WO2019175331A1 - Extrusion d'agents actifs oxydables - Google Patents

Extrusion d'agents actifs oxydables Download PDF

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Publication number
WO2019175331A1
WO2019175331A1 PCT/EP2019/056455 EP2019056455W WO2019175331A1 WO 2019175331 A1 WO2019175331 A1 WO 2019175331A1 EP 2019056455 W EP2019056455 W EP 2019056455W WO 2019175331 A1 WO2019175331 A1 WO 2019175331A1
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WIPO (PCT)
Prior art keywords
extruder
vitamin
gas
argon
feeding tube
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
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PCT/EP2019/056455
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English (en)
Inventor
Jihane Achkar
Andrea BULBARELLO
Alan CONNOLLY
Stefanie KIRCHEN
Henry Rieger
Kai Urban
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DSM IP Assets BV
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DSM IP Assets BV
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Publication of WO2019175331A1 publication Critical patent/WO2019175331A1/fr
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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/20—Agglomerating; Granulating; Tabletting
    • A23P10/25—Agglomeration or granulation by extrusion or by pressing, e.g. through small holes, through sieves or between surfaces
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A23L33/155—Vitamins A or D
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to the industrial production of extrudates comprising an oxidable active such as vitamin A.
  • Extruding a composition comprising vitamin A is notoriously difficult because vitamin A tends to be degraded during the extrusion process.
  • Vitamin A and derivatives of vitamin A are susceptible to oxidation. Therefore, encapsulation in a protective matrix is required. Whereas vitamin A is poorly soluble in water, the encapsulant should be water-soluble to release vitamin A quickly when brought into contact with an aqueous medium such as porridge, gastric juice or saliva.
  • an aqueous medium such as porridge, gastric juice or saliva.
  • An example of a suitable encapsulant are protective colloids.
  • Cost effectiveness can be achieved by eliminating one step in a multistep process, by running a process in a continuous manner, by avoiding expensive adjuvants and/or by reducing the loss of product during processing.
  • a pulverulent protective colloid can be fed into the first barrel of an extruder before feeding water and other liquids (such as molten vitamin A) in subsequent barrels.
  • Eliminating the pre-mixing step allows the process to be run in a continuous manner as disclosed in WO 2013/127807.
  • the downside of such approach is the loss of vitamin A during the extrusion process. Pulverulent compositions entrap oxygen-containing air. Therefore, when feeding a dry, pulverulent composition into an extruder, the extruder’s screw will move the solids and also oxygen which then comes in contact with the oxidable active (e.g. with oxygen sensitive vitamin A). As a result, significant amounts of the oxidable active are lost during extrusion due to oxidation.
  • the oxidable active e.g. with oxygen sensitive vitamin A
  • Purging the extruder with nitrogen prior to extrusion is of limited value. If the process is run continuously, oxygen-containing air is constantly being added into the extruder resulting in the displacement of nitrogen and creating an oxygen-rich environment within the extruder.
  • Protective gases other than nitrogen are known in the art. Examples are noble gases such as argon. Argon, krypton and xenon, however, are significantly more expensive than nitrogen. Therefore, process engineers systematically avoid noble gases.
  • vent type extruders which enable air to escape from the inner of the extruder, cannot prevent the oxidation of an oxidable active such as vitamin A.
  • the present invention relates to solid extrudates having a particle size from 50 pm to 2000 pm.
  • the extrudates are preferably water-soluble or water-dispersible.
  • the oxidable active may be a water-insoluble oxidable active such as vitamin A.
  • a water-insoluble oxidable active such as vitamin A.
  • one problem to be solved by the present invention is the provision of water- soluble or water-dispersible extrudates comprising at least one water-insoluble oxidable active. Water-solubility or water- dispersibility of a particle can be improved by increasing the surface:volume ratio of the particle. However, such an approach is not promising for particles comprising an oxidable actives. Increasing the
  • water-solubility or water- dispersibility can be improved without negative effect on stability by providing extrudates that comprise gas inclusions, said inclusions comprising or essentially consisting of argon, krypton and/or xenon gas.
  • gas inclusions comprising or essentially consisting of argon, krypton and/or xenon gas.
  • Porous particles dissolve more easily than very dense particles.
  • a further problem to be solved by the present invention is to avoid or minimize the degradation of an oxidable active such as vitamin A during extrusion. This allows for the provision of an extrudate which comprises small amounts of oxidized and/or hydrolyzed vitamin A when measured within 12 hours after extrusion.
  • a further problem to be solved by the present invention is to provide a storage stable extrudate comprising a source of vitamin A.
  • a further objective of the present invention is to provide a cost-effective method for extruding compositions comprising oxidable actives.
  • the problems underlying the present invention are solved by cleansing the extrudate’s matrix of oxygen before allowing it to come into contact with the oxidable active.
  • oxygen-containing pulverulent material is continuously fed into the extruder.
  • cleansing is achieved by displacing the powder’s air with argon, krypton and/or xenon gas.
  • the apparatus according to invention eliminates the need for a constant flow of argon, krypton and/or xenon, even if the extrusion is being run in a continuous manner. Thus, cleansing can be done in a cost-effective manner, despite of the high cost of argon, krypton and xenon gas.
  • the apparatus according to the invention comprises
  • Material feeding tube (4) is partially filled with argon, krypton and/or xenon gas. Because said protective gases are heavier than air, material feeding tube (4) contains - figuratively speaking - an invisible lake consisting of protective gas.
  • pulverulent material is falling into an invisible lake consisting of argon, krypton and/or xenon gas when being fed into extruder (1 ).
  • Said pulverulent material contains air which - similar to air bubbles in a pond - is rising in the lake made of the heavy protective gas. As a result thereof, unwanted
  • oxygen-containing air is displaced by argon, krypton and/or xenon gas, i.e. the pulverulent material is cleansed of oxygen.
  • the apparatus according to the invention allows for a continuous extrusion process in an environment which is substantially free of oxygen. This can be achieved at very low cost because there is no need for a constant flow of protective gas.
  • the apparatus according to the invention prevents or significantly reduces the degradation of oxidable actives during the extrusion process.
  • no extra amount of oxidable active needs to be added for compensating the loss during extrusion.
  • Extrudates manufactured with the apparatus of the invention comprise very small amounts of oxidized and/or hydrolyzed vitamin A when measured within 12 hours after extrusion.
  • the density of a substance is the ratio between its mass and the volume it occupies. If one compares the density of a gas with air, said gas might be heavier than air, lighter than air or neutral with air. This is referred to as“relative density”. At standard conditions (0°C, 1013 hPa), air has a density of 1 .3 kg/m 3 , whereas gases heavier than air have a density of more than 1.3 kg/m 3 (under the same conditions).
  • Heavy gas models help in predicting the concentrations due to release of gases heavier than air.
  • Various dispersion models are known to the person skilled in the art.
  • WO 2004/7064527 discloses a pit having a C0 2 atmosphere for stunning slaughter animals.
  • a container When a container is partially filled with a gas having a density of more than 1.3 kg/m 3 , two phases are formed within the container: the lower part of the container is filled with the gas being heavier than air, whereas the upper part of the container contains air. The two phases are separated by an approximately flat surface, resembling the surface of a pond. Within the container, air is sitting on the surface of the gas being heavier than air, like a lid.
  • the container does not need to be closed and may comprise one or more openings: as long as the opening is above the surface separating the two phases, the gas being heavier than air will remain in the container.
  • the same principle applies to the apparatus according to the invention.
  • the apparatus comprises an extruder with a material feed port which connects the extruder to a material feeding tube.
  • Gas consisting of argon, krypton and/or xenon gas fills the extruder and expands partially into the material feeding tube such that two phases are formed within said material feeding tube: the upper phase consists of air whereas the lower parts of the material feeding tube consists of argon, krypton and/or xenon gas.
  • the two phases are separated by an approximately flat surface, resulting from the gravitational force affecting argon, krypton and/or xenon gas.
  • the apparatus comprises - figuratively speaking - a lake consisting of argon, krypton and/or xenon gas, said lake filing the extruder and expanding into material feeding tube.
  • Argon, krypton and/or xenon are invisible gases.
  • the term“lake” as used in the context of the present invention refers to invisible gas consisting of argon, krypton and/or xenon gas, being filled in the apparatus of the invention and being superimposed by air.
  • the shape and position of the material feeding tube are not particularly restricted as long as a lake consisting of argon, krypton and/or xenon gas and expanding from the extruder into the material feeding tube can be formed.
  • argon is the preferred gas of the present invention.
  • the term“noble gas” means argon gas, krypton gas, xenon gas or mixtures thereof. Said gases are protective gases.
  • Nitrogen is a protective gas but not a noble gas. It is about 3% lighter than air and thus, it cannot be used to implement the present invention.
  • Figure 1 shows a cross section of the apparatus according to the invention. Only the most important parts are shown. Invisible gases are not shown in Figure 1.
  • Extruder (1 ) is shown partially only.
  • the extruder according to the invention has preferably at least one screw and is most preferably a twin-screw extruder. In Figure 1 , screws are not shown.
  • the exit of the extruder e.g. a die
  • the exit of the extruder should be closable. If the extruder’s exit is not closed while argon, krypton and/or xenon gas is being filled into the extruder, said gas will constantly flow out of the extruder. This will increase the amount of noble gas needed which is not desired.
  • noble gas cannot flow out of the extruder, i.e. the extruder’s exit can be opened for extruding strands.
  • Extruder (1 ) has a material feed port (2) which may or may not be an integral part of the extruder.
  • the shape of material feed port (2) is of minor importance as long it allows to connect material feeding tube (4) to extruder (1 ).
  • the connection is air-tight to avoid the loss of noble gas, said noble gas extending from extruder (1 ) to material feeding tube (4).
  • a seal may be used to improve air tightness of the connection between the extruder’s material feed port (2) and said material feeding tube (4).
  • Material feeding tube (4) -shown in black in Figure 2- has at least two openings.
  • the second opening is used to establish a connection to hopper (3) such that pulverulent material can be fed from hopper (3) through material feeding tube (4) into extruder (1 ).
  • the connection between hopper (3) and material feeding tube (4) does not need to be air-tight because the level of the lake consisting of argon, krypton and/or xenon gas is typically below said connection.
  • Material feeding tube (4) may have a third opening (5) which does not cause the draining of the lake consisting of argon, krypton and/or xenon gas even if said opening (5) is left open.
  • said lake does not flow out of opening (5) because the level of said lake is below opening (5).
  • Opening (5) can be used to fill the apparatus according to the invention with argon, krypton and/or xenon gas.
  • a tube being connected to a source of argon, krypton and/or xenon gas is introduced into opening (5).
  • Opening (5) may or may not have a closure.
  • Hopper (3) may have any shape as long it allows to feed pulverulent material into material feeding tube (4).
  • Figure 1 an apparatus is shown wherein pulverulent material flows due to gravitational force from hopper (3) through material feeding tube (4) into extruder (1 ).
  • Hopper (3) and/or material feeding tube (4) may have a different shape than the shape shown in Figure 1. Additional elements such as means for providing a smooth flow of the pulverulent material may be added.
  • Such mean may be a vibrational device being attached to hopper (3).
  • Hopper (3) may be made of one or multiple parts. This also applies to material feeding tube (4) and extruder (1 ).
  • Material feeding tube (4) may be connected to a source of argon, krypton and/or xenon gas. Said connection may be permanent or non-permanent.
  • Figure 2 shows a preferred embodiment of the invention.
  • extruder (1 ) has six barrels (indicated by I to VI). Pulverulent material is filled into extruder (1 ) at the first barrel, whereas water and the oxidable active are introduced into extruder (1 ) in subsequent barrels (not shown in Figure 2).
  • the shape of hopper (3) is not specified in Figure 2; instead, a rectangle is shown as a place holder.
  • Material feeding tube (4) is shown translucent. A tube (shown as thin arrow in
  • Figure 2 being connected to a source (6) of argon, krypton and/or xenon gas has been introduced into opening (5) of material feeding tube (4).
  • the flow of pulverulent material from hopper (3) through material feeding tube (4) into extruder (1 ) is partially indicated with non-filled arrows in Figure 2.
  • Material feed port (2) of extruder (1 ) is not shown in Figure 2. It is to be understood that the apparatus shown in Figure 2 allows pulverulent material to be fed from hopper (3) through material feeding tube (4) into extruder (1 ). It is also to be understood that in Figure 2, material feeding tube (4) is connected to material feed port of extruder (1 ) such that extruder (1 ) can be filled with argon, krypton and/or xenon gas through opening (5).
  • hachures depict those parts of the argon, krypton and/or xenon gas extending into material feeding tube (4). Although hachures are shown in material feeding tube (4) only, it is to be understood that extruder (1 ) is filled with argon, krypton and/or xenon gas, too. At the outset, extruder (1 ) is filled with air. When argon, krypton and/or xenon gas is filled through opening (5) in extruder (1 ) - whose exit/die has preferably been closed - the air in extruder (1 ) is displaced by said heavy noble gas. The displaced air escapes through opening (5).
  • argon, krypton and/or xenon gas is expanding from extruder (1 ) into material feeding tube (4), i.e. an invisible lake consisting argon, krypton and/or xenon gas is established in material feeding tube (4) and extruder (1 ).
  • Pulverulent material is then fed from hopper (3) through material feeding tube (4) into extruder (1 ).
  • the pulverulent material As the solid parts of the pulverulent material are falling into material feeding tube (4) and thus into the lake of noble gas, the pulverulent material’s air is replaced by argon, krypton and/or xenon gas.
  • the pulverulent material contains little or no oxygen. Due to this cleansing process, the level of the invisible lake within the apparatus is descending. However, the level is descending very slowly only and thus, refilling argon, krypton and/or xenon gas through opening (5) might not be necessary for a long time.
  • Preferred extruders have no more than 9 barrels corresponding to a
  • Extruder (1 ) has material feed port (2) and preferably at least two additional inlets.
  • pulverulent material is fed into extruder (1 ) through material feed port (1 ) before water is added through a first inlet.
  • One or more oxidable actives are then added through a second inlet.
  • extruder (1 ) has at least six barrels with a length/diameter ratio from 20 to 30, wherein a first inlet is located on the second or third barrel and wherein the second inlet is located on the fourth or fifth barrel. The most preferred length/diameter ratio is 25.
  • extruder comprises usually one or more screw shafts on which various conveying or kneading type screw elements are mounted.
  • extruder (1 ) is a twin-screw extruder.
  • the present invention also relates to the use of an apparatus for manufacturing extrudates comprising at least one oxidable active, said apparatus comprising - an extruder (1 ) having a material feed port (2), - a hopper (3),
  • said at least one oxidable active is preferably a source of vitamin A such as vitamin A palmitate, and
  • said gas is preferably argon gas.
  • the present invention also relates to a method for extruding a composition comprising at least one oxidable active, wherein a pulverulent material is fed from hopper (3) through material feeding tube (4) into extruder (1 ), characterized in that air contained in said pulverulent material is at least partially replaced by argon, krypton and/or xenon gas before said powder reaches the at least one screw of extruder (1 ).
  • said at least one oxidable active is a source of vitamin A.
  • the most preferred embodiment of the present invention relates to a method for extruding a composition comprising vitamin A palmitate.
  • the pulverulent material - which is being fed from hopper (3) through material feeding tube (4) into extruder (1 ) - is preferably a flowable material.
  • Said material may be a mixture of several compounds.
  • said pulverulent material comprises at least one protective colloid such as a modified starch.
  • “modified starch” refers to a starch ester.
  • Particularly preferred is octenyl succinate starch such as HI-CAP®
  • a preferred embodiment of the present invention relates to a method for extruding a composition
  • a composition comprising a source of vitamin A, wherein a pulverulent material is fed from hopper (3) through material feeding tube (4) into extruder (1 ), characterized in that air contained in said pulverulent material is at least partially replaced by argon gas before said powder reaches the at least one screw of extruder (1 ),
  • said pulverulent material comprises at least one protective colloid such as modified starch, and
  • modified starch is preferably octenyl succinate starch, and wherein said source of vitamin A is preferably vitamin A palmitate.
  • a further preferred embodiment of the present invention relates to a method for extruding a composition comprising at least one oxidable active, said method comprising the steps
  • extruder (1 ) has preferably at least six barrels
  • said first inlet is preferably located on the second or third barrel of extruder (1 ), and
  • extruder (1 ) comprises argon gas, said argon gas expanding partially into material feeding tube (4).
  • extruder (1 ) is preferably neither heated nor cooled, i.e. extrusion preferably takes place under adiabatic conditions.
  • temperature at the extruder’s die raises. After about 30-60 minutes, temperature reaches a certain level and then remains at an approx constant level for the rest of the extrusion.
  • the temperature inside the extruder does not exceed 100 °C. Heating of the oxidable active or of the oxidable actives might be necessary for smooth injection into the extruder, depending on the melting temperature of the oxidable active or of the oxidable actives. If a mixture of several oxidable actives is injected into the extruder, the mixture might require continuous stirring prior to injection into the extruder.
  • the total residence time for the ingredients in the extruder is usually between 60 and 120 s.
  • a die having at least one hole is attached at the exit of the extruder.
  • a die having 10 to 200 holes is used, each hole of having a diameter of preferably 0.5 mm to 1.5 mm.
  • Such dies are commercially available, e.g. at Thermo Fischer, Düsseldorf, Germany.
  • the extruded strand can then be die face cut using e.g. a Thermo electron Kopf-Granulator. Alternatively but not prefered, the strand can be manually cut into extrudates.
  • extrudate refers to solid particles which are preferably water-soluble or water-dispersible.
  • A“water- soluble” or“water-dispersible” extrudate falls apart when put into 2 dl water at a temperature of 30°C under stirring with a spoon at 60 rpm (revolutions per minute) for less than two minutes.
  • water-soluble and“water-dispersible” means that the extrudate falls apart when put into 2 dl water at a temperature of 22°C under stirring with a spoon at 60 rpm (revolutions per minute) for less than two minutes.
  • the extrudate of the invention has preferably a length from 50 pm to 2000 pm, wherein“length” is referring of the longest linear distance that can be measured. This definition of length takes into consideration that the particle might have an irregularly shape such as the shape of a potato. In case of spherical extrudates, the sphere’s diameter corresponds to the length of the particle. Spherical extrudates are obtainable e.g. by spheronization of cylindrical extrudates. In a preferred embodiment of the invention, extrudates fulfil the specification
  • the extrudates may be dried, e.g. on a fluid bed dryer. Typically, a temperature of 40°C to 70 °C is applied for 30 minutes to 120 minutes. Adequate particle flow in the fluid bed dryer is ensured by a constant air flow.
  • the dried extrudates typically contain residual water, e.g. 4-6 weight-% of the total weight of the extrudate, including residual water.
  • weight-% always relate to the total weight of the dried extrudate, not taking into account any residual water.
  • the present invention also relates to extrudates obtainable by the method according to the invention.
  • extrudates may be recognized by smaller or larger inclusions of argon gas.
  • a preferred extrudate according to the invention comprises at least one gas inclusion, said gas inclusion comprising at least 80 vol.-% argon.
  • Figure 3 shows a SEM analysis of typical extrudate. Multiple inclusions
  • the present invention also relates to extrudates comprising vitamin A palmitate but no or very little oxidized and/or hydrolyzed vitamin A palmitate such as retinol, retinaldehyde and/or retinoic acid.
  • a preferred extrudate according to the invention comprises vitamin A palmitate and less than 1 weight-% of oxidized and/or hydrolyzed vitamin A palmitate, wherein said oxidized and/or hydrolyzed vitamin A palmitate is preferably selected from the group consisting of retinol, retinaldehyde and retinoic acid.
  • the recovery of vitamin A palmitate from extrudates according to the invention is exceptionally high.
  • “recovery of vitamin A palmitate” is the vitamin A palmitate content being measured by HPLC within 12 hours after extrusion and being indicated in percentages of the calculated (i.e. theoretical) vitamin A palmitate content.
  • the recovery of vitamin A palmitate from extrudates according to the invention is preferably more than 80%, more preferably more than 90% and most preferably more than 95% of the calculated vitamin A palmitate content.
  • Extrudates according to the invention are also storage stable.
  • “storage stable” refers to the vitamin A palmitate content being measured by HPLC 12 weeks after extrusion. Storage stability is indicated in percentages of the vitamin A palmitate content which has been measured within 12 hours after extrusion by HPLC. The person skilled in the art understands that storage stability is different from recovery. A high recovery of vitamin A palmitate is achieved when the apparatus and/or method according to the invention is used. However, a high recovery does not automatically mean“storage stable” although extrudates having low recovery of vitamin A palmitate typically lack storage stability.
  • the matrix of the invention’s extrudate may consist of one compound only or may comprise more than one compound. Surprisingly, recovery of vitamin A palmitate is particularly good if the extrudate comprises a mixture of octenyl succinate starch and dextrin.
  • the extrudate comprises at least 10 weight-% octenyl succinate starch.
  • Octenyl succinate starch is commercially available e.g. as HiCap®.
  • weight-% always refers to the total weight of the extrudate, not including any residual water.
  • the term“dextrin” refers to a mixture of carbohydrates obtainable by the hydrolysis of starch or glycogen. In the context of the present invention and despite of being a mixture,“dextrin” is treated as a single compound when calculating its amount in weight-% of the total weight of the extrudate.
  • the extrudate comprises at least 10 weight-% dextrin.
  • dextrin Different kinds of dextrin are known and commercially available. A commercially available brand is Crystal Tex®.
  • vitamin A palmitate binds to the OH groups of dextrin which helps prevent crystallization.
  • the weight ratio between octenyl succinate starch and dextrin is from 2:1 to 1 :2. Particularly preferred is a weight ratio from 1.5:1 to 1 :1.5. The most preferred weight ratio is 1 :1.
  • a preferred embodiment of the invention relates to an extrudate which comprises vitamin A palmitate, octenyl succinate starch and dextrin, and wherein the weight ratio between said octenyl succinate starch and said dextrin is from 2:1 to 1 :2, preferably from 1 .5:1 to 1 :1.5 and is most preferably 1 :1.
  • the extrudate of the invention comprises at least 30 weight-% octenyl succinate starch and preferably at least 30 weight-% dextrin, wherein the above-mentioned weight ratios between octenyl succinate starch and dextrin apply.
  • the person skilled in art knows how to apply this teaching. He knows, for example, that all weight percentages must add up to 100 weight-% (not taking into account any residual water, unless indicated otherwise). Thus, he would refrain from choosing weight percentages and/or weight ratios in an unreasonable manner.
  • the extrudate of the present invention may comprise at least one antioxidant. Preferably, antioxidants are present in an amount of at less than 10 weight-% of the total weight of the extrudate (not including any residual water).
  • the extrudate of the invention may comprise fat-soluble antioxidants.
  • the extrudate comprises from 0.01 weight-% to 5 weight-% of one or more fat-soluble antioxidants, based on the total weight of the extrudate (not including any residual water).
  • extrudates comprising comprises from 0.05 weight-% to 3 weight-% of one or more fat-soluble antioxidants, the total weight of the extrudate (not including any residual water).
  • Preferred fat-soluble antioxidants are a-tocopherol, b-tocopherol, y-tocopherol and d-tocopherol. Particularly preferred is a mixture comprising a-tocopherol, b-tocopherol, g-tocopherol and d-tocopherol. Such a mixture is referred to as “mixed tocopherols” and is commercially available at DSM® Nutritional Products under the brand“Mixed Tocopherols 95”.
  • “Mixed tocopherols 95” as available at DSM® Nutritional Products comprises a- tocopherol, b-tocopherol, g-tocopherol and d-tocopherol. Said tocopherols are typically (R,R,R)- tocopherols. In contrast, all-rac tocopherol is noted as dl- tocopherol.
  • the total tocopherol content of“mixed tocopherols 95” is at least 95 weight-%, based on the total weight of the product (not including any residual water). It comprises more d-tocopherol than a-tocopherol, i.e. the weight ratio a-tocopherol: d-tocopherol in“mixed tocopherols 95” is less than 1. It also comprises more y- tocopherol than a-tocopherol, i.e. the weight ratio a-tocopherol: g-tocopherol in “mixed tocopherols 95” is less than 1.
  • the weight ratio a-tocopherol: non-a- tocopherol in“mixed tocopherols 95” is less than 1 , wherein the term“non-a- tocopherol” is referring to the accumulated weight of b-tocopherol, y-tocopherol and d-tocopherol.
  • the extrudate of the invention is particularly stable if a mixture comprising a-tocopherol b-tocopherol, y-tocopherol and/or d-tocopherol is added.
  • the weight ratio between a-tocopherol and d-tocopherol ratio is from 0.5:1 to 2:1 , more preferably from 0.5:1 to 1 : 1 and most preferably from 0.5:1 to 0.9:1.
  • the weight ratio between a-tocopherol and y-tocopherol ratio is from 0.5:1 to 2:1 , more preferably from 0.5:1 to 1 :1 and most preferably from 0.5:1 to 0.9:1.
  • the present invention also relates to the use a mixture comprising a-tocopherol, b-tocopherol, g-tocopherol and d-tocopherol for manufacturing an extrudate comprising a source of vitamin A such as vitamin A palmitate.
  • Extrudates comprising vitamin A palmitate were manufactured with an apparatus as shown in Figure 2.
  • Said apparatus comprises extruder (1 ) and material feeding tube (4), wherein material feeding tube (4) is attached to the extruder’s material feed port (not shown in Figure 2). If necessary, a sealing ring may be introduced between material feeding tube (4) and the extruder’s material feed port for providing an air-tight connection.
  • argon gas was filed into extruder (1 ) through opening (5) of material feeding tube (4).
  • the extruder’s exit/die was closed such that material feeding tube (4) and extruder (2) could be filled with argon.
  • Opening (5) could be left open because argon gas is heavier than air.
  • a lake consisting of argon was thus formed, said lake extending from extruder (1 ) to material feeding tube (4).
  • hachures depict those parts of the invisible argon lake which extend into material feeding tube (4). Once the argon lake had been established, no further supply of argon gas was needed.
  • a dry pulverulent mixture of modified food starch (HiCap®100) and dextrin (Crystal Tex® 644) was then fed from hopper (3) through material feeding tube (4) into extruder (1 ).
  • air comprised in said pulverulent mixture was being displaced by argon gas.
  • the amount of argon gas in material feeding tube (4) kept decreasing. Said decrease was slow such that material feeding tube (4) comprised at any time at least approx. 50 vol.-% of argon.
  • demineralized water was injected into barrel 2 of the extruder.
  • Molten oxidable actives comprising vitamin A palmitate (from DSM® Nutritional Products) and other fat-soluble actives were then injected into the extruder barrel at position 4.
  • Emulsification took place within extruder (1 ).
  • Adiabatic temperature was approx. 80°C after 60 minutes of continuous extrusion.
  • Table 1 calculated composition of dried extrudates, based on the total dry weight
  • Example 1 was repeated with the same calculated composition (cf. table 1 ) and the same apparatus. However, in contrast to Example 1 , no argon gas was filled into the apparatus before starting the extrusion.
  • Example 3
  • Example 1 the amount of vitamin A palmitate in the extrudates of Example 1 and Example 2 were measured by HPLC (high- performance liquid chromatography) using a C18 column (Thermo Scientific ODS Hypersil) and a variable wavelength Diode-Array Detector (DAD, Hewlett Packard Agilent Series 1 100). The measured vitamin A palmitate content was then compared with the calculated vitamin A palmitate content. Results are given in Table 2.
  • Example 3 clearly shows that the amount of vitamin A palmitate which is degraded and thus lost during extrusion can be significantly reduced when the apparatus according to the invention is used.
  • Example 4 the effect of the invention is measured using the oxidation marker 5,6-epoxy-retinyl palmitate which has previously been identified as one of the major breakdown products of Vitamin A palmitate. It occurs directly as a result of contact between vitamin A palmitate and oxygen. This oxidation marker has been measured by RP-HPLC, as previously described.
  • Example 4 clearly shows that a much lower amount of vitamin A palmitate is oxidized during extrusion if the extrusion is done according to the invention.
  • Maltodextrin DE 0508 is commercially available Glucidex 6 (Roquette).
  • a molten mixture of the respective vitamin A ester (palmitate or acetate), dl-a- tocopheryl acetate (as a source of vitamin E), vitamin D3 and dl-a-tocopherol (as fat-soluble antioxidant) was fed at 80°C into barrel 4, said barrel 4 being located downstream of barrels 1 and 2. Thermal heating had been applied to oil feed lines to ensure that temperature is maintained.
  • extrudates were then dried on a fluid bed dryer.
  • the dried extrudates typically contained of 4-6 weight-% residual water.
  • the extrudates were then sieved to retain and store extrudates having a particle size from 212 pm to 1000 pm.
  • Table 4 matrices used in Example 5; the respective extrudates were identical apart from the source of vitamin A (palmitate vs. acetate)
  • Table 5 stability of vitamin A: content of vitamin A palmitate and vitamin A
  • Table 6 stability of vitamin A: content of vitamin A palmitate and vitamin A acetate, respectively, being measured 12 weeks after extrusion and being indicated in percentages of the vitamin A palmitate/acetate content which has been measured within 12 hours after extrusion by HPLC. Extrudates were stored in sealed aluminum pouches at 30°C and 65% relative humidity.
  • Example 5 clearly shows that extrudates comprising vitamin A palmitate are more stable than extrudates comprising vitamin A acetate. Example 5 also shows that different kinds of dextrin can be used.
  • Example 6 shows that the addition of a fat-soluble antioxidant is beneficial, in particular when tocopherol is added. Very good results are achieved when “non-a-tocopherol” is added in addition to a-tocopherol.
  • Dry pulverulent matrix material was fed into barrel 1 using a Brabender
  • Barrel 4 was separated from barrel 2 by one barrel (i.e. separated by barrel 3).
  • the extruder was neither heated nor cooled, i.e. extrusion took place under adiabatic conditions. After about 60 minutes of continuous extrusion, the temperature at the die remained stable at approximately 80°C. Once the temperature at the die reached 80°C, die face cutting began.
  • the extrudates were then dried on a fluid bed dryer. The dried extrudates typically contained residual water of 4-6 weight-% of the total weight of the extrudate. The extrudates were then sieved and extrudates having a particle size from 212 pm to 1000 pm were retained and stored.
  • Table 8 calculated composition of dried extrudates, based on the total dry weight
  • the matrix of the extrudate consists of octenyl succinate starch and dextrin. Vitamin E acetate is not part of the matrix because it is an active (cf. definition of“matrix” as used in the context of the present invention).
  • the extrudates were then sieved to retain and store extrudates having a particle size from 212 pm to 1000 pm.

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Abstract

La présente invention concerne la production industrielle de particules comprenant au moins un agent actif oxydable. L'appareil de l'invention comprend une extrudeuse qui est reliée à une source d'argon, de krypton et/ou de xénon gazeux. Ledit appareil peut être utilisé pour fabriquer des extrudats hydrodispersibles qui comprennent des agents actifs oxydables insolubles dans l'eau tels que le palmitate de vitamine A.
PCT/EP2019/056455 2018-03-15 2019-03-14 Extrusion d'agents actifs oxydables Ceased WO2019175331A1 (fr)

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000021504A1 (fr) * 1998-10-09 2000-04-20 General Mills, Inc. Particules discretes de longue conservation obtenues par encapsulation de composants liquides sensibles dans une matrice
US20020110599A1 (en) * 2000-11-29 2002-08-15 Helmut Auweter Production of solid preparations of water-soluble, sparingly water-soluble or water-insoluble active compounds
WO2004064527A1 (fr) 2003-01-17 2004-08-05 Butina Aps Procede et dispositif pour etourdir des animaux de boucherie
US20040199492A1 (en) * 2003-04-04 2004-10-07 Maniak Douglas C Method of manufacturing dough products via gas injection and accelerational mixing
US20100284987A1 (en) * 2007-07-19 2010-11-11 Dsm Ip Assets B.V. Tablettable formulations of lipophilic health ingredients
US20120071563A1 (en) * 2010-08-05 2012-03-22 Basf Se Stabilizer
AU2011287566A1 (en) * 2010-08-05 2013-02-28 Basf Se Stabilizer
WO2013127807A1 (fr) 2012-02-28 2013-09-06 Dsm Ip Assets B.V. Procédé d'extrusion
US20170258725A1 (en) * 2014-08-11 2017-09-14 Perora Gmbh Formulation comprising particles

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000021504A1 (fr) * 1998-10-09 2000-04-20 General Mills, Inc. Particules discretes de longue conservation obtenues par encapsulation de composants liquides sensibles dans une matrice
US20020110599A1 (en) * 2000-11-29 2002-08-15 Helmut Auweter Production of solid preparations of water-soluble, sparingly water-soluble or water-insoluble active compounds
WO2004064527A1 (fr) 2003-01-17 2004-08-05 Butina Aps Procede et dispositif pour etourdir des animaux de boucherie
US20040199492A1 (en) * 2003-04-04 2004-10-07 Maniak Douglas C Method of manufacturing dough products via gas injection and accelerational mixing
US20100284987A1 (en) * 2007-07-19 2010-11-11 Dsm Ip Assets B.V. Tablettable formulations of lipophilic health ingredients
US20120071563A1 (en) * 2010-08-05 2012-03-22 Basf Se Stabilizer
AU2011287566A1 (en) * 2010-08-05 2013-02-28 Basf Se Stabilizer
WO2013127807A1 (fr) 2012-02-28 2013-09-06 Dsm Ip Assets B.V. Procédé d'extrusion
US20150056345A1 (en) * 2012-02-28 2015-02-26 Dsm Ip Assets B.V. Extrusion process
US20170258725A1 (en) * 2014-08-11 2017-09-14 Perora Gmbh Formulation comprising particles

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