Title of Invention	GELLAN SEAMLESS BREAKABLE CAPSULE AND PROCESS FOR MANUFACTURING THEREOF
Abstract	The invention relates to a process for manufacturing a seamless breakable capsule, comprising - co-extruding an external and hydrophilic liquid phase, and an internal and lipophilic liquid phase, in order to form a capsule constituted of a core comprising then internal and lipophilic phase, and a shell comprising the external and hydrophilic phase, - immersing into an aqueous solution containing a curing agent, wherein the external liquid phase includes a gelling agent comprising gellan gum alone or in combination with another gelling agent, a filler, and a divalent metal sequestering agent, and to breakable capsules comprising a core and a shell, wherein the shell includes a gelling agent comprising gellan gum alone or in combination with another gelling agent, a filler, and a divalent metal sequestering agent.

Title of Invention

GELLAN SEAMLESS BREAKABLE CAPSULE AND PROCESS FOR MANUFACTURING THEREOF

Abstract

The invention relates to a process for manufacturing a seamless breakable capsule, comprising - co-extruding an external and hydrophilic liquid phase, and an internal and lipophilic liquid phase, in order to form a capsule constituted of a core comprising then internal and lipophilic phase, and a shell comprising the external and hydrophilic phase, - immersing into an aqueous solution containing a curing agent, wherein the external liquid phase includes a gelling agent comprising gellan gum alone or in combination with another gelling agent, a filler, and a divalent metal sequestering agent, and to breakable capsules comprising a core and a shell, wherein the shell includes a gelling agent comprising gellan gum alone or in combination with another gelling agent, a filler, and a divalent metal sequestering agent.

Full Text	WO 2007/012981 PCT/IB2006/002905 1 GELLAN SEAMLESS BREAKABLE CAPSULE AND PROCESS FOR MANUFACTURING THEREOF. The present invention relates to a breakable capsule having a fluid core and a solid or fluid breakable shell. In this invention, the term "capsule" means a spherical or substantially spherical delivery system of a substance, said substance being hereinafter referred to as "the core", and said substance being encapsulated into a shell, the shell being breakable and releasing the core when broken or ruptured. The term fluid means flowing as opposed to being in a solid state. According to the invention, the term fluid includes finely divided solids, such as a powder, and also gel, or any physical state of a product wherein said product changes shape or direction uniformly, in response to an external force imposed upon it. According to the invention, fluid preferably refers to a flowable or gellified product. The term "breakable capsule" refers to a capsule as hereabove defined, wherein the shell can be ruptured by means of a pressure, which results in the release of the core. According to an embodiment, the capsule of the invention may be specifically designed to be incorporated into a fluid medium such as for example a gel, a pasty or a liquid medium containing water; in this embodiment, the capsules may be suspended or mixed by any suitable means in order to bring an visual effect of homogeneous dispersion of the capsules in the medium; advantageously, the shell and/or the core of the capsule is coloured. According to another embodiment, the capsule of the invention is WO 2007/012981 PCT/IB2006/002905 2 dispersed into a solid or fluid medium, such as for example a powder; advantageously, the shell and/or the core of the capsule is coloured. Such capsules are useful for numerous applications, such as in oral care application (toothpaste, mouthwash, gums...) , in food applications such as confectionary, dairy, bakery, savory, in neutraceutical applications or in pharmaceutical or in personal care products such as cosmetic products and the like. In the present patent application, the term "capsule" will be used to designate any size of capsules, including macrocapsules and microcapsules and preferably capsule which larger diameter is from 0.5 mm up to 8 mm, preferably 1 to 5 mm; more preferably 1.2 to 3 mm. It is of particular interest to obtain seamless capsules, as the breakability of a welded capsule (also designated in the prior art as softgel or hard capsule) may be influenced by the easy or unwanted rupture of the weld. Fuji patent application JP10291928 describes a capsule obtained through a co-extrusion process, wherein the external liquid phase comprises gellan and calcium salts. Gellan gum, first discovered in 1978, is produced by the microorganism Sphingomonas elodea. The Applicant has found that the production of gellan capsule through the Fuj i process was not satisfactory and resulted in poor quality capsules and in processing difficulties, because the gellan was actually gelling during the co-extrusion, and it was not possible to obtain spherical and homogeneous breakable capsules. WO 2007/012981 PCT/IB2006/002905 3 For this reason, the Applicant tried to improve the Fuji process and found that the drawbacks of the prior art process may be due to the presence of calcium salts, and more generally to divalent metal salts in gellan during the co-extrusion step. Thus, the Applicant carried out a process wherein the co-extrusion liquid phase containing gellan was performed in absence of calcium salts, and observed that, surprisingly, the resulting capsules had the required spherical or substantially spherical shape and homogeneous sizes. However, the capsules thus obtained could not be used as such, because the shell was too soft and the resulting capsules were not breakable capsules; the Applicant found a solution to this subsequent technical problem by contacting the capsules with divalent metal ions, preferably calcium or magnesium ions, or by using organic acid solution, once the co-extrusion process is finished, and this finally lead to satisfactory breakable capsules. Thus, this invention relates to a process for manufacturing seamless breakable capsules and to new seamless breakable capsules. The process of the invention comprises a step (A) of co-extrusion of an external and hydrophilic liquid phase and an internal and lipophilic liquid phase, in order to form a capsule having a core comprising the internal and lipophilic phase and a shell comprising the external and hydrophilic phase; and a step (B) of washing and immersing the capsules into an aqueous solution preferably containing a curing agent, the curing agent being one of the means for making the shell breakable as required for the intended use; optionally a step (C) of drying the obtained capsules WO 2007/012981 PGT/IB2006/002905 4 or optionally a step (D) of suspending the capsules into an fluid medium. The co-extrusion process comprises three main stages: compound drop formation, shell solidification and capsule collection. The compound drop is a sphere of the liquid fill phase inside the shell phase. The liquid fill phase is hereinafter referred to as "the core". The shell phase is hereinafter referred to as "the shell". According to the invention, the external liquid phase includes a gelling agent comprising gellan gum, alone or in combination with at least one suitable gelling agent, a filler, and a metal sequestering agent, the liquid preferably being aqueous, more preferably the liquid is water, preferably desionized or osmozed water. By "gelling agent" in the meaning of this invention, it is referred to an agent able to convert an aqueous phase from a flowable or fluid liquid to a solid or a gel. By "sequestering agent" in the meaning of this invention it is referred to any agent complexing, chelating or sequestering bivalent ions such as calcium or magnesium ions. The term "substantially", when referring to a number or value, means + or - 10 % of the value; when referring to a sphere, it means a distorted sphere which larger diameter is + or - 10 % of the diameter of the expected sphere. The term "wet capsule" in the meaning of this invention, refers to a capsule which shell includes a positive amount of water. The term wet capsule is used for the calculation of percentages of ingredients in the final WO 2007/012981 PCT/IB2006/002905 5 product or shell, as opposed to the calculation based on the dry weight of said final product or shell. The breakable capsule according to the invention preferably has a crush strength from 0.01 to 5 kp, preferably from 0.1 to 2.5 kp, edge values being included. The crush strength of the capsule is measured by continuously applying a load vertically onto one particle until rupture. The crush strength of the capsules in the present invention is measured by using a texturometer TA.XT plus from Micro Stable System in compression mode or a LLOYD - CHATILLON Digital Force Gauge, Model DFIS 50, having a capacity of 25Kg, a resolution of 0.02 Kg, and an accuracy of +/- 0,15 %. The force gauge is attached to a stand; the capsule is positioned in the middle of a plate that is moved up with a manual thread screw device. Pressure is then applied manually and the gauge records the maximum force applied at the very moment of the rupture of the capsule, (measured in Kg or in Lb) . Rupture of the capsule results in the release of the core. Gellan gum is a hydrocolloid which, according to the invention, can be used as the sole gelling agent of the external liquid phase, or in combination with at least one ohter gelling agent. Other suitable gelling agents may be alginates, agar, carragheenan, pectines, xanthan gum, Arabic gum, tara gum, ghatti gum, karaya gum, dextran, curdlan, welan gum, rhamsan gum or modified starches. Suitable gellan gums are for example, but not limited to deacylated gellan gum. Kelcogel® can be mentioned as a suitable gellan gum. The amount of gelling agent present in the shell is 4 to 95%, preferably 5 to 75%, even more preferably is WO 2007/012981 PCT/IB2006/002905 6 10 to 50%, more preferably 12 to 40 % by weight of the total dry weight of the shell. When used in combination with at least another gelling agent, the weight ratio between gellan gum and the other gelling agent(s) is from 80/20 to 20/80, preferably 75/25 to 25/75, and even more preferably from 60/40 to 50/50. Preferably, the weight ratio of gelling agent / dried shell is greater than 10%, preferably greater than 12, more preferably greater than 15%. The filler is any suitable material that can increase the percentage of dry material in the external liquid phase or bring filming properties. Increasing the dry material amount in a shell results in solidifying the shell, and in making it physically more resistant or impermeable. Preferably, the filler is selected from the group comprising starch derivatives such as dextrin, maltodextrin, polyol, cyclodextrin (alpha, beta or gamma), or cellulose derivatives such as hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), methylcellulose (MC), carboxymethylcellulose (CMC), polyethylene glycol derivatives, polyvinyl alcohol, polyols or mixture thereof. The amount of filler in the shell is at most 98.5%, preferably from 25 to 95% and even more preferably from 50 to 80% by weight on the total dry weight of the shell. Using a divalent metal sequestering or complexing agent allows trapping the divalent metal ions which are possibly present in the components of the liquid phase including water and which have a gelling effect on gellan. Thus, the use of a divalent metal sequestering agent, WO 2007/012981 PCT/IB2006/002905 7 preferably of a calcium ion sequestering agent, allows the gellan to be co-extruded without undesirable or uncontrollable gelling during the co-extrusion. The amount of sequestering agent is at most 2%, preferably at most 1% and even more preferably at most 0.5% by weight of the total dry weight of the shell. Preferably, the water used for the external phase is deionized water and/or osmozed water; using processing water remains possible but needs adjusting the amount of divalent metal sequestering agent. The sequestering agent is a metal salt, preferably selected from the group comprising trisodium citrate, trisodium phosphate, tetrasodium pyrophosphate, sodium hexametaphosphate and mixtures thereof. The hydrophilic external liquid phase may further comprise at least one plasticizer, which may be at least one of glycerol, sorbitol, maltitol, triacetine or polyethylene glycol type product, or a polyalcohol with plasticizing or humectant properties. Advantageously, the hydrophilic external liquid phase further comprises at least one colouring agent or pigment; according to a first embodiment, the colouring agent or the pigment is in a form of a powder or a suspension stable in an aqueous medium. According to another embodiment of the invention, the liquid phase may include perfumes, aromas, fragrances or any odoring agent. According to one embodiment of the invention, the co-extrusion step (A) of the process can be performed at a temperature being from room temperature to 100°C. Advantageously, it is performed at room temperature, which means between 18 and 30°C, preferably 20-25 °C under atmospheric pressure. WO 2007/012981 PCT/IB2006/002905 8 The co-extrusion step is a synchronous extrusion of two liquids: the external and hydrophilic liquid phase, and the internal and lipophilic liquid phase which can be performed using an apparatus and a process as described in EP 513603, the disclosure of which is herein incorporated by reference. According to an embodiment of the invention, after the co-extrusion step (A), the solidification step is performed by keeping cold the capsules in order to ensure correct gelling of the shell, for example by contacting them with a cold bath. The cold bath may preferably be cold oil or cold emulsion. Cold means any temperature below 18"°C, preferably the temperature is from 2 to 10 °C, more preferably 4 to 6 °C. According to an embodiment of the invention, the capsules may then be centrifuged in order to remove the surplus oil, and/or washed with organic solvent (such as acetone, ethyl acetate, ethanol, petroleum ether, etc.) also to remove the surplus oil, and optionally dried in a air flow at controlled temperature and humidity. The relative humidity of the drying air is 20% to 60%, preferably 3 0 to 50%; the temperature of the drying air is of 15 to 60 °C, preferably 35 to 45 °C. According to another embodiment, the capsules are preferably immersed into an aqueous solution or an emulsion containing a curing agent which comprises a divalent salt and optionally an acid. The effect of the immersion step is to wash out the oil remaining at the periphery of the capsule, and to gradually strengthen the shell, notably through dehydration and osmotic equilibrium. According to one embodiment of the invention, after immersion, the capsules are dried in the same WO 2007/012981 PCT/IB2006/002905 9 conditions as mentioned above. According to another embodiment of the invention, after immersion, the capsules are not dried. The curing agent preferably comprises divalent metal ions, or a mixture of divalent metal ions, such as calcium ions or magnesium ions. The aqueous solution or emulsion containing the curing agent is preferably a divalent metal salt solution, preferably containing calcium or magnesium salts, more preferably, calcium dichloride, calcium carbonate, calcium sulfate or dicalcium phosphate. This solution may be the aqueous phase of an oil-in-water emulsion. This solution can be at a temperature comprised between 2°C and room temperature. Advantageously, the aqueous solution containing the curing agent is maintained under acid conditions of pH, and preferably at a pH less than 5, more preferably from 2 to 4. According to a preferred embodiment of the invention, the aqueous solution or emulsion containing a curing agent is a calcium chloride solution having a pH of 3 to 4. The aqueous solution containing the curing agent can also contain preservatives or bactericides such as benzoate, parabens, diols, cetylpyridinium chloride, diazolidinyl urea or any preservatives used for food, pharmaceutical or cosmetic products. According to one embodiment of the invention, the process comprises the steps of co-extruding the above mentioned external and internal liquid phases, optionally solidifying and/or gelling the surface of the shell by keeping the capsule under cold conditions, as explained herein above, optionally centrifugating, optionally washing WO 2007/012981 PCT/IB2006/002905 10 the so-obtained capsules with an organic solvent, immersing the resulting capsules into an aqueous solution containing a curing agent, and optionally drying the capsules. According to one embodiment of the invention, the solidifying/gelling/curing steps can be gathered into a single step, for example by dipping the capsules into a bath, under cold conditions, containing the divalent metal salts, preferably calcium or magnesium salts, more preferably, calcium dichloride, calcium sulfate or dicalcium phosphate. This bath may be an oil-in-water emulsion. The capsules manufactured through the process according to the invention are substantially or perfectly spherical and very homogeneous in size. This invention also relates to breakable capsules which are preferably seamless capsules susceptible to be obtained through the process according to the invention. The capsule of the invention comprises a core and a shell, and said shell includes a gelling agent comprising gellan gum alone or in combination with another gelling agent, a filler, and a divalent metal sequestering agent. Preferably the gelling agent of the shell is a combination of gellan and of at least one other gelling agent selected from the group consisting of gelatin and hydrocolloids such as agar, carragheenan, pectins, xanthan gum, alginate, tara gum, arabic gum, ghatti gum, caroub gum, cellulose gum, dextran, curdlan, welan gum, rhamsan gum or modified starches. According to a preferred embodiment of the invention the filler and the sequestering agent, are as described hereinabove. WO 2007/012981 PCT/IB2006/002905 11 According to another embodiment, the shell further comprises a plasticizer as described hereinabove. The amount of plasticizer ranges from 0.1% to 30% by weight, preferably from 2% to 15% by weight, and even more preferably from 3 to 10% by weight of the total dry weight of the shell. According to the intended use of said capsules, the shell may contain other additives such as perfumes, aromas, or any flavoring agent. According to the intended use of said capsule, the shell may comprise coloring agent such as pigments, titanium dioxide, iron oxides, carbon black, or any type of food, oral care, cosmetic or pharmaceutical pigment such as Covasorb colors distributed by LCW. The shell of a breakable capsule according to the invention represents by weight 8 to 50% of the total weight of said capsule, preferably 10 to 40%, more preferably 20 to 3 0%. The amount of water present in the shell is of 1 to 60 %, preferably 5 to 40 % the capsule remaining breakable even at the higher percentages. According to a preferred embodiment, the breakable capsule according to the invention has a crush strength of from 0.01 to 5, preferably from 0.01 to 2.5 kp. Advantageously, the shell thickness of the capsule is 10-500 microns, preferably 30-150 microns, more preferably 50-60 microns. The ratio diameter of the WO 2007/012981 PCT/IB2006/002905 12 capsule/thickness of the shell is in the range of 1 to 100, preferably 5 to 30. The core of the capsule is preferentially composed of a mixture of materials or products which are lipophilic or partially soluble in ethanol, or of molecules formulated as oil/water/oil emulsions. The core of a breakable capsule according to the invention represents by weight 50 to 92% of the total weight of said capsule, preferably 60 to 90%, more preferably 70 to 80%. The core of the capsule may be composed of one or more lipophilic solvents conventionally used in the food, pharmaceutical or cosmetic industries. In a preferred embodiment, these lipophilic solvents may be triglycerides, especially medium chain triglycerides, and in particular triglycerides of caprylic and capric acid, or mixtures of triglycerides such as vegetable oil, hydrogenated oil, coconut oil, palm oil, olive oil, sunflower oil, corn oil, linseed oil, cottonseed oil, groundnut oil, grape seed oil, wheat germ oil, fish oil, beet fat, mineral oils and silicone oils. The amount of lipophilic solvent in the core of a capsule according to the invention is of the order of 0.01 to 90%, preferentially 25 to 75%, of the total weight of the capsule. The core may also comprise one or more aromatic or fragrance molecules as conventionally used in the formulation of flavoring or fragrance compositions. Mention will in particular be made of aromatic, terpenic and/or sesquiterpenic hydrocarbons, and more particularly essential oils, alcohols, aldehydes, phenols, carboxylic acids in their various forms, aromatic acetals and ethers, WO 2007/012981 PCT/IB2006/002905 13 nitrogenous heterocycles, ketones, sulfides, disulfides and mercaptans which may be aromatic or non aromatic. It may also comprise one or more molecules or extracts for cosmetic use. The core may also comprise one or more fillers as used in aromatic emulsions. Mention will be made of dammar gum, wood resins of the ester gum type, sucrose acetate isobutyrate (SAIB) or brominated vegetable oils. The function of these weighting agents is to adjust the density of the liquid core. The core may also comprise one or more sweeteners, which may be provided in the form of a solution or suspension in ethanol. Examples of suitable sweeteners may be, but is not limited to, aspartame, saccharine, NHDC, sucralose, acesulfame, neotame, thaumatin, steviosides, etc. The core may also comprise one or more "sensate" aromatic agents, which provide either a freshening effect or a hot effect in the mouth. Suitable freshening agents may be, but are not limited to, menthyl succinate and derivatives thereof, in particular Physcool® marketed by the Applicant. A suitable hot effect agent may be, but is not limited to, vanillyl ethyl ether. The flavoring agents that can be solubilized in the solvent of the core of the capsule include, but are not limited to, natural or synthetic aromas and/or fragrances. Examples of suitable fragrances are fruity, confectionery, floral, sweet, woody fragrances. Examples of suitable aromas are vanilla, coffee, chocolate, cinnamon, mint. The core may also comprise a lipophilic color such as fake colors but also natural colors such as paprika oleoresin, WO 2007/012981 PCT/IB2006/002905 14 turmeric oleoresin, carotenes, chlorophyllin, or any other suitable natural coloring product. The core may also include lipophilic active agents, such as vitamins, more preferably vitamine B; fatty acids, preferably omega 3 and natural extracts of plants. The capsules according to the invention can be included in various products, such as food products, oral care products, nutraceutical products, pharmaceutical products, cleaning products and cosmetic products. The invention thus relates to a food product including breakable capsules according to the invention; an oral care product including breakable capsules according to the invention, preferably a toothpaste including breakable capsules according to the invention; a pharmaceutical product including breakable capsules according to the invention; a fragrance including breakable capsules according to the invention. The capsules of the invention may be within a slurry, in suspension in a gel, preferably carried out with a gel forming agent such as xanthan gum, gellan gum, CMC or Carbopol, araboxymethyl cellulose, or any polymer commonly used as suspending agent and optionally comprising preservatives and stabilizers. The total weight of the capsule of the invention depends on its diameter and on the amount of core filling the shell. According to an embodiment of the invention, the total weight of the capsule is within the range of 0.1 to 50 mg, preferably 0.2 to 20 mg, more preferably 0.5 to 10 mg. WO 2007/012981 PCT/IB2006/002905 15 The invention is hereunder illustrated by the following examples, which should not be considered as limiting the scope of the invention. EXAMPLES Example 1 Menthol Capsules (referred as 3039/A1) are prepared by co- extruding an outer liquid phase and an internal liquid phase presenting the following compositions: Outer liquid phase Dry matter: 15,0% %/total weight % / dry matter % wet capsule gellan 2.000% 13.33 1.482 Sorbitol 1.000% 6.67 0.741 Dextrin Cristal Tex 648 11.400% 76.00 8.445 Sodium citrate 0.200% 1.33 0.148 Citric acid 0.1% 0.67 0.074 unipure blue pigment CI77007 0.300% 2.00 0.222 Deionized water 85.000% 62.968 100.000% 100 Internal liquid phase % % Ethanol 5.0000% 5% Miglyol 812S 81.5000% 81.5% 22.245% Menthol codex 13.5000% 13.5% 3.685% 100.0000% 100.00% 100% WO 2007/012981 PCT/IB2006/002905 16 The obtained capsules are separated into two batches referred as Ala and Alb. Capsules from each batch are cooled at 4°C for 1h, washed with desionised water and then immersed in a bath containing an aqueous solution of calcium chloride (0.1% for Ala and 1% for Alb) at pH=3.5 at T=20°C during 15 minutes. Wet capsule crush strength (gel strength) is then measured for both capsules Ala and Alb using a texturometer TA.XT plus from Micro Stable System to compare influence of concentration of calcium (the results are presented on Figure 1). Wet capsule strength is higher using 1% CaCl2 solution than using 0.1% CaCl2 solution. After drying, crush strength of the capsules is measured using a texturometer in compression mode. 3039/A1a 3039/A1b Crush strength (dry capsules) 184g 186.6g The obtained capsules present the following physical characteristics: diameter: 2mm, thickness of the shell: 0.096mm, total weight: 4mg, weight of the core: 2.8mg (70%), weight of the shell: 1.2mg (30%). Such capsules are then placed into a clear toothgel and bring nice visual effect of spherical blue capsules liberating menthol when broken. WO 2007/012981 PCT/IB2006/002905 17 Example 2 Cinnamon Capsules (referenced as 4053/F1) are prepared by co-extruding an outer liquid phase and an internal liquid phase presenting the following compositions: Outer liquid phase Dry matter: 13.0% %/total weight % / dry matter gellan 2.000% 15.38% Sorbitol 1.900% 14.62% Dextrin Cristal Tex 648 8.500% 65.38% Sodium citrate 0.200% 1.54% Calcium citrate 0.100% 0.77% Titanium dioxide 0.300% 2.31% Osmosed water 87.000% 100% 100.000% Internal liquid phase %/total weight % without ethanol Ethanol 5,0000% Miglyol 812S 58.9000% 85,79% Cinnamon 19.6000% 14,21% Physcool 10.0000% 10.53% M-ethyl-p-menthane- 3-carboxamide commercialy available as WS3 6.5000% 6.84% Total 100,0000% 100/00% WO 2007/012981 PCT/IB2006/002905 18 The obtained capsules are cooled at 4°C for 1n, washed with deionised water and then immersed in a bath containing an aqueous solution containing 1.25% of calcium chloride at pH=3 at T=20°C during 30 minutes. The obtained capsules present the following physical characteristics: diameter: 1.2mm, thickness of the shell : 0.053mm, total weight : 0.87mg, weight of the core: 0.62mg (71.98%), weight of the shell : 0.24mg (2 8.02%), Capsules are then incorporated into a toothpaste base containing mint flavour and cinnamon capsules 4053/F1 at a 0.2% use level. During brushing, cinnamon flavour is clearly identified showing good breakability of the capsules. Example 3 Orange capsules (referred as 5053/C1) are prepared by coextruding an outer liquid phase and an internal liquid phase presenting the following compositions: Outer liquid phase Dry matter: 15.0% %/total weight % / wet capsule gellan 2.000% 0.95% Sorbitol 1.000% 0.45% Dextrin Cristal Tex 11.4% 5.36% WO 2007/012981 PCT/IB2006/002905 19 648 Sodium citrate 0.200% 0.01% water 84.5% 40% 100.000% Internal liquid phase % % Orange flavour 19.905% 5.47% Coconut oil 80% 47.7% Paprika color 0.095% 0.06% Total 100,0000% 100,00% Wet capsule crush strength (gel strength) is then measured using a texturometer TA.XT plus from Micro Stable System. Crushstrength value obtained is 15g and these capsules are easily broken under the teeth. The obtained capsules present the following physical characteristics: Diameter : 2.5 mm Thickness of the shell: 0.32 mm Total weight: 8.2 mg Capsules are then placed into a suspension of xanthan gum to be applied to beverage application. Capsules can be swallowed or broken under the teeth to liberate the flavour into the mouth. WO 2007/012981 PCT/IB2006/002905 20 Example 4 Menthol capsules (referred as 5025/B1) are prepared by coextruding an outer liquid phase and an internal liquid phase presenting the following composition: WO 2007/012981 PCT/IB2006/002905 21 Crush strength 94.31 g 5.09 g 15.09 g The treatment of wet capsules with an acid as calcium remleasing agent allow the enhancing of the crush strength of the capsules. WO 2007/012981 PCT/IB2006/002905 22 CLAIMS 1. A seamless breakable capsule comprising a core and a shell, wherein the shell includes a gelling agent comprising gellan gum alone or in combination with another gelling agent, a filler, and a divalent metal sequestering agent. 2. The seamless breakable capsule according to claim 1, wherein the gelling agent is a combination of gellan and one gelling agent selected from the group consisting of gelatin, agar, carrageenan, pectins, xanthan gum, cellulose gum, alginate, dextran, curdlan, welan gum, rhamsan gum or modified starches. 3 . The seamless breakable capsule according to claim 1 or 2, wherein the amount of gelling agent present in the shell is 4 to 95%, preferably 5 to 75%, even more preferably is 10 to 50% by weight of the total dry weight of the shell. 4. The seamless breakable capsule according to claim 3, wherein the gelling agent is gellan gum alone. 5. The seamless breakable capsule according to anyone of claims 1 to 3, wherein, when used in combination with at least another gelling agent, the weight ratio between gellan gum and the other gelling agent(s) is from 8 0/2 0 to 2 0/80, preferably 75/25 to 25/75, and even more preferably from 60/40 to 50/50. 6. The seamless breakable capsule according to anyone of claims 1 to 5, wherein the filler is a starch derivative such as dextrin, maltodextrin, cyclodextrin and/or a cellulose derivative such as hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose WO 2007/012981 PCT/IB2006/002905 23 (HPC), methylcellulose (MC), polyvinyl alcohols, polyols or mixtures thereof. 7. The seamless breakable capsule according to anyone of claims 1 to 6, wherein the amount of the filler in the shell is at most 98.5%, preferably from 25 to 95% and even more preferably from 50 to 80% by weight on the total dry weight of the shell. 8. The seamless breakable capsule according to anyone of claims 1 to 7, wherein the sequestering agent is a metal salt, preferably selected from the group consisting of trisodium citrate, trisodium phosphate, tetrasodium pyrophosphate, sodium hexametaphosphate and mixtures thereof. 9. The seamless breakable capsule according to anyone of claims 1 to 8, wherein the amount of sequestering agent is at most 2%, preferably at most 1% and even more preferably at most 0.5% by weight of the total dry weight of the shell. 10. The seamless breakable capsule according to anyone of claims 1 to 9, wherein the shell further comprises an acid salt selected from the group comprising such as citrate, glucuronate, adipate, fumarate, gluconate and salt of glucono-delta-lactone, and mixtures thereof. 11. The seamless breakable capsule according to anyone of claims 1 to 10, having an crush strength from 0.01 to 5 kp. 12. The seamless breakable capsule according to anyone of claims 1 to 11, wherein the amount of plasticizer ranges from 0.1 to 30% by weight, preferably from 2% to 15% WO 2007/012981 PCT/IB2006/002905 24 by weight and even more preferably from 3 to 10% by weight of the total dry weight of the shell. 13. The seamless breakable capsule according to anyone of claims 1 to 12, having an crush strength from 0.01 to 5 kp. 14. A process for manufacturing a seamless breakable capsule, comprising - co-extruding an external and hydrophilic liquid phase, and an internal and lipophilic liquid phase, in order to form a capsule constituted of a core comprising the internal and lipophilic phase, and a shell comprising the external and hydrophilic phase, - immersing into an aqueous solution containing a curing agent, wherein the external liquid phase includes a gelling agent comprising gellan gum alone or in combination with another gelling agent, a filler, and a divalent metal sequestering agent. 15. The process for manufacturing a seamless breakable capsule according to claim 14, comprising: - co-extruding an external and hydrophilic liquid phase, and an internal and lipophilic liquid phase, in order to form a capsule constituted of a core comprising the internal and lipophilic phase and a shell comprising the external and hydrophilic phase, optionally solidifying and/or gelling the surface of the shell by keeping the capsule under cold conditions, - optionally washing the so-obtained capsule with an organic solvent, WO 2007/012981 PCT/IB2006/002905 25 - immersing into an aqueous solution containing a curing agent. - optionally drying the capsule. 16. The process for manufacturing a seamless breakable capsule according to claim 14 or 15, wherein the curing agent comprises divalent ions, preferably calcium ions. 17. The process for manufacturing a seamless breakable capsule according to anyone of claims 14 to 16, wherein the aqueous solution containing a curing agent is a calcium chloride solution, which pH is preferably of 3 to 4. 18. The process for manufacturing a seamless breakable capsule according to anyone of claims 14 to 17, wherein the gelling agent is a combination of gellan and at least one other gelling agent selected from the group consisting of gelatin and hydrocolloids such as agar, carragheenan, pectins, xanthan gum, cellulose gum, alginate, dextran, curdlan, welan gum, rhamsan gum or modified starches, and mixtures thereof. 19. The process for manufacturing a seamless breakable capsule according to anyone of claims 14 to 18, wherein the filler is a starch derivative such as dextrin, maltodextrin, cyclodextrin, a cellulose derivative such as HPMC, HPC, MC and mixtures thereof. 20. The process for manufacturing a seamless breakable capsule according to anyone of claims 14 to 19, wherein the sequestering agent is a metal salt, preferably selected from the group comprising sodium carbonate, trisodium citrate, trisodium phosphate, tetrasodium WO 2007/012981 PCT/IB2006/002905 26 pyrophosphate, sodium hexametaphosphate and mixtures thereof. 21. The process for manufacturing a seamless breakable capsule according to anyone of claims 14 to 20, wherein the external hydrophilic liquid phase further comprises a plasticizer, preferably selected from the group consisting of glycerol, sorbitol, maltitol, triacetine or PEG type, or another polyol with plasticizing properties, and mixtures thereof. 22. Slurry containing breakable capsules according to anyone of claims 1 to 13, in suspension in a gel formed with a gel forming agent such CMC, xanthan gum, or Carbopol, and optionally comprising preservatives and stabilizers. 23. Food product including breakable capsules according to anyone of claims 1 to 13. 24. Oral care product including breakable capsules according to anyone of claims 1 to 13. 25. Pharmaceutical product including breakable capsules according to anyone of claims 1 to 13. 26. Fragrance including breakable capsules according to anyone of claims 1 to 13. The invention relates to a process for manufacturing a seamless breakable capsule, comprising - co-extruding an external and hydrophilic liquid phase, and an internal and lipophilic liquid phase, in order to form a capsule constituted of a core comprising then internal and lipophilic phase, and a shell comprising the external and hydrophilic phase, - immersing into an aqueous solution containing a curing agent, wherein the external liquid phase includes a gelling agent comprising gellan gum alone or in combination with another gelling agent, a filler, and a divalent metal sequestering agent, and to breakable capsules comprising a core and a shell, wherein the shell includes a gelling agent comprising gellan gum alone or in combination with another gelling agent, a filler, and a divalent metal sequestering agent.

Full Text

WO 2007/012981 PCT/IB2006/002905
1
GELLAN SEAMLESS BREAKABLE CAPSULE AND PROCESS FOR
MANUFACTURING THEREOF.
The present invention relates to a breakable
capsule having a fluid core and a solid or fluid breakable
shell.
In this invention, the term "capsule" means a
spherical or substantially spherical delivery system of a
substance, said substance being hereinafter referred to as
"the core", and said substance being encapsulated into a
shell, the shell being breakable and releasing the core
when broken or ruptured. The term fluid means flowing as
opposed to being in a solid state. According to the
invention, the term fluid includes finely divided solids,
such as a powder, and also gel, or any physical state of a
product wherein said product changes shape or direction
uniformly, in response to an external force imposed upon
it. According to the invention, fluid preferably refers to
a flowable or gellified product.
The term "breakable capsule" refers to a capsule
as hereabove defined, wherein the shell can be ruptured by
means of a pressure, which results in the release of the
core. According to an embodiment, the capsule of the
invention may be specifically designed to be incorporated
into a fluid medium such as for example a gel, a pasty or a
liquid medium containing water; in this embodiment, the
capsules may be suspended or mixed by any suitable means in
order to bring an visual effect of homogeneous dispersion
of the capsules in the medium; advantageously, the shell
and/or the core of the capsule is coloured. According to
another embodiment, the capsule of the invention is

WO 2007/012981 PCT/IB2006/002905
2
dispersed into a solid or fluid medium, such as for example
a powder; advantageously, the shell and/or the core of the
capsule is coloured.
Such capsules are useful for numerous applications,
such as in oral care application (toothpaste, mouthwash,
gums...) , in food applications such as confectionary, dairy,
bakery, savory, in neutraceutical applications or in
pharmaceutical or in personal care products such as
cosmetic products and the like.
In the present patent application, the term
"capsule" will be used to designate any size of capsules,
including macrocapsules and microcapsules and preferably
capsule which larger diameter is from 0.5 mm up to 8 mm,
preferably 1 to 5 mm; more preferably 1.2 to 3 mm.
It is of particular interest to obtain seamless
capsules, as the breakability of a welded capsule (also
designated in the prior art as softgel or hard capsule) may
be influenced by the easy or unwanted rupture of the weld.
Fuji patent application JP10291928 describes a
capsule obtained through a co-extrusion process, wherein
the external liquid phase comprises gellan and calcium
salts. Gellan gum, first discovered in 1978, is produced by
the microorganism Sphingomonas elodea.
The Applicant has found that the production of
gellan capsule through the Fuj i process was not
satisfactory and resulted in poor quality capsules and in
processing difficulties, because the gellan was actually
gelling during the co-extrusion, and it was not possible to
obtain spherical and homogeneous breakable capsules.

WO 2007/012981 PCT/IB2006/002905
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For this reason, the Applicant tried to improve the
Fuji process and found that the drawbacks of the prior art
process may be due to the presence of calcium salts, and
more generally to divalent metal salts in gellan during the
co-extrusion step. Thus, the Applicant carried out a
process wherein the co-extrusion liquid phase containing
gellan was performed in absence of calcium salts, and
observed that, surprisingly, the resulting capsules had the
required spherical or substantially spherical shape and
homogeneous sizes. However, the capsules thus obtained
could not be used as such, because the shell was too soft
and the resulting capsules were not breakable capsules; the
Applicant found a solution to this subsequent technical
problem by contacting the capsules with divalent metal
ions, preferably calcium or magnesium ions, or by using
organic acid solution, once the co-extrusion process is
finished, and this finally lead to satisfactory breakable
capsules.
Thus, this invention relates to a process for
manufacturing seamless breakable capsules and to new
seamless breakable capsules.
The process of the invention comprises a step (A)
of co-extrusion of an external and hydrophilic liquid phase
and an internal and lipophilic liquid phase, in order to
form a capsule having a core comprising the internal and
lipophilic phase and a shell comprising the external and
hydrophilic phase; and a step (B) of washing and immersing
the capsules into an aqueous solution preferably containing
a curing agent, the curing agent being one of the means for
making the shell breakable as required for the intended
use; optionally a step (C) of drying the obtained capsules

WO 2007/012981 PGT/IB2006/002905
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or optionally a step (D) of suspending the capsules into an
fluid medium.
The co-extrusion process comprises three main
stages: compound drop formation, shell solidification and
capsule collection. The compound drop is a sphere of the
liquid fill phase inside the shell phase. The liquid fill
phase is hereinafter referred to as "the core". The shell
phase is hereinafter referred to as "the shell".
According to the invention, the external liquid
phase includes a gelling agent comprising gellan gum, alone
or in combination with at least one suitable gelling agent,
a filler, and a metal sequestering agent, the liquid
preferably being aqueous, more preferably the liquid is
water, preferably desionized or osmozed water.
By "gelling agent" in the meaning of this
invention, it is referred to an agent able to convert an
aqueous phase from a flowable or fluid liquid to a solid or
a gel.
By "sequestering agent" in the meaning of this
invention it is referred to any agent complexing, chelating
or sequestering bivalent ions such as calcium or magnesium
ions.
The term "substantially", when referring to a
number or value, means + or - 10 % of the value; when
referring to a sphere, it means a distorted sphere which
larger diameter is + or - 10 % of the diameter of the
expected sphere.
The term "wet capsule" in the meaning of this
invention, refers to a capsule which shell includes a
positive amount of water. The term wet capsule is used for
the calculation of percentages of ingredients in the final

WO 2007/012981 PCT/IB2006/002905
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product or shell, as opposed to the calculation based on
the dry weight of said final product or shell.
The breakable capsule according to the invention
preferably has a crush strength from 0.01 to 5 kp,
preferably from 0.1 to 2.5 kp, edge values being included.
The crush strength of the capsule is measured by
continuously applying a load vertically onto one particle
until rupture. The crush strength of the capsules in the
present invention is measured by using a texturometer TA.XT
plus from Micro Stable System in compression mode or a
LLOYD - CHATILLON Digital Force Gauge, Model DFIS 50,
having a capacity of 25Kg, a resolution of 0.02 Kg, and an
accuracy of +/- 0,15 %. The force gauge is attached to a
stand; the capsule is positioned in the middle of a plate
that is moved up with a manual thread screw device.
Pressure is then applied manually and the gauge records the
maximum force applied at the very moment of the rupture of
the capsule, (measured in Kg or in Lb) . Rupture of the
capsule results in the release of the core.
Gellan gum is a hydrocolloid which, according to
the invention, can be used as the sole gelling agent of the
external liquid phase, or in combination with at least one
ohter gelling agent. Other suitable gelling agents may be
alginates, agar, carragheenan, pectines, xanthan gum,
Arabic gum, tara gum, ghatti gum, karaya gum, dextran,
curdlan, welan gum, rhamsan gum or modified starches.
Suitable gellan gums are for example, but not limited to
deacylated gellan gum. Kelcogel® can be mentioned as a
suitable gellan gum.
The amount of gelling agent present in the shell
is 4 to 95%, preferably 5 to 75%, even more preferably is

WO 2007/012981 PCT/IB2006/002905
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10 to 50%, more preferably 12 to 40 % by weight of the
total dry weight of the shell.
When used in combination with at least another
gelling agent, the weight ratio between gellan gum and the
other gelling agent(s) is from 80/20 to 20/80, preferably
75/25 to 25/75, and even more preferably from 60/40 to
50/50.
Preferably, the weight ratio of gelling agent /
dried shell is greater than 10%, preferably greater than
12, more preferably greater than 15%.
The filler is any suitable material that can
increase the percentage of dry material in the external
liquid phase or bring filming properties. Increasing the
dry material amount in a shell results in solidifying the
shell, and in making it physically more resistant or
impermeable. Preferably, the filler is selected from the
group comprising starch derivatives such as dextrin,
maltodextrin, polyol, cyclodextrin (alpha, beta or gamma),
or cellulose derivatives such as
hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose
(HPC), methylcellulose (MC), carboxymethylcellulose (CMC),
polyethylene glycol derivatives, polyvinyl alcohol, polyols
or mixture thereof.
The amount of filler in the shell is at most
98.5%, preferably from 25 to 95% and even more preferably
from 50 to 80% by weight on the total dry weight of the
shell.
Using a divalent metal sequestering or complexing
agent allows trapping the divalent metal ions which are
possibly present in the components of the liquid phase
including water and which have a gelling effect on gellan.
Thus, the use of a divalent metal sequestering agent,

WO 2007/012981 PCT/IB2006/002905
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preferably of a calcium ion sequestering agent, allows the
gellan to be co-extruded without undesirable or
uncontrollable gelling during the co-extrusion.
The amount of sequestering agent is at most 2%,
preferably at most 1% and even more preferably at most 0.5%
by weight of the total dry weight of the shell.
Preferably, the water used for the external phase
is deionized water and/or osmozed water; using processing
water remains possible but needs adjusting the amount of
divalent metal sequestering agent.
The sequestering agent is a metal salt,
preferably selected from the group comprising trisodium
citrate, trisodium phosphate, tetrasodium pyrophosphate,
sodium hexametaphosphate and mixtures thereof.
The hydrophilic external liquid phase may further
comprise at least one plasticizer, which may be at least
one of glycerol, sorbitol, maltitol, triacetine or
polyethylene glycol type product, or a polyalcohol with
plasticizing or humectant properties. Advantageously, the
hydrophilic external liquid phase further comprises at
least one colouring agent or pigment; according to a first
embodiment, the colouring agent or the pigment is in a form
of a powder or a suspension stable in an aqueous medium.
According to another embodiment of the invention, the
liquid phase may include perfumes, aromas, fragrances or
any odoring agent.
According to one embodiment of the invention, the
co-extrusion step (A) of the process can be performed at a
temperature being from room temperature to 100°C.
Advantageously, it is performed at room temperature, which
means between 18 and 30°C, preferably 20-25 °C under
atmospheric pressure.

WO 2007/012981 PCT/IB2006/002905
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The co-extrusion step is a synchronous extrusion
of two liquids: the external and hydrophilic liquid phase,
and the internal and lipophilic liquid phase which can be
performed using an apparatus and a process as described in
EP 513603, the disclosure of which is herein incorporated
by reference.
According to an embodiment of the invention,
after the co-extrusion step (A), the solidification step is
performed by keeping cold the capsules in order to ensure
correct gelling of the shell, for example by contacting
them with a cold bath. The cold bath may preferably be cold
oil or cold emulsion. Cold means any temperature below
18"°C, preferably the temperature is from 2 to 10 °C, more
preferably 4 to 6 °C.
According to an embodiment of the invention, the
capsules may then be centrifuged in order to remove the
surplus oil, and/or washed with organic solvent (such as
acetone, ethyl acetate, ethanol, petroleum ether, etc.)
also to remove the surplus oil, and optionally dried in a
air flow at controlled temperature and humidity. The
relative humidity of the drying air is 20% to 60%,
preferably 3 0 to 50%; the temperature of the drying air is
of 15 to 60 °C, preferably 35 to 45 °C.
According to another embodiment, the capsules
are preferably immersed into an aqueous solution or an
emulsion containing a curing agent which comprises a
divalent salt and optionally an acid. The effect of the
immersion step is to wash out the oil remaining at the
periphery of the capsule, and to gradually strengthen the
shell, notably through dehydration and osmotic equilibrium.
According to one embodiment of the invention,
after immersion, the capsules are dried in the same

WO 2007/012981 PCT/IB2006/002905
9
conditions as mentioned above. According to another
embodiment of the invention, after immersion, the capsules
are not dried.
The curing agent preferably comprises divalent
metal ions, or a mixture of divalent metal ions, such as
calcium ions or magnesium ions.
The aqueous solution or emulsion containing the
curing agent is preferably a divalent metal salt solution,
preferably containing calcium or magnesium salts, more
preferably, calcium dichloride, calcium carbonate, calcium
sulfate or dicalcium phosphate. This solution may be the
aqueous phase of an oil-in-water emulsion. This solution
can be at a temperature comprised between 2°C and room
temperature. Advantageously, the aqueous solution
containing the curing agent is maintained under acid
conditions of pH, and preferably at a pH less than 5, more
preferably from 2 to 4. According to a preferred embodiment
of the invention, the aqueous solution or emulsion
containing a curing agent is a calcium chloride solution
having a pH of 3 to 4.
The aqueous solution containing the curing agent
can also contain preservatives or bactericides such as
benzoate, parabens, diols, cetylpyridinium chloride,
diazolidinyl urea or any preservatives used for food,
pharmaceutical or cosmetic products.
According to one embodiment of the invention, the
process comprises the steps of co-extruding the above
mentioned external and internal liquid phases, optionally
solidifying and/or gelling the surface of the shell by
keeping the capsule under cold conditions, as explained
herein above, optionally centrifugating, optionally washing

WO 2007/012981 PCT/IB2006/002905
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the so-obtained capsules with an organic solvent, immersing
the resulting capsules into an aqueous solution containing
a curing agent, and optionally drying the capsules.
According to one embodiment of the invention, the
solidifying/gelling/curing steps can be gathered into a
single step, for example by dipping the capsules into a
bath, under cold conditions, containing the divalent metal
salts, preferably calcium or magnesium salts, more
preferably, calcium dichloride, calcium sulfate or
dicalcium phosphate. This bath may be an oil-in-water
emulsion.
The capsules manufactured through the process
according to the invention are substantially or perfectly
spherical and very homogeneous in size.
This invention also relates to breakable capsules
which are preferably seamless capsules susceptible to be
obtained through the process according to the invention.
The capsule of the invention comprises a core and a
shell, and said shell includes a gelling agent comprising
gellan gum alone or in combination with another gelling
agent, a filler, and a divalent metal sequestering agent.
Preferably the gelling agent of the shell is a
combination of gellan and of at least one other gelling
agent selected from the group consisting of gelatin and
hydrocolloids such as agar, carragheenan, pectins, xanthan
gum, alginate, tara gum, arabic gum, ghatti gum, caroub
gum, cellulose gum, dextran, curdlan, welan gum, rhamsan
gum or modified starches.
According to a preferred embodiment of the
invention the filler and the sequestering agent, are as
described hereinabove.

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According to another embodiment, the shell further
comprises a plasticizer as described hereinabove.
The amount of plasticizer ranges from 0.1% to 30%
by weight, preferably from 2% to 15% by weight, and even
more preferably from 3 to 10% by weight of the total dry
weight of the shell.
According to the intended use of said capsules, the
shell may contain other additives such as perfumes, aromas,
or any flavoring agent.
According to the intended use of said capsule, the
shell may comprise coloring agent such as pigments,
titanium dioxide, iron oxides, carbon black, or any type of
food, oral care, cosmetic or pharmaceutical pigment such as
Covasorb colors distributed by LCW.
The shell of a breakable capsule according to
the invention represents by weight 8 to 50% of the total
weight of said capsule, preferably 10 to 40%, more
preferably 20 to 3 0%.
The amount of water present in the shell is of
1 to 60 %, preferably 5 to 40 % the capsule remaining
breakable even at the higher percentages.
According to a preferred embodiment, the breakable
capsule according to the invention has a crush strength of
from 0.01 to 5, preferably from 0.01 to 2.5 kp.
Advantageously, the shell thickness of the
capsule is 10-500 microns, preferably 30-150 microns, more
preferably 50-60 microns. The ratio diameter of the

WO 2007/012981 PCT/IB2006/002905
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capsule/thickness of the shell is in the range of 1 to 100,
preferably 5 to 30.
The core of the capsule is preferentially
composed of a mixture of materials or products which are
lipophilic or partially soluble in ethanol, or of molecules
formulated as oil/water/oil emulsions.
The core of a breakable capsule according to
the invention represents by weight 50 to 92% of the total
weight of said capsule, preferably 60 to 90%, more
preferably 70 to 80%.
The core of the capsule may be composed of one
or more lipophilic solvents conventionally used in the
food, pharmaceutical or cosmetic industries. In a preferred
embodiment, these lipophilic solvents may be triglycerides,
especially medium chain triglycerides, and in particular
triglycerides of caprylic and capric acid, or mixtures of
triglycerides such as vegetable oil, hydrogenated oil,
coconut oil, palm oil, olive oil, sunflower oil, corn oil,
linseed oil, cottonseed oil, groundnut oil, grape seed oil,
wheat germ oil, fish oil, beet fat, mineral oils and
silicone oils. The amount of lipophilic solvent in the core
of a capsule according to the invention is of the order of
0.01 to 90%, preferentially 25 to 75%, of the total weight
of the capsule.
The core may also comprise one or more aromatic
or fragrance molecules as conventionally used in the
formulation of flavoring or fragrance compositions. Mention
will in particular be made of aromatic, terpenic and/or
sesquiterpenic hydrocarbons, and more particularly
essential oils, alcohols, aldehydes, phenols, carboxylic
acids in their various forms, aromatic acetals and ethers,

WO 2007/012981 PCT/IB2006/002905
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nitrogenous heterocycles, ketones, sulfides, disulfides and
mercaptans which may be aromatic or non aromatic. It may
also comprise one or more molecules or extracts for
cosmetic use.
The core may also comprise one or more fillers
as used in aromatic emulsions. Mention will be made of
dammar gum, wood resins of the ester gum type, sucrose
acetate isobutyrate (SAIB) or brominated vegetable oils.
The function of these weighting agents is to adjust the
density of the liquid core.
The core may also comprise one or more
sweeteners, which may be provided in the form of a solution
or suspension in ethanol. Examples of suitable sweeteners
may be, but is not limited to, aspartame, saccharine, NHDC,
sucralose, acesulfame, neotame, thaumatin, steviosides,
etc.
The core may also comprise one or more "sensate"
aromatic agents, which provide either a freshening effect
or a hot effect in the mouth. Suitable freshening agents
may be, but are not limited to, menthyl succinate and
derivatives thereof, in particular Physcool® marketed by
the Applicant. A suitable hot effect agent may be, but is
not limited to, vanillyl ethyl ether.
The flavoring agents that can be solubilized in
the solvent of the core of the capsule include, but are not
limited to, natural or synthetic aromas and/or fragrances.
Examples of suitable fragrances are fruity, confectionery,
floral, sweet, woody fragrances. Examples of suitable
aromas are vanilla, coffee, chocolate, cinnamon, mint. The
core may also comprise a lipophilic color such as fake
colors but also natural colors such as paprika oleoresin,

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turmeric oleoresin, carotenes, chlorophyllin, or any other
suitable natural coloring product. The core may also
include lipophilic active agents, such as vitamins, more
preferably vitamine B; fatty acids, preferably omega 3 and
natural extracts of plants.
The capsules according to the invention can be
included in various products, such as food products, oral
care products, nutraceutical products, pharmaceutical
products, cleaning products and cosmetic products. The
invention thus relates to a food product including
breakable capsules according to the invention; an oral care
product including breakable capsules according to the
invention, preferably a toothpaste including breakable
capsules according to the invention; a pharmaceutical
product including breakable capsules according to the
invention; a fragrance including breakable capsules
according to the invention.
The capsules of the invention may be within a
slurry, in suspension in a gel, preferably carried out with
a gel forming agent such as xanthan gum, gellan gum, CMC or
Carbopol, araboxymethyl cellulose, or any polymer commonly
used as suspending agent and optionally comprising
preservatives and stabilizers.
The total weight of the capsule of the invention
depends on its diameter and on the amount of core filling
the shell. According to an embodiment of the invention, the
total weight of the capsule is within the range of 0.1 to
50 mg, preferably 0.2 to 20 mg, more preferably 0.5 to 10
mg.

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The invention is hereunder illustrated by the
following examples, which should not be considered as
limiting the scope of the invention.
EXAMPLES
Example 1
Menthol Capsules (referred as 3039/A1) are prepared by co-
extruding an outer liquid phase and an internal liquid
phase presenting the following compositions:

Outer liquid phase
Dry matter: 15,0% %/total
weight % / dry
matter % wet
capsule
gellan 2.000% 13.33 1.482
Sorbitol 1.000% 6.67 0.741
Dextrin Cristal Tex
648 11.400% 76.00 8.445
Sodium citrate 0.200% 1.33 0.148
Citric acid 0.1% 0.67 0.074
unipure blue
pigment CI77007 0.300% 2.00 0.222
Deionized water 85.000% 62.968
100.000% 100

Internal liquid
phase % %
Ethanol 5.0000% 5%
Miglyol 812S 81.5000% 81.5% 22.245%
Menthol codex 13.5000% 13.5% 3.685%
100.0000% 100.00% 100%

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The obtained capsules are separated into two batches
referred as Ala and Alb. Capsules from each batch are
cooled at 4°C for 1h, washed with desionised water and then
immersed in a bath containing an aqueous solution of
calcium chloride (0.1% for Ala and 1% for Alb) at pH=3.5 at
T=20°C during 15 minutes.
Wet capsule crush strength (gel strength) is then
measured for both capsules Ala and Alb using a texturometer
TA.XT plus from Micro Stable System to compare influence of
concentration of calcium (the results are presented on
Figure 1).
Wet capsule strength is higher using 1% CaCl2 solution
than using 0.1% CaCl2 solution.
After drying, crush strength of the capsules is
measured using a texturometer in compression mode.

3039/A1a 3039/A1b
Crush strength
(dry capsules) 184g 186.6g
The obtained capsules present the following physical
characteristics:
diameter: 2mm,
thickness of the shell: 0.096mm,
total weight: 4mg,
weight of the core: 2.8mg (70%),
weight of the shell: 1.2mg (30%).
Such capsules are then placed into a clear
toothgel and bring nice visual effect of spherical blue
capsules liberating menthol when broken.

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Example 2
Cinnamon Capsules (referenced as 4053/F1) are prepared by
co-extruding an outer liquid phase and an internal liquid
phase presenting the following compositions:

Outer liquid phase
Dry matter: 13.0% %/total
weight % / dry
matter
gellan 2.000% 15.38%
Sorbitol 1.900% 14.62%
Dextrin Cristal Tex
648 8.500% 65.38%
Sodium citrate 0.200% 1.54%
Calcium citrate 0.100% 0.77%
Titanium dioxide 0.300% 2.31%
Osmosed water 87.000% 100%
100.000%
Internal liquid
phase %/total
weight % without
ethanol
Ethanol 5,0000%
Miglyol 812S 58.9000% 85,79%
Cinnamon 19.6000% 14,21%
Physcool 10.0000% 10.53%
M-ethyl-p-menthane-
3-carboxamide
commercialy
available as WS3 6.5000% 6.84%
Total 100,0000% 100/00%

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The obtained capsules are cooled at 4°C for 1n, washed with
deionised water and then immersed in a bath containing an
aqueous solution containing 1.25% of calcium chloride at
pH=3 at T=20°C during 30 minutes.
The obtained capsules present the following physical
characteristics:
diameter: 1.2mm,
thickness of the shell : 0.053mm,
total weight : 0.87mg,
weight of the core: 0.62mg (71.98%),
weight of the shell : 0.24mg (2 8.02%),
Capsules are then incorporated into a toothpaste base
containing mint flavour and cinnamon capsules 4053/F1 at a
0.2% use level. During brushing, cinnamon flavour is
clearly identified showing good breakability of the
capsules.
Example 3
Orange capsules (referred as 5053/C1) are prepared by
coextruding an outer liquid phase and an internal liquid
phase presenting the following compositions:

Outer liquid phase
Dry matter: 15.0% %/total
weight % / wet
capsule
gellan 2.000% 0.95%
Sorbitol 1.000% 0.45%
Dextrin Cristal Tex 11.4% 5.36%

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648
Sodium citrate 0.200% 0.01%
water 84.5% 40%
100.000%
Internal liquid
phase % %
Orange flavour 19.905% 5.47%
Coconut oil 80% 47.7%
Paprika color 0.095% 0.06%
Total 100,0000% 100,00%

Wet capsule crush strength (gel strength) is then measured
using a texturometer TA.XT plus from Micro Stable System.
Crushstrength value obtained is 15g and these capsules are
easily broken under the teeth.
The obtained capsules present the following physical
characteristics:
Diameter : 2.5 mm
Thickness of the shell: 0.32 mm
Total weight: 8.2 mg
Capsules are then placed into a suspension of xanthan gum
to be applied to beverage application. Capsules can be
swallowed or broken under the teeth to liberate the flavour
into the mouth.

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20
Example 4
Menthol capsules (referred as 5025/B1) are prepared by
coextruding an outer liquid phase and an internal liquid
phase presenting the following composition:

WO 2007/012981 PCT/IB2006/002905
21

Crush
strength 94.31 g 5.09 g 15.09 g
The treatment of wet capsules with an acid as calcium
remleasing agent allow the enhancing of the crush strength
of the capsules.

WO 2007/012981 PCT/IB2006/002905
22
CLAIMS
1. A seamless breakable capsule comprising a core
and a shell, wherein the shell includes a gelling agent
comprising gellan gum alone or in combination with another
gelling agent, a filler, and a divalent metal sequestering
agent.
2. The seamless breakable capsule according to
claim 1, wherein the gelling agent is a combination of
gellan and one gelling agent selected from the group
consisting of gelatin, agar, carrageenan, pectins, xanthan
gum, cellulose gum, alginate, dextran, curdlan, welan gum,
rhamsan gum or modified starches.
3 . The seamless breakable capsule according to claim
1 or 2, wherein the amount of gelling agent present in the
shell is 4 to 95%, preferably 5 to 75%, even more
preferably is 10 to 50% by weight of the total dry weight
of the shell.
4. The seamless breakable capsule according to claim
3, wherein the gelling agent is gellan gum alone.
5. The seamless breakable capsule according to
anyone of claims 1 to 3, wherein, when used in combination
with at least another gelling agent, the weight ratio
between gellan gum and the other gelling agent(s) is from
8 0/2 0 to 2 0/80, preferably 75/25 to 25/75, and even more
preferably from 60/40 to 50/50.
6. The seamless breakable capsule according to
anyone of claims 1 to 5, wherein the filler is a starch
derivative such as dextrin, maltodextrin, cyclodextrin
and/or a cellulose derivative such as
hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose

WO 2007/012981 PCT/IB2006/002905
23
(HPC), methylcellulose (MC), polyvinyl alcohols, polyols or
mixtures thereof.
7. The seamless breakable capsule according to anyone
of claims 1 to 6, wherein the amount of the filler in the
shell is at most 98.5%, preferably from 25 to 95% and even
more preferably from 50 to 80% by weight on the total dry
weight of the shell.
8. The seamless breakable capsule according to
anyone of claims 1 to 7, wherein the sequestering agent is
a metal salt, preferably selected from the group consisting
of trisodium citrate, trisodium phosphate, tetrasodium
pyrophosphate, sodium hexametaphosphate and mixtures
thereof.
9. The seamless breakable capsule according to
anyone of claims 1 to 8, wherein the amount of sequestering
agent is at most 2%, preferably at most 1% and even more
preferably at most 0.5% by weight of the total dry weight
of the shell.
10. The seamless breakable capsule according to
anyone of claims 1 to 9, wherein the shell further
comprises an acid salt selected from the group comprising
such as citrate, glucuronate, adipate, fumarate, gluconate
and salt of glucono-delta-lactone, and mixtures thereof.
11. The seamless breakable capsule according to
anyone of claims 1 to 10, having an crush strength from
0.01 to 5 kp.
12. The seamless breakable capsule according to
anyone of claims 1 to 11, wherein the amount of plasticizer
ranges from 0.1 to 30% by weight, preferably from 2% to 15%

WO 2007/012981 PCT/IB2006/002905
24
by weight and even more preferably from 3 to 10% by weight
of the total dry weight of the shell.
13. The seamless breakable capsule according to
anyone of claims 1 to 12, having an crush strength from
0.01 to 5 kp.
14. A process for manufacturing a seamless
breakable capsule, comprising
- co-extruding an external and hydrophilic liquid
phase, and an internal and lipophilic liquid phase, in
order to form a capsule constituted of a core comprising
the internal and lipophilic phase, and a shell comprising
the external and hydrophilic phase,
- immersing into an aqueous solution containing
a curing agent,
wherein the external liquid phase includes a
gelling agent comprising gellan gum alone or in combination
with another gelling agent, a filler, and a divalent metal
sequestering agent.
15. The process for manufacturing a seamless
breakable capsule according to claim 14, comprising:
- co-extruding an external and hydrophilic liquid
phase, and an internal and lipophilic liquid phase, in
order to form a capsule constituted of a core comprising
the internal and lipophilic phase and a shell comprising
the external and hydrophilic phase,
optionally solidifying and/or gelling the
surface of the shell by keeping the capsule under cold
conditions,
- optionally washing the so-obtained capsule with
an organic solvent,

WO 2007/012981 PCT/IB2006/002905
25
- immersing into an aqueous solution containing
a curing agent.
- optionally drying the capsule.
16. The process for manufacturing a seamless
breakable capsule according to claim 14 or 15, wherein the
curing agent comprises divalent ions, preferably calcium
ions.
17. The process for manufacturing a seamless
breakable capsule according to anyone of claims 14 to 16,
wherein the aqueous solution containing a curing agent is a
calcium chloride solution, which pH is preferably of 3 to
4.
18. The process for manufacturing a seamless
breakable capsule according to anyone of claims 14 to 17,
wherein the gelling agent is a combination of gellan and at
least one other gelling agent selected from the group
consisting of gelatin and hydrocolloids such as agar,
carragheenan, pectins, xanthan gum, cellulose gum,
alginate, dextran, curdlan, welan gum, rhamsan gum or
modified starches, and mixtures thereof.
19. The process for manufacturing a seamless
breakable capsule according to anyone of claims 14 to 18,
wherein the filler is a starch derivative such as dextrin,
maltodextrin, cyclodextrin, a cellulose derivative such as
HPMC, HPC, MC and mixtures thereof.
20. The process for manufacturing a seamless
breakable capsule according to anyone of claims 14 to 19,
wherein the sequestering agent is a metal salt, preferably
selected from the group comprising sodium carbonate,
trisodium citrate, trisodium phosphate, tetrasodium

WO 2007/012981 PCT/IB2006/002905
26
pyrophosphate, sodium hexametaphosphate and mixtures
thereof.
21. The process for manufacturing a seamless
breakable capsule according to anyone of claims 14 to 20,
wherein the external hydrophilic liquid phase further
comprises a plasticizer, preferably selected from the group
consisting of glycerol, sorbitol, maltitol, triacetine or
PEG type, or another polyol with plasticizing properties,
and mixtures thereof.
22. Slurry containing breakable capsules
according to anyone of claims 1 to 13, in suspension in a
gel formed with a gel forming agent such CMC, xanthan gum,
or Carbopol, and optionally comprising preservatives and
stabilizers.
23. Food product including breakable capsules
according to anyone of claims 1 to 13.
24. Oral care product including breakable
capsules according to anyone of claims 1 to 13.
25. Pharmaceutical product including breakable
capsules according to anyone of claims 1 to 13.
26. Fragrance including breakable capsules
according to anyone of claims 1 to 13.

The invention relates to a process for manufacturing a seamless breakable capsule,
comprising - co-extruding an external and hydrophilic liquid phase, and an internal and
lipophilic liquid phase, in order to form a capsule constituted of a core comprising then
internal and lipophilic phase, and a shell comprising the external and hydrophilic phase,
- immersing into an aqueous solution containing a curing agent, wherein the external
liquid phase includes a gelling agent comprising gellan gum alone or in combination
with another gelling agent, a filler, and a divalent metal sequestering agent, and to
breakable capsules comprising a core and a shell, wherein the shell includes a gelling
agent comprising gellan gum alone or in combination with another gelling agent, a filler,
and a divalent metal sequestering agent.

Documents:

http://ipindiaonline.gov.in/patentsearch/GrantedSearch/viewdoc.aspx?id=Qh9It5aFjJmSONH26WPUqw==&loc=wDBSZCsAt7zoiVrqcFJsRw==

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Patent Number

272140

Indian Patent Application Number

4809/KOLNP/2007

PG Journal Number

13/2016

Publication Date

25-Mar-2016

Grant Date

18-Mar-2016

Date of Filing

11-Dec-2007

Name of Patentee

V. MANE FILS

Applicant Address

620, ROUTE DE GRASSE 06620 BAR SUR LOUP

Inventors:

#	Inventor's Name	Inventor's Address
1	HARTMANN DIDIER	83 AVENUE MAURICE CHEVALIER RÉSIDENCE LA BOISSIÈRE BÂT BAMBOU 06150 CANNES LA BOCCA
2	HANNETEL JEAN-MICHEL	6 RUE JEANNE JUGAN 06130 GRASSE
3	COURSIERES NATHALIE	580 CHEMIN DE LA STÈLE 06530 ST CEZAIRE SUR SIAGNE
4	MANE JEAN	DOMAINE SAINT MATHIEU 290 ROUTE DE DE SAINT MATHIEU 06130 GRASSE

PCT International Classification Number

A61K 9/48, A61K 8/11

PCT International Application Number

PCT/IB2006/002905

PCT International Filing date

2006-06-21

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	PCT/EP2005/008502	2005-06-21	EPO
2	PCT/EP2005/009226	2005-08-05	EPO