choisi parmi un alkylsulfate, un alkyle sulfonate, un alkylarylsulfonate, un alkylphosphate alcalin, un dialkylsulfosuccinate, un sel d'alcalino-terreux d'acides gras saturés ou non. Ces tensioactifs présentent avantageusement au moins une chaîne hydrocarbonée hydrophobe présentant un nombre de carbones supérieur à 5, voire 10 et au moins un groupement anionique hydrophile, tel qu'un sulfate, un sulfonate ou un carboxylate lié à une extrémité de la chaîne hydrophobe. Dans le cas où le tensioactif est un tensioactif cationique, il est par exemple choisi parmi un sel d'halogénure d'alkylpyridium ou d'alkylammonium comme le chlorure ou le bromure de n-éthyldodecylammonium, le chlorure ou le bromure de cétylammonium (CTAB). Ces tensioactifs présentent avantageusement au moins une chaîne hydrocarbonée hydrophobe présentant un nombre de carbones supérieur à 5, voire 10 et au moins un groupement cationique hydrophile, tel qu'un cation d'ammonium quaternaire. Dans le cas où le tensioactif est un tensioactif non ionique, il est par exemple choisi parmi des dérivés polyoxyéthylénés et/ou polyoxypropylénés des alcools gras, des acides gras, ou des alkylphénols, des arylphénols, ou parmi des alkyls glucosides, des polysorbates, des cocamides. In the case where the surfactant is an anionic surfactant, it is for example chosen from an alkyl sulfate, an alkyl sulfonate, an alkylarylsulfonate, an alkaline alkylphosphate, a dialkylsulfosuccinate, an alkaline earth salt of saturated or unsaturated fatty acids. These surfactants advantageously have at least one hydrophobic hydrocarbon chain having a number of carbons greater than 5, or even 10, and at least one hydrophilic anionic group, such as a sulfate, a sulfonate or a carboxylate linked to one end of the hydrophobic chain. In the case where the surfactant is a cationic surfactant, it is for example chosen from an alkylpyridium or alkylammonium halide salt such as n-ethyldodecylammonium chloride or bromide, cetylammonium chloride or bromide (CTAB) . These surfactants advantageously have at least one hydrophobic hydrocarbon chain having a number of carbons greater than 5, or even 10, and at least one hydrophilic cationic group, such as a quaternary ammonium cation. In the case where the surfactant is a non-ionic surfactant, it is for example chosen from polyoxyethylenated and/or polyoxypropylenated derivatives of fatty alcohols, fatty acids, or alkylphenols, arylphenols, or from alkyl glucosides, polysorbates, cocamides.
Dans un mode de réalisation, le tensioactif est le laurylsulfate de sodium (LSS) encore appelé dodécylsulfate de sodium et/ou le polyoxyethylène sorbitan monoleate (Polysorbate 80). In one embodiment, the surfactant is sodium lauryl sulfate (LSS) also called sodium dodecyl sulfate and/or polyoxyethylene sorbitan monoleate (Polysorbate 80).
De préférence, le tensioactif est le polyoxyethylène sorbitan monoleate (Polysorbate 80). Preferably, the surfactant is polyoxyethylene sorbitan monoleate (Polysorbate 80).
Dans un mode de réalisation, la teneur massique en tensioactif dans la coque est supérieure à 0,001% et est avantageusement supérieure à 0,1 %. Avantageusement, la concentration en masse de tensioactif est d'environ 0,03%. In one embodiment, the mass content of surfactant in the shell is greater than 0.001% and is advantageously greater than 0.1%. Advantageously, the mass concentration of surfactant is approximately 0.03%.
La coque peut également comprendre d’autres composés permettant notamment de renforcer sa résistance au séchage. Parmi ces composés on peut citer par exemple le biochar. De préférence le biochar est présent à raison de 0,1 à 20% en fraction volumique dans la coque, avantageusement de 0,5 à 15 % en fraction volumique dans la coque, de préférence de 1 à 10% en fraction volumique dans la coque. The shell may also include other compounds making it possible in particular to reinforce its resistance to drying. Among these compounds we can cite, for example, biochar. Preferably the biochar is present at a rate of 0.1 to 20% by volume fraction in the shell, advantageously from 0.5 to 15% by volume fraction in the shell, preferably from 1 to 10% by volume fraction in the shell .
Dans le cas d’une capsule à cœur huileux, la coque peut comprendre un agent de sédimentation, c’est-à-dire un agent inerte, de préférence minéral, permettant d’alourdir la capsule. En effet dans le cas de capsules à cœur huileux, celles-ci ont tendance à remonter à la surface quand elles sont comprises dans un liquide aqueux, ainsi l’ajout dans la coque d’un agent de sédimentation permet de les alourdir, de préférence afin que les capsules soient en suspension dans le liquide les contenant. Par exemple, un agent de sédimentation selon l’invention peut être choisi parmi le talc et/ou la silice. Dans ce cas, l’agent de sédimentation est présent à raison de 1 à 30% en fraction volumique dans la coque, avantageusement à raison de 5 à 20% en fraction volumique dans la coque. Cependant suivant la densité des capsules et du liquide les contenant, l’homme du métier est à même d’estimer la quantité d’agent de sédimentation nécessaire pour obtenir l’effet recherché. In the case of a capsule with an oily core, the shell may include a sedimentation agent, that is to say an inert agent, preferably mineral, making it possible to weigh down the capsule. Indeed, in the case of capsules with an oily core, they tend to rise to the surface when they are included in an aqueous liquid, so adding a sedimentation agent to the shell makes it possible to weigh them down, preferably so that the capsules are suspended in the liquid containing them. For example, a sedimentation agent according to the invention can be chosen from talc and/or silica. In this case, the sedimentation agent is present at a rate of 1 to 30% by volume fraction in the shell, advantageously at a rate of 5 to 20% by volume fraction in the shell. However, depending on the density of the capsules and the liquid containing them, those skilled in the art are able to estimate the quantity of sedimentation agent necessary to obtain the desired effect.
La coque des capsules a une épaisseur d’au moins 10 pm. En effet, les inventeurs ont montré qu’une telle épaisseur de coque conférait à la capsule une meilleure résistance au séchage. Si la membrane de la coque était fine, la capsule serait fragilisée et ne résisterait pas aux forces de cisaillement/stress mécaniques appliquées lors de la manipulation des capsules par l’opérateur par exemple ou aux conditions d’agitation des capsules lors de traitements physico-chimiques et risquerait fortement de se rompre. The shell of the capsules has a thickness of at least 10 μm. Indeed, the inventors have shown that such a shell thickness gives the capsule better resistance to drying. If the shell membrane were thin, the capsule would be weakened and would not resist the shear forces/mechanical stress applied during handling of the capsules by the operator for example or the conditions of shaking of the capsules during physico-chemical treatments and there is a strong risk of breaking.
Néanmoins, une membrane trop épaisse perdrait de son intérêt. However, a membrane that is too thick would lose its interest.
En particulier, la coque des capsules a donc une épaisseur comprise entre 10 pm et 1200 mm, avantageusement entre 20 pm et 800 pm, et plus particulièrement entre 20 pm et 400 pm. In particular, the shell of the capsules therefore has a thickness of between 10 pm and 1200 mm, advantageously between 20 pm and 800 pm, and more particularly between 20 pm and 400 pm.
En particulier, par rapport au diamètre de la capsule, la coque de la microcapsule a de préférence une épaisseur comprise entre 0,1% et 30 %, avantageusement entre 1 % et 20%, et plus particulièrement entre 10% et 20% du diamètre de la capsule. In particular, relative to the diameter of the capsule, the shell of the microcapsule preferably has a thickness of between 0.1% and 30%, advantageously between 1% and 20%, and more particularly between 10% and 20% of the diameter. of the capsule.
Procédé de séchage Drying process
L’invention porte sur un procédé de séchage de capsule dans lequel la capsule comprend une coque et un cœur, dans laquelle le cœur de la capsule est aqueux, ou de type émulsion huile dans eau, ou de type émulsion eau dans huile, dans laquelle la coque est une enveloppe gélifiée principalement composée d’au moins un biopolymère ; dans lequel ledit procédé de séchage comprend une étape de séchage sur lit fluidisé et/ou de lyophilisation. The invention relates to a capsule drying method in which the capsule comprises a shell and a core, in which the core of the capsule is aqueous, or of the oil-in-water emulsion type, or of the water-in-oil emulsion type, in which the shell is a gelled envelope mainly composed of at least one biopolymer; wherein said drying process comprises a fluidized bed drying and/or freeze-drying step.
Par « séchage sur lit fluidisé », on entend un procédé de mise en contact d’un gaz ascendant et d’un lit de particules (ici les capsules), où le poids des capsules est compensé par le courant due à l’écoulement du gaz. Le lit de capsules se comporte alors comme un fluide. Cette technique permet d’augmenter la surface gaz-capsules pour faciliter le séchage. Le séchage par lit fluidisé selon l’invention peut être sur lit fluidisé simple, lit fluidisé vibré, ou lit fluidisé à échangeur interne. By “drying on a fluidized bed”, we mean a process of bringing an ascending gas and a bed of particles (here the capsules) into contact, where the weight of the capsules is compensated by the current due to the flow of the gas. The bed of capsules then behaves like a fluid. This technique makes it possible to increase the gas-capsule surface area to facilitate drying. Drying by fluidized bed according to the invention can be on a simple fluidized bed, vibrated fluidized bed, or fluidized bed with internal exchanger.
De préférence, avant le séchage sur lit fluidisé les capsules selon l'invention sont enrobées par un agent anti-agglomérat. Preferably, before drying on a fluidized bed, the capsules according to the invention are coated with an anti-caking agent.
Par « agent anti-agglomérat » on entend un agent qui limite ou empêche l’agglutination des capsules ou la formation de mottes de capsules. Les agents antiagglomérats sont bien connus de l’homme du métier et comprennent notamment le carbonate de calcium, le phosphate tricalcique, le silicate de calcium, le silicate de magnésium, le stéarate de calcium, le stéarate de magnésium, le carbonate de magnésium, l’oxyde de magnésium, le dioxyde de silicium, le sodium aluminosilicate, le sodium ferrocyanide, le potassium ferrocyanide et leurs mélanges. By “anti-caking agent” we mean an agent which limits or prevents the clumping of capsules or the formation of capsule clumps. The anti-caking agents are well known to those skilled in the art and include in particular calcium carbonate, tricalcium phosphate, calcium silicate, magnesium silicate, calcium stearate, magnesium stearate, magnesium carbonate, magnesium oxide, silicon dioxide, sodium aluminosilicate, sodium ferrocyanide, potassium ferrocyanide and mixtures thereof.
De préférence, l’agent anti-agglomérat est le carbonate de calcium. Par « enrobage » on entend ici l’application d’une couche de poudre à la surface des capsules. Preferably, the anti-caking agent is calcium carbonate. By “coating” here we mean the application of a layer of powder to the surface of the capsules.
Par « lyophilisation », on entend la déshydratation par sublimation de l'eau. De préférence, les capsules sont immergées dans un bain de co-formulant, puis congelées à au moins -80°C puis lyophilisées. By “lyophilization” we mean dehydration by sublimation of water. Preferably, the capsules are immersed in a bath of co-formulant, then frozen at at least -80°C then freeze-dried.
Par « co-formulant » on entend un composé additionnel, sans activité biologique propre, servant à faciliter la manipulation des capsules ou à limiter la dégradation des capsules. By “co-formulant” we mean an additional compound, without its own biological activity, serving to facilitate the handling of the capsules or to limit the degradation of the capsules.
Par exemple un co-formulant peut-être un cryoprotectant. Les cryoprotectants pouvant être utilisés dans le cadre de l’invention sont le glycérol, la poly-L-lysine, le lactose, le tréhalose, l’inuline, le glutamate, l’ascorbate de sodium, le sulfate de magnésium, le bicarbonate de sodium, le saccharose, la maltodextrine, la poudre de lait et leurs mélanges. For example a co-formulant perhaps a cryoprotectant. The cryoprotectants which can be used in the context of the invention are glycerol, poly-L-lysine, lactose, trehalose, inulin, glutamate, sodium ascorbate, magnesium sulfate, bicarbonate of sodium, sucrose, maltodextrin, milk powder and mixtures thereof.
Dans un mode de réalisation préféré, les capsules sont immergées dans un bain de co-formulant comprenant du saccharose et plus préférentiellement comprenant une concentration comprise entre 50 et 500 g/L de saccharose. In a preferred embodiment, the capsules are immersed in a bath of co-formulant comprising sucrose and more preferably comprising a concentration of between 50 and 500 g/L of sucrose.
Dans un mode de réalisation préféré, les capsules sont immergées dans un bain de co-formulant comprenant de la maltodextrine et plus préférentiellement comprenant une concentration entre 50 et 500g/L de maltodextrine. In a preferred embodiment, the capsules are immersed in a bath of co-formulant comprising maltodextrin and more preferably comprising a concentration between 50 and 500g/L of maltodextrin.
Dans un mode de réalisation préféré, les capsules sont immergées dans un bain de co-formulant comprenant de la poudre de lait et plus préférentiellement comprenant une concentration entre 20 et 150 g/L. In a preferred embodiment, the capsules are immersed in a bath of co-formulant comprising milk powder and more preferably comprising a concentration between 20 and 150 g/L.
L’étape de congélation à -80°C est réalisée jusqu’à ce que le cœur des capsules soit à l’état solide. De préférence les capsules sont congelées à -80°C pendant au moins 6h, et plus préférentiellement pendant au moins 12 heures. The freezing step at -80°C is carried out until the core of the capsules is in a solid state. Preferably the capsules are frozen at -80°C for at least 6 hours, and more preferably for at least 12 hours.
Le procédé de séchage selon l’invention permet d’obtenir des capsules sous forme déshydratée. The drying process according to the invention makes it possible to obtain capsules in dehydrated form.
De préférence le procédé de séchage permet de diminuer d’au moins 70%, d’au moins 80% et plus particulièrement d’au moins 90% d’humidité en poids des capsules. Preferably the drying process makes it possible to reduce the humidity by weight of the capsules by at least 70%, at least 80% and more particularly by at least 90%.
De préférence la déshydratation est partielle, et les capsules obtenues ont un taux d’humidité inférieur à 10 %, mesuré par un analyseur d’humidité après déshydratation. Preferably the dehydration is partial, and the capsules obtained have a humidity level of less than 10%, measured by a humidity analyzer after dehydration.
L’invention concerne également une capsule déshydratée susceptible d’être obtenue par l’un quelconque des procédés de déshydratation de l’invention. The invention also relates to a dehydrated capsule capable of being obtained by any of the dehydration processes of the invention.
De préférence, les capsules obtenues ont un taux d’humidité inférieur à 10 % en poids, mesuré par un analyseur d’humidité après déshydratation. Sous forme déshydratée, le diamètre moyen de la capsule a tendance à diminuer. De préférence, la capsule selon l’invention a un diamètre moyen compris entre 10 pm et 4 mm sous forme déshydratée. Preferably, the capsules obtained have a humidity level of less than 10% by weight, measured by a humidity analyzer after dehydration. In dehydrated form, the average diameter of the capsule tends to decrease. Preferably, the capsule according to the invention has an average diameter of between 10 μm and 4 mm in dehydrated form.
Procédé de réhydratation Rehydration process
La présente invention concerne un procédé de réhydratation de capsules déshydratées, de préférence de capsules déshydratées selon l’invention, ledit procédé comprenant la mise en suspension des capsules déshydratées dans un milieu aqueux. The present invention relates to a process for rehydrating dehydrated capsules, preferably dehydrated capsules according to the invention, said process comprising suspending the dehydrated capsules in an aqueous medium.
De préférence le milieu aqueux est composé majoritairement d’eau, de préférence d’eau purifiée comme par exemple d’eau ultrapure. Le milieu aqueux peut être de l’eau physiologique c’est-à-dire de l'eau purifiée comprenant 0,9% (m/v) de chlorure de sodium. Preferably the aqueous medium is composed mainly of water, preferably purified water such as ultrapure water. The aqueous medium can be physiological water, that is to say purified water comprising 0.9% (m/v) sodium chloride.
En particulier, le milieu aqueux peut être de l’eau supplémentée en tensioactif par exemple avec du tween. In particular, the aqueous medium can be water supplemented with surfactant, for example with tween.
Ainsi dans un mode de réalisation de l’invention, si la capsule déshydratée ne comprend pas d’être vivant ou de microorganismes, le procédé de réhydratation comprend la mise en suspension des capsules déshydratées dans de l’eau ultrapure. Thus in one embodiment of the invention, if the dehydrated capsule does not include a living being or microorganisms, the rehydration process comprises suspending the dehydrated capsules in ultrapure water.
Dans un autre mode de réalisation de l’invention, si la capsule déshydratée comprend des bactéries et/ou des virus, le procédé de réhydratation comprend la mise en suspension des capsules déshydratées dans de l’eau physiologique. In another embodiment of the invention, if the dehydrated capsule comprises bacteria and/or viruses, the rehydration process comprises suspending the dehydrated capsules in physiological water.
Dans un autre mode de réalisation de l’invention, si la capsule déshydratée comprend des champignons ou des spores, le procédé de réhydratation comprend la mise en suspension des capsules déshydratées dans un milieu aqueux supplémentée en tensioactif, de préférence dans de l’eau physiologique supplémentée en Tween. In another embodiment of the invention, if the dehydrated capsule comprises fungi or spores, the rehydration process comprises suspending the dehydrated capsules in an aqueous medium supplemented with surfactant, preferably in physiological water supplemented with Tween.
De préférence les capsules déshydratées sont mises en suspension dans le milieu aqueux pendant au moins 30 minutes, de préférence de 30 minutes à 1 h. De préférence les capsules déshydratées sont mises en suspension à température ambiante, c’est-à-dire entre 10 et 25°C. De préférence la mise en suspension est favorisée par une agitation. Preferably the dehydrated capsules are suspended in the aqueous medium for at least 30 minutes, preferably from 30 minutes to 1 hour. Preferably the dehydrated capsules are suspended at room temperature, that is to say between 10 and 25°C. Preferably, suspension is promoted by agitation.
L’invention porte également sur une capsule réhydratée susceptible d’être obtenue par le procédé de réhydratation de l’invention. The invention also relates to a rehydrated capsule capable of being obtained by the rehydration process of the invention.
Dans la description et dans les exemples suivants, sauf indication contraire, les pourcentages sont des pourcentages en poids et les plages de valeurs libellées sous la forme « entre ... et ... », « allant de ... à ... », ou « supérieur à ... » incluent les bornes précisées. Dans toute la demande, le libellé "comprenant un" ou "comportant un" signifie "comprenant au moins un" ou "comportant au moins" un sauf si le contraire est spécifié. In the description and in the following examples, unless otherwise indicated, the percentages are percentages by weight and the ranges of values are denoted as "between ... and ...", "ranging from ... to ... ”, or “greater than…” include the specified limits. Throughout the application, the wording "comprising a" or "comprising a" means "comprising at least one" or "comprising at least" one unless otherwise specified.
Les exemples ci-après sont présentés à titre illustratif et non limitatif du domaine de l’invention. The examples below are presented by way of illustration and not limitation of the field of the invention.
Exemple 1 : test de lyophilisation de capsules et de leur réhydratation Example 1: freeze-drying test of capsules and their rehydration
Deux prototypes de capsules d’alginate sont testés dans lesquels le biochar inclus dans le cœur de la capsule sert de sonde afin d’estimer et/ou de quantifier le nombre de capsules dégradées et/ou la quantité de sonde perdue lors de la lyophilisation et de la réhydratation. Le premier prototype (prototype 1 ) comprend du biochar uniquement dans le cœur de la capsule. Le deuxième prototype comprend du biochar dans le cœur et dans la coque. Le biochar incorporé dans la coque des capsules a ici un rôle de rigidification de la coque.Two prototypes of alginate capsules are tested in which the biochar included in the core of the capsule serves as a probe in order to estimate and/or quantify the number of degraded capsules and/or the quantity of probe lost during lyophilization and rehydration. The first prototype (prototype 1) includes biochar only in the core of the capsule. The second prototype includes biochar in the core and shell. The biochar incorporated in the capsule shell has a role here in stiffening the shell.
Les prototypes de capsules d’alginate sont formés dans les conditions de production suivantes : Alginate capsule prototypes are formed under the following production conditions:
Le diamètre de la buse de l’injecteur est de 200 pm. Le débit total du fluide de cœur et de coque nommé Qtot est de 450 mL/h, le ratio de débits entre le fluide de cœur et de coque, nommé Rq est de 0,8 et confère à une épaisseur de membrane d’au moins 30 pm. The diameter of the injector nozzle is 200 pm. The total flow rate of the core and shell fluid named Qtot is 450 mL/h, the flow ratio between the core and shell fluid, named Rq is 0.8 and gives a membrane thickness of at least 30 p.m.
Les capsules sont produites par immersion dans un bain de chlorure de calcium. Un échantillon du bain de chlorure de calcium est prélevé pour le dosage du biochar présent dans ce bain. Il s’agit de la proportion de biochar qui n’a pas été encapsulé (le rendement d’encapsulation est légèrement inférieur à 100%). Les capsules sont ensuite collectées et lavées à l’eau pour éliminer le biochar qui serait déposé à la surface des capsules. The capsules are produced by immersion in a calcium chloride bath. A sample of the calcium chloride bath is taken for the determination of the biochar present in this bath. This is the proportion of biochar that has not been encapsulated (the encapsulation yield is slightly less than 100%). The capsules are then collected and washed with water to remove the biochar that would be deposited on the surface of the capsules.
Un échantillon de capsules humides est prélevé pour le dosage du biochar contenu dans la capsule. Pour cela, les capsules sont incubées dans une solution de PBS/EDTA permettant de solubiliser la coque d’alginate et ainsi de libérer le contenu. L’ajout de PBS permet de maintenir les conditions physiologiques de force ionique et de pH de la solution. Le reste des capsules est, par la suite, incubé dans un bain de co-formulant (SM-Sucrose c’est-à-dire un bain comprenant à 300 g/L de saccharose) et congelées à -80°C. A sample of wet capsules is taken for the determination of the biochar contained in the capsule. To do this, the capsules are incubated in a PBS/EDTA solution to solubilize the alginate shell and thus release the contents. The addition of PBS makes it possible to maintain the physiological conditions of ionic strength and pH of the solution. The rest of the capsules are subsequently incubated in a co-formulant bath (SM-Sucrose, i.e. a bath comprising 300 g/L of sucrose) and frozen at -80°C.
Ensuite ces capsules sont lyophilisées. Après lyophilisation, les capsules sont lavées par mise en suspension dans une solution d’eau ultrapure afin de permettre le relargage dans la phase continue puis de doser le biochar issu de la rupture des capsules lors de l’étape de congélation/lyophilisation. Après l’étape de lavage, un échantillon est prélevé pour le dosage du biochar contenu dans les capsules. Then these capsules are freeze-dried. After freeze-drying, the capsules are washed by suspending them in an ultrapure water solution in order to allow release in the continuous phase and then to measure the biochar resulting from the rupture of the capsules during the step. freezing/lyophilization. After the washing step, a sample is taken for the determination of the biochar contained in the capsules.
Les colonnes nommées « capsules hydratées » et « capsules déshydratées » comprennent la mesure de la DO (densité optique) et l’estimation de la quantité de biochar retrouvée après dissolution des capsules. Cette dissolution est réalisée par solubilisation de l’hydrogel d’alginate qui compose la coque des capsules. Pour cela, une solution de PBS/EDTA (tampon phosphate salin/ Acide Ethylène Diamine Tétra-acétique) est utilisée et permet de libérer le contenu des capsules dans la phase continue. L’EDTA permet en effet de chélater les ions calcium présents dans la coque. The columns named “hydrated capsules” and “dehydrated capsules” include the measurement of the OD (optical density) and the estimation of the quantity of biochar found after dissolution of the capsules. This dissolution is achieved by solubilizing the alginate hydrogel which makes up the shell of the capsules. For this, a solution of PBS/EDTA (phosphate buffer saline/Ethylene Diamine Tetraacetic Acid) is used and allows the contents of the capsules to be released in the continuous phase. EDTA makes it possible to chelate the calcium ions present in the shell.
Les colonnes nommées « bain de calcium » et « tampon de lavage » comprennent la quantité de sonde perdue dans ces bains ou ces tampons. The columns labeled “Calcium Bath” and “Wash Buffer” include the amount of probe lost in these baths or buffers.
[Table 1] Tableau 1 : quantification du biochar à chaque étape du traitement du prototype 1
Figure imgf000011_0001
[Table 1] Table 1: quantification of biochar at each stage of the treatment of prototype 1
Figure imgf000011_0001
Ainsi en proportions, la fraction [tampon de lavage des capsules déshydratées] représente 7 % de quantité totale de biochar et la fraction [capsules déshydratées] représente 100- 7,06 = 92,94%. Thus in proportions, the fraction [dehydrated capsule washing buffer] represents 7% of the total quantity of biochar and the fraction [dehydrated capsules] represents 100-7.06 = 92.94%.
La perte de biochar lors du procédé de lyophilisation est donc estimée à 7% seulement avec le prototype 1 . [Table 2] Tableau 2 : quantification du biochar à chaque étape du traitement du prototype 2
Figure imgf000012_0001
The loss of biochar during the freeze-drying process is therefore estimated at only 7% with prototype 1. [Table 2] Table 2: quantification of biochar at each stage of the treatment of prototype 2
Figure imgf000012_0001
La perte de biochar lors du procédé de lyophilisation est donc estimée à 0,5% seulement avec le prototype 2. La perte de biochar est donc réduite en présence de biochar dans la coque des capsules d’un facteur de 10, passant de de 7% à 0,5% The loss of biochar during the freeze-drying process is therefore estimated at only 0.5% with prototype 2. The loss of biochar is therefore reduced in the presence of biochar in the shell of the capsules by a factor of 10, from 7 % to 0.5%
Exemple 2 : test de lyophilisation de capsules comprenant un bactériophage et de leur réhydratation Example 2: freeze-drying test of capsules comprising a bacteriophage and their rehydration
Deux prototypes de capsules d’alginate sont testés dans lesquels des bactériophages sont inclus dans le cœur de la capsule et servent de sonde vivante afin de quantifier le nombre de capsules dégradées et/ou la quantité de sonde perdue lors de la lyophilisation et de la réhydratation. Two prototype alginate capsules are tested in which bacteriophages are included in the core of the capsule and serve as a living probe in order to quantify the number of degraded capsules and/or the amount of probe lost during lyophilization and rehydration .
Le premier prototype (prototype 1) ne comprend pas de biochar. Le deuxième prototype (prototype 2) comprend du biochar dans la coque. The first prototype (prototype 1) does not include biochar. The second prototype (prototype 2) includes biochar in the hull.
Les prototypes de capsules d’alginate sont formés dans les conditions de production suivantes : Alginate capsule prototypes are formed under the following production conditions:
Le débit total du fluide de cœur et de coque nommé Qtot est de 500 mL/h, le ratio de débits entre le fluide de cœur et de coque, nommé Rq est de 0,8. The total flow rate of the core and shell fluid, named Qtot, is 500 mL/h, the flow ratio between the core and shell fluid, named Rq, is 0.8.
Le diamètre moyen des deux prototypes de capsules est respectivement de 462 pm avec un coefficient de variation de 17% et de 542 pm avec un coefficient de variation de 18%. L’épaisseur de la coque de ces prototypes est au moins de 30 pm. The average diameter of the two capsule prototypes is respectively 462 pm with a coefficient of variation of 17% and 542 pm with a coefficient of variation of 18%. The thickness of the shell of these prototypes is at least 30 pm.
Les bactériophages de la souche M13K07 sont des bactériophages lytiques qui agissent sélectivement et spécifiquement contre le pathogène bactérien Escherichia coli. [Table 3] Tableau 3 : Quantification des bactériophages lors de la formation des capsules et de leur séchage
Figure imgf000013_0002
Bacteriophages of strain M13K07 are lytic bacteriophages that act selectively and specifically against the bacterial pathogen Escherichia coli. [Table 3] Table 3: Quantification of bacteriophages during capsule formation and drying
Figure imgf000013_0002
[Table 4] Tableau 4 : Evaluation des pertes de bactériophages lors du séchage des capsules
Figure imgf000013_0003
[Table 4] Table 4: Evaluation of bacteriophage losses during capsule drying
Figure imgf000013_0003
Les calculs sont effectués ainsi :
Figure imgf000013_0001
The calculations are carried out as follows:
Figure imgf000013_0001
Le « rendement d’encapsulation par la méthode dite bain de calcium » est calculé en mesurant la quantité de bactériophage restée dans le bain est donc non encapsulée, par rapport à la quantité de bactériophage utilisé lors de la formation des capsules. The “encapsulation yield by the so-called calcium bath method” is calculated by measuring the quantity of bacteriophage remaining in the bath and therefore not encapsulated, in relation to the quantity of bacteriophage used during the formation of the capsules.
[Table 5] Tableau 5 : Rendements de l’encapsulation des bactériophages
Figure imgf000013_0004
Figure imgf000014_0001
[Table 5] Table 5: Yields of bacteriophage encapsulation
Figure imgf000013_0004
Figure imgf000014_0001
La perte en survie des bactériophages au cours de la lyophilisation est estimée à 5%. The loss of bacteriophage survival during freeze-drying is estimated at 5%.
Exemple 3 : Test de séchage sur lit fluidisé des capsules Example 3: Drying test on fluidized bed of capsules
Le séchage sur lit d’air fluidisé d’un prototype de capsules d’alginate contenant une souche bactérienne a été testé. Le prototype de capsules d’alginate est formé dans les conditions de production suivantes : Drying on a fluidized air bed of a prototype of alginate capsules containing a bacterial strain was tested. The prototype alginate capsules are formed under the following production conditions:
Le diamètre de la buse de l’injecteur est de 150 pm. Le débit total du fluide de cœur et de coque nommé Qtot est de 350 mL/h, le ratio de débits entre le fluide de cœur et de coque, nommé Rq est de 1 , conférant aux capsules une épaisseur de membrane d’au moins 20 pm. The diameter of the injector nozzle is 150 pm. The total flow rate of the core and shell fluid named Qtot is 350 mL/h, the flow ratio between the core and shell fluid, named Rq is 1, giving the capsules a membrane thickness of at least 20 p.m.
Une fois produites et lavées à l’eau physiologique, les capsules sont mélangées à du carbonate de calcium en proportions massiques 1 :1 avant de les sécher au lit d’air fluidisé pendant 30 minutes. La température atteinte au sein de l’enceinte reste inférieure à 45°C.Once produced and washed with physiological water, the capsules are mixed with calcium carbonate in 1:1 mass proportions before drying them in a fluidized air bed for 30 minutes. The temperature reached within the enclosure remains below 45°C.
Une fois sèches, les capsules sont lavées par remise en suspension dans de l’eau physiologique pour éliminer le carbonate de calcium. Un échantillon de capsules est prélevé pour déterminer la concentration bactérienne contenue dans les capsules. Once dry, the capsules are washed by resuspension in physiological water to remove the calcium carbonate. A sample of capsules is taken to determine the bacterial concentration contained in the capsules.
Les concentrations bactériennes dans les produits humides et secs sont respectivement de 5,48.108 UFC/g et 4,11.105 UFC/g. Les inventeurs ont observé que la concentration bactérienne du prototype après séchage au lit d’air fluidisé reste relativement élevé. The bacterial concentrations in the wet and dry products are 5.48.10 8 CFU/g and 4.11.10 5 CFU/g, respectively. The inventors observed that the bacterial concentration of the prototype after drying in a fluidized air bed remained relatively high.

Claims

REVENDICATIONS
1. Procédé de séchage de capsule dans lequel la capsule comprend un cœur et une coque, dans laquelle le cœur de la capsule est aqueux, ou de type émulsion huile dans eau, ou de type émulsion eau dans huile, dans laquelle la coque est une enveloppe gélifiée principalement composée d’au moins un biopolymère ; dans lequel la coque a une épaisseur d’au moins 10 pm ; dans lequel ledit procédé de séchage comprend une étape de séchage sur lit fluidisé et/ou de lyophilisation. 1. Capsule drying process in which the capsule comprises a core and a shell, in which the core of the capsule is aqueous, or of the oil-in-water emulsion type, or of the water-in-oil emulsion type, in which the shell is a gelled envelope mainly composed of at least one biopolymer; in which the shell has a thickness of at least 10 μm; wherein said drying process comprises a fluidized bed drying and/or freeze-drying step.
2. Procédé de séchage de capsule selon la revendication 1 , dans lequel la coque est principalement composée d’alginate. 2. Capsule drying process according to claim 1, in which the shell is mainly composed of alginate.
3. Procédé de séchage selon l’une quelconque des revendications 1 à 2 dans lequel la capsule avant le séchage a un ratio volumique cœur/coque est compris entre 0,5 et 2. 3. Drying method according to any one of claims 1 to 2 in which the capsule before drying has a core/shell volume ratio of between 0.5 and 2.
4. Procédé de séchage selon l’une quelconque des revendications 1 à 3 dans lequel les capsules sont immergées dans un bain de co-formulant, puis congelées à au moins -80°C puis lyophilisées. 4. Drying process according to any one of claims 1 to 3 in which the capsules are immersed in a bath of co-formulant, then frozen at at least -80°C then freeze-dried.
5. Procédé de séchage selon l’une quelconque des revendications 1 à 3 dans lequel avant le séchage sur lit fluidisé les capsules selon l'invention sont enrobées par un agent anti-agglomérat. 5. Drying method according to any one of claims 1 to 3 in which before drying on a fluidized bed the capsules according to the invention are coated with an anti-caking agent.
6. Capsule déshydratée susceptible d’être obtenue par l’un quelconque des procédés suivant les revendications 1 à 5. 6. Dehydrated capsule capable of being obtained by any of the processes according to claims 1 to 5.
7. Procédé de réhydratation de capsule déshydratée selon la revendication 6, comprenant la mise en suspension des capsules déshydratées dans un milieu aqueux. 7. Process for rehydrating a dehydrated capsule according to claim 6, comprising suspending the dehydrated capsules in an aqueous medium.
8. Capsule réhydratée susceptible d’être obtenue par le procédé de réhydratation de capsules selon la revendication 7. 8. Rehydrated capsule capable of being obtained by the capsule rehydration process according to claim 7.
PCT/EP2023/067859 2022-06-30 2023-06-29 Capsule drying method WO2024003268A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2939012A1 (en) 2008-12-01 2010-06-04 Capsum PROCESS FOR MANUFACTURING A SERIES OF CAPSULES, AND ASSOCIATED SERIES OF CAPSULES
WO2017205586A1 (en) * 2016-05-27 2017-11-30 Corning Incorporated Biodegradable microbeads
CN109734174A (en) * 2019-02-12 2019-05-10 陕西科技大学 A kind of pair of load core shell hydrogel glue and its preparation method and application
CN110339393A (en) * 2019-07-19 2019-10-18 吉林大学 It is a kind of based on hydrogel-core-shell particles wound dressing and preparation method thereof
EP3967157A1 (en) * 2020-09-09 2022-03-16 Xampla Limited Plant-based microcapsules

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FR2939012A1 (en) 2008-12-01 2010-06-04 Capsum PROCESS FOR MANUFACTURING A SERIES OF CAPSULES, AND ASSOCIATED SERIES OF CAPSULES
WO2017205586A1 (en) * 2016-05-27 2017-11-30 Corning Incorporated Biodegradable microbeads
CN109734174A (en) * 2019-02-12 2019-05-10 陕西科技大学 A kind of pair of load core shell hydrogel glue and its preparation method and application
CN110339393A (en) * 2019-07-19 2019-10-18 吉林大学 It is a kind of based on hydrogel-core-shell particles wound dressing and preparation method thereof
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