Granules containing encapsulated active ingredients

Abstract

The present invention relates to water-soluble or water-dispersible granules obtained by continuous melt granulation. In one embodiment, the granules comprise at least one binder, at least one filler, and microcapsules encapsulating a fat-soluble active ingredient.

Description

Detailed Description of the Invention

[0001] [Technical field] The present invention relates to edible water-dispersible powders.

[0002] [Background of the invention] Fat-soluble active ingredients cannot be dissolved in water because of their fat solubility. Therefore, it is common to encapsulate fat-soluble active ingredients. Water-dispersible microcapsules containing fat-soluble micronutrients (e.g., fat-soluble vitamins) are commercially available from DSM Nutritional Products (Switzerland).

[0003] Microcapsules often have poor flowability, mainly due to their small particle size.To obtain a flowable powder, the microcapsules are granulated.

[0004] Granulation is a size-enlarging process that is often performed by wet granulation, which uses a solvent (water or organic solvent) to initiate bonds between solid particles (e.g., microcapsules). Dry granulation and melt granulation are known alternatives to wet granulation. Melt granulation operates on a similar principle to wet granulation, but typically uses a molten binder as the granulation fluid to establish liquid bridges between the particles to be granulated. Upon cooling to room temperature, the binder solidifies and forms bridges between the individual powder particles, resulting in a solid final product with a granular structure.

[0005] In most cases, melt granulation is carried out in a heated powder bed. It is a batch process: the processing of the next batch has to wait until the current one is finished. This also applies to wet granulation, which is carried out in conventional high shear mixers.

[0006] The disadvantage of wet granulation is the need to remove the solvent at the end of the granulation process. In the case of using water as the solvent, a significant amount of energy is required to distill off the water. A further disadvantage of wet granulation is the risk of hydrolysis of the active ingredient. In the case of organic solvents, potentially harmful residues and / or adverse effects on the environment are of concern.

[0007] During granulation, the microcapsules and their contents should be largely intact. The resulting granules should be flowable, storage stable and / or water dispersible. The amount of fines (i.e., non-granulated residue) and / or the amount of surface oil should be low.

[0008] A need exists for a process for granulating microcapsules in a cost-effective, efficient, and environmentally friendly manner.

[0009] [Summary of the invention] The problem underlying the present invention is solved by continuous melt granulation of a mixture containing microcapsules. The continuous melt granulation process is preferably carried out in an extruder. In a preferred embodiment of the present invention, a co-rotating twin screw extruder continuously churns out free-flowing granules: no die is required at the end of the extruder.

[0010] In addition to the microcapsules, the mixture of the present invention includes at least one edible binder. During the continuous melt granulation, the binder of the mixture is melted or at least softened.

[0011] In one embodiment, the microcapsules to be granulated contain a fat-soluble active ingredient. Some fat-soluble active ingredients are temperature sensitive. When carrying out the continuous melt granulation process of the present invention, it is desirable to avoid extremely high temperatures. Therefore, binders with very high melting temperatures or very high glass transition (Tg) temperatures are not preferred. In this specification, "very high" can mean higher than 200°C or higher than 250°C.

[0012] In one embodiment, the mixture of the present invention further comprises at least one edible filler.In contrast to hot melt extrusion, during the continuous melt granulation process of the present invention, it is not necessary to melt at least one edible filler.Therefore, the melting temperature of at least one edible filler can be significantly higher than the melting temperature of at least one binder.

[0013] A preferred mixture includes a filler, a binder and a microcapsule, The mixture comprises 0.1% to 55% by weight of microcapsules based on the total weight of the mixture; and The mixture comprises 5% to 15% by weight of a binder, based on the total weight of the mixture; and The weight ratio of filler to binder is from 4:1 to 9:1; and The melting temperature of the binder is lower than the melting temperature of the filler, and The melting temperature of the filler is 151°C to 240°C.

[0014] In one embodiment, the method for producing granules by continuous melt granulation comprises feeding the mixture into an extruder, preferably a twin screw extruder. In one embodiment, the granules of the present invention comprise the mixture of the present invention. In one embodiment, the granules of the present invention consist of the mixture of the present invention.

[0015] [Detailed Description of the Invention] Continuous granulation is often carried out using an extruder. Extrusion granulation can be carried out using a solvent ("continuous wet granulation") or with heat ("continuous melt granulation").

[0016] The granules of the present invention can be obtained by continuous melt granulation of a dry edible mixture comprising primary particles and at least two edible excipients. During continuous melt granulation, the primary particles are agglomerated. Thus, the granules of the present invention are preferably units formed of a large number of particles. The primary particles of the granules are smaller than the granules.

[0017] Both edible excipients are preferably water-soluble or water-dispersible. The melting temperature of the first edible excipient is low enough to melt or at least soften during continuous melt granulation. When melted or softened, the first edible excipient establishes crosslinks between primary particles. The crosslinks then solidify at room temperature. Thus, the first edible excipient acts mainly as a binder. In the most preferred embodiment of the present invention, the first edible excipient is sorbitol.

[0018] The melting temperature of the second edible excipient is relatively high, so that the edible excipient usually does not melt completely or does not melt at all during continuous melt granulation. The second edible excipient mainly acts as a filler. In the most preferred embodiment, the second edible excipient is inulin.

[0019] The granules of the present invention may contain only one type of primary particle or preferably contain several types of primary particles.The primary particles of the granules of the present invention are preferably water-soluble or water-dispersible and preferably contain at least one active ingredient.In the case of a lipophilic active ingredient, the primary particles are preferably water-soluble or water-dispersible microcapsules that encapsulate the lipophilic active ingredient.Such microcapsules can be obtained by spray drying an emulsion that contains a lipophilic active ingredient and at least one emulsifier.

[0020] The granules of the present invention are preferably water-soluble or water-dispersible. A composition comprising or consisting of such granules is suitable for preparing a beverage.

[0021] [Filler of the present invention] Fillers are excipients used to increase the volume of the granules of the present invention. However, fillers can have additional functions. Some fillers (e.g., dietary fiber) also have health benefits.

[0022] The granules of the present invention are intended for edible use, therefore toxic and non-edible fillers are generally excluded.

[0023] The granules of the present invention are preferably water-soluble or water-dispersible. Thus, fillers having a solubility of less than 1 g / 100 mL water, or less than 0.5 g / 100 mL water, or less than 0.1 g / 100 mL water are not preferred.

[0024] Usually, the melting temperature of the filler is higher than the melting temperature of the binder. It is not necessary to melt or soften the filler during continuous melt granulation. The melting temperature of the filler is preferably at least 150°C, more preferably at least 155°C, and most preferably at least 160°C. The melting temperature of the filler is preferably 151°C to 240°C, more preferably 180°C to 240°C, and most preferably 180°C to 200°C.

[0025] Preferred fillers are inulin, human milk oligosaccharides (HMO) and mannitol. 2'-Fucosyllactose (2'-FL) is the preferred HMO. A preferred filler is a mixture containing 2'-Fucosyllactose (2'-FL) and difucosyllactose (DFL). Granulated standard inulin is the preferred inulin. Standard inulin has an average degree of polymerization (DP) of 10 to 20. Non-preferred fillers are microcrystalline cellulose and pregelatinized starch.

[0026] [Binder of the present invention] Binders are excipients used to hold the components of the formulation together (i.e., solid at room temperature). To do so, the binder is melted or softened during continuous melt granulation. Usually, the binder has a melting temperature lower than that of the filler and often lower than that of any added active ingredient. The binder preferably has a melting temperature lower than 140°C, more preferably lower than 130°C, even more preferably lower than 120°C, and most preferably lower than 110°C. The binder preferably has a melting temperature between 50°C and 110°C, more preferably between 60°C and 100°C, and most preferably between 70°C and 100°C.

[0027] The granules of the present invention are preferably water-soluble or water-dispersible. Thus, binders with a solubility of less than 1 g per 100 mL of water, or less than 0.5 g per 100 mL of water, or less than 0.1 g per 100 mL of water are not preferred. Possible binders are, inter alia, ribose (such as D-ribose), polyethylene glycol, sorbitol and xylitol. The binder of the present invention is preferably a polyol, more preferably a sugar alcohol, even more preferably sorbitol or ribose (e.g. D-ribose), and most preferably sorbitol with a melting temperature of 98°C or less. Such sorbitol is commercially available under the trademark Roquette®.

[0028] [Microcapsules of the present invention] Microencapsulation is a protection technique for encapsulating solid or liquid active ingredients into microparticles having a diameter of, for example, 1 to 900 μm. The granules of the present invention comprise a plurality of microcapsules. The size of the granules therefore varies, inter alia, depending on the size of the microcapsules: larger microcapsules result in larger granules.

[0029] One advantage of microencapsulation is that a solid or liquid active ingredient can be completely or nearly coated and isolated from the external environment. Microencapsulation can make a fat-soluble active ingredient water-dispersible or water-soluble.

[0030] Spray drying is a suitable method for the microencapsulation of fat-soluble active ingredients. Prior to spray drying, the fat-soluble active ingredient is mixed with at least one encapsulating agent, which usually provides an emulsion. Gum arabic is a commonly used encapsulating agent. Spray drying is one of the most widely used microencapsulation techniques, as it quickly evaporates water and maintains a low temperature inside the particles. Spray-dried microcapsules containing fat-soluble vitamins are commercially available from DSM Nutritional Products, Switzerland. Vitamins A, D, E, and K are exemplary fat-soluble vitamins. This includes their derivatives, such as esters.

[0031] Encapsulating a mixture of fat-soluble vitamins is quite unusual. Typically, the fat-soluble vitamins are encapsulated separately. To provide a mixture of fat-soluble vitamins, different types of microcapsules are mixed together.

[0032] [Mixture of the present invention] The mixture of the present invention is suitable for continuous melt granulation. The mixture of the present invention is a powder mixture that can be fed into equipment suitable for continuous melt granulation (e.g., an extruder).

[0033] In contrast to wet granulation, no solvent is required when carrying out continuous melt granulation.Therefore, the mixture of the present invention contains less than 10% by weight, preferably less than 8% by weight, more preferably less than 5% by weight, and most preferably less than 3% by weight of solvent based on the total weight of the mixture.This is particularly true, but not exclusively, when the solvent is water.Therefore, the preferred mixture of the present invention contains less than 10% by weight, preferably less than 8% by weight, more preferably less than 5% by weight, and most preferably less than 3% by weight of water based on the total weight of the mixture.

[0034] The mixture of the present invention comprises or consists of a filler, a binder and a microcapsule.

[0035] Fillers are necessary to increase the size: they increase the volume of the filler, granules of the present invention. The mixture of the present invention preferably comprises 40% to 95% by weight, more preferably 60% to 90% by weight, and most preferably 70% to 80% by weight of at least one filler, based on the total weight of the mixture. The mixture of the present invention comprises a plurality of fillers. However, preferably, the present invention may comprise only one filler. Thereby, the filler is preferably a polysaccharide, more preferably a dietary fiber, even more preferably inulin, and most preferably a granulated inulin powder.

[0036] Usually, the mixture of the present invention contains less binder than filler. The weight ratio of filler to binder is preferably 4:1 to 10:1, more preferably 5:1 to 10:1, even more preferably 6:1 to 9:1, and most preferably 7:1 to 8:1. The mixture of the present invention contains preferably 5% to 15% by weight, more preferably 6% to 14% by weight, and most preferably 8% to 13% by weight of at least one binder, based on the total weight of the mixture. The mixture of the present invention may contain more than one binder. However, it is preferred that the mixture of the present invention contains only one binder. Thereby, the binder is preferably a polyol, more preferably a sugar alcohol, even more preferably sorbitol or ribose, and most preferably sorbitol. The preferred ribose is D-ribose.

[0037] The mixture of the present invention comprises microcapsules. When granulating the mixture of the present invention, there is a certain risk that some microcapsules may be damaged. This risk can be reduced by creating a low shear environment in the extruder (e.g., by selecting suitable kneading elements). However, this risk can also be reduced by reducing the concentration of microcapsules in the mixture of the present invention. The mixture of the present invention preferably comprises 0.1% to 55% by weight, more preferably 1% to 40% by weight, even more preferably 1% to 30% by weight, and most preferably 5% to 20% by weight of microcapsules, based on the total weight of the mixture.

[0038] In one embodiment, the microcapsules described herein encapsulate at least one fat-soluble active ingredient. Preferred fat-soluble active ingredients are fat-soluble micronutrients, such as fat-soluble vitamins and pro-vitamins. Beta-carotene is an example of a fat-soluble pro-vitamin. In one embodiment, the mixture of the present invention comprises only one type of microcapsule. However, in a preferred embodiment, the mixture of the present invention comprises various types of microcapsules. In the case of various types of microcapsules, the mixture of the present invention preferably comprises at least two, more preferably at least three, even more preferably at least four and most preferably at least five fat-soluble active ingredients. In one embodiment, the mixture of the present invention comprises microcapsules comprising vitamin A, microcapsules comprising vitamin E, microcapsules comprising beta-carotene, microcapsules comprising vitamin D, and / or microcapsules comprising vitamin K. In a preferred embodiment, the mixture of the invention comprises microcapsules comprising an ester of vitamin A (such as vitamin A acetate), microcapsules comprising an ester of vitamin E (such as vitamin E acetate), microcapsules comprising beta-carotene, microcapsules comprising vitamin D3, and / or microcapsules comprising vitamin K1.

[0039] [Granules of the present invention] Preferred granules can be obtained by continuous melt granulation (i.e. without solvent) of the mixture according to the invention, preferably using a twin-screw extruder. Thus, the granules according to the invention comprise or consist of the mixture according to the invention.

[0040] The mixture of the present invention comprises primary particles which are preferably microcapsules. During continuous melt granulation, bridges are formed between the primary particles of the mixture. Thus, the granules of the present invention are larger than the size of the primary particles. Preferred granules of the present invention have a mass median particle size D50 (volume based) of 0.5 mm to 6 mm, preferably 1 mm to 5 mm, more preferably 1.5 mm to 4.5 mm, and most preferably 2 mm to 4 mm, measured using dynamic image analysis. The granules of the present invention may comprise more than 10, more than 100, more than 500, or even more than 1000 microcapsules. Each granule may comprise only one type of microcapsule. However, in one embodiment, the granules of the present invention comprise various types of microcapsules. In the case of various types of microcapsules, the granules of the present invention preferably comprise at least two, more preferably at least three, even more preferably at least four, and most preferably at least five lipophilic active ingredients. In one embodiment, the granules of the invention comprise microcapsules containing vitamin A, microcapsules containing vitamin E, microcapsules containing beta-carotene, microcapsules containing vitamin D, and / or microcapsules containing vitamin K. In a preferred embodiment, the granules of the invention comprise microcapsules containing an ester of vitamin A (such as vitamin A acetate), microcapsules containing an ester of vitamin E (such as vitamin E acetate), microcapsules containing beta-carotene, microcapsules containing vitamin D3, and / or microcapsules containing vitamin K1.

[0041] In one embodiment, the granules of the present invention comprise a filler, a binder and microcapsules, The granules contain 0.1% to 55% by weight of microcapsules based on the total weight of the granules; and The granules comprise 5% to 15% by weight of a binder, based on the total weight of the granules; and The weight ratio of filler to binder is from 4:1 to 10:1; and The melting temperature of the binder is lower than the melting temperature of the filler, and The melting temperature of the filler is 151°C to 240°C.

[0042] The granules of the present invention are preferably water-soluble or water-dispersible. This can be achieved by selecting a binder that is water-soluble or water-dispersible, by selecting a filler that is water-soluble or water-dispersible, and by selecting water-soluble and / or water-dispersible microcapsules.

[0043] [Method of Invention] The method of the present invention is continuous melt granulation, preferably continuous twin-screw melt granulation. The differences between batch melt granulation and continuous twin-screw melt granulation are listed in Table 1 of N. Kittikunakorn et al., "Twin-screw melt granulation: Current progress and challenges," International Journal of Pharmaceutics, 588, (2020), 119670. In a preferred embodiment of the present invention, the dry, powder mixture disclosed herein is fed into an extruder that is suitable for continuous melt granulation. Thereby, volumetric powder feeders are not preferred. In a preferred method of the present invention, the mixture of the present invention is fed into an extruder described herein using a gravimetric powder feeder. The gravimetric powder feeder obtains a controlled and consistent feeding process while taking into account changes in powder properties over time and process deviations.

[0044] In the process of the invention, a twin screw extruder is preferably used. Twin screw extruders with co-rotating screws are particularly preferred. The co-rotating screws of the preferred extruders are modular and can be configured in different setups, resulting in different zones. The purpose of the first zone near the inlet of the extruder is transport. The transport zone is often called the conveying zone. It is also possible that there is one or more kneading zones. The kneading zone is usually located between two conveying zones, and there is preferably a shaping zone at the outlet of the extruder.

[0045] In most cases, each zone has different screw elements. The conveying zone has conveying elements that transport the material towards the exit of the granulator [see section 2.1 in N. Kittikunakorn et al., "Twin-screw melt granulation: current progress and challenges," International Journal of Pharmaceutics, 588, (2020), 119670]. The kneading zone has kneading elements with narrow or wide kneading disks. A typical forming zone has at least one size control element that minimizes the amount of oversized granules. An exemplary size control element is shown in Figure 1(f) of J. Vercruysse et al., "Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation," International Journal of Pharmaceutics 479 (2015) 171-180. These size control elements are not knives used to cut the extruded strands. In fact, when performing continuous melt granulation, spaghetti-like strands are not extruded. Extruders suitable for continuous melt granulation do not have a die at the exit [see Figure 1 in N. Kittikunakorn et al., "Twin-screw Melt Granulation: Current Progress and Challenges," International Journal of Pharmaceutics, 588, (2020), 119670]. The size control element is the screw element in the extruder.

[0046] Hot melt extrusion is different from continuous melt granulation as described herein. When performing hot melt extrusion, a strand having, for example, a cylindrical diameter is extruded through a die. The length of the strand is not limited (i.e. it can be unlimited). To obtain separated units, the strand obtained by hot melt extrusion must be chopped into pieces. The pellets obtained are not granules consisting of distinguishable primary particles. When performing hot melt extrusion, the chopping step can be performed at any time after extrusion, including directly at the extruder die. Dies with integrated knives are commercially available.

[0047] The above does not apply to the method of the present invention. When performing continuous melt granulation, strands are not extruded. Instead, granules are continuously mass-produced at the end of the extruder. Since no strands are produced, the knife / cutting step is not necessary, greatly simplifying the process. When performing continuous melt granulation, a die at the end of the extruder is not required. In a preferred embodiment of the present invention, the mixture of the present invention is fed into a twin-screw extruder that does not have a die and does not have a knife cutting device.

[0048] In the process of the invention, the screw configuration of the twin-screw extruder is usually selected so that the extruder has at least one kneading zone. Thus, the at least one kneading zone is preferably closer to the powder inlet of the extruder than the end of the extruder. The kneading zone comprises kneading elements. The kneading elements are preferably kneading disks as disclosed in US 2005 / 0041521. The kneading disks may be coincident or non-coincident and are preferably arranged at a stagger angle of 30° to 90°. A stagger angle of about 30° is preferred, as this limits the stress on the powder mixture. In the context of the present invention, "stagger angle" refers to the angle of vertex offset of two directly successive kneading disks, as explained in paragraph

[0007] of US 2005 / 0041521. By way of example, the expression "kneading disks are arranged at a stagger angle of 30°" means that the vertex offset angle of the successive kneading disks is 30°. There may be more than two consecutive kneading discs in the kneading zone of the extruder. Figure 2 of US 2005 / 0041521 shows a side view of a kneading zone with five consecutive kneading discs, the kneading discs being arranged at a staggered angle.

[0049] Temperature control is important when performing continuous melt granulation. In a preferred method of the present invention, the extruder has several zones that can be heated or cooled individually. When continuously melt granulating the mixture disclosed herein, the temperature zone close to the powder inlet of the extruder is usually heated. When selecting a suitable temperature, it is necessary to consider that the material in the extruder moves quite fast so that the contact between the material and the heating element is quite short. In some cases, therefore, it may be recommended to set the temperature of some zones of the extruder at a temperature higher than the melting temperature of the binder of the mixture.

[0050] In a preferred embodiment of the invention, the conveying zone and / or the kneading zone of the extruder are preferably heated to a temperature of from 90°C to 200°C, more preferably to a temperature of from 100°C to 180°C, and most preferably to a temperature of from 110°C to 170°C.

[0051] It is not preferable to stir hot granules. Hot granules may still be relatively soft and sticky. As a result, hot granules may form lumps. This should be avoided. Therefore, it is preferable to cool the material in the extruder before it is mass-produced by the extruder. In a preferred embodiment of the present invention, at least one zone is cooled after kneading to a temperature of less than 60°C, preferably less than 40°C, and most preferably less than 26°C.

[0052] [Example] [Example 1 (vitamin premix)] In Example 1, a powdered premix was provided that contained a mixture of microcapsules. Each type of microcapsule contained a fat-soluble vitamin or a precursor of a fat-soluble vitamin. All microcapsules were obtained from DSM Nutritional Products (Switzerland).

[0053] The premix provided in Example 1 contained Vitamin A acetate, beta carotene, Vitamin D3, Vitamin E acetate and Vitamin K.

[0054] Example 2 (Ribose as a binder) In Example 2, a dry mix was provided that contained, based on the total weight of the dry mix, 47.13% by weight of inulin Orafti® GR (filler), 10% by weight of D-ribose (binder) and 42.87% by weight of the premix of Example 1. The weight ratio of filler to binder was therefore 4.7:1.

[0055] Preliminary experiments have shown that the lowest possible processing temperature for D-ribose that still produces granules with desirable quality characteristics is about 80°C.

[0056] Orafti® GR is a granulated inulin powder (average degree of polymerization ≧10) available from Beneo, Mannheim, Germany. Its melting point is measured in the range of 190-195° C.

[0057] The dry blend of Example 2 was then fed into a ThermoFisher® Eurolab® extruder using a gravimetric loss-in-weight feeder at the powder inlet. The extruder had a length to diameter (L / D) ratio of 25 / 1 and a screw diameter of 16 mm. The co-rotating screws of the extruder were fully modular and could be configured in various setups. The extruder was divided into several zones that could be heated or cooled separately.

[0058] In Example 2, five extrusion runs were carried out using various temperature schemes. The temperature zones close to the powder inlet (zones 2, 3, and 4) were heated to temperatures between 104° C. and 130° C. The temperature of the zones close to the end of the extruder (zones 5 and 6) was kept at 25° C. Cooling the end of the extruder allowed the material to solidify and prevented sticking of the granules coming out of the extruder.

[0059] In Example 2, the extruder had one kneading zone with three wide kneading disks arranged at a staggered angle of 60° (i.e., the angle of apex misalignment between any two immediately successive kneading disks was 60°).

[0060] All five extrusion runs yielded acceptable granules, however, regardless of the temperature scheme applied, the resulting granules exuded oil, indicating that some microcapsules were damaged during the extrusion process.

[0061] Example 3 (sorbitol as binder) In Example 3, the process of Example 2 was repeated, except that instead of D-ribose, sorbitol was used as the binder. Preliminary experiments showed that the lowest possible processing temperature for sorbitol that still produced granules with desirable quality characteristics was about 85° C. (i.e., slightly higher than for D-ribose).

[0062] In Example 3, five extrusion runs were performed. The same temperature scheme and screw configuration as in Example 2 were applied.

[0063] In all five experiments, reasonable granules were obtained, with less oil oozing out of the granules, indicating that sorbitol performed better than ribose.

[0064] Next, various grades of sorbitol were investigated to further reduce the energy required to produce good water-soluble granules. Samples were analyzed by Differential Scanning Calorimetry (DSC) to determine the grade of sorbitol with the lowest melting energy. When sorbitol grade Xtab300S (available from Roquette®) is used as the binder, the energy required to produce good water-soluble granules is lower than the other grades (see table below).

[0065] [Table 1]

[0066] Example 4 (More Filler: Effect of Dilution) In Example 4, the process of Example 3 was repeated, but with less premix and more filler. The dry mix of Example 4 contained 72.85% by weight of inulin Orafti® GR (filler), 10% by weight of sorbitol (binder) and 17.15% by weight of the premix of Example 1, based on the total weight of the dry mix. The weight ratio of filler to binder was therefore about 7.3:1.

[0067] In Example 4, five extrusion runs were carried out. The temperature scheme of Example 2 was applied. A screw configuration consisting of a single kneading zone with three kneading discs arranged at a stagger angle of 30° was used.

[0068] All five runs yielded good quality granules. No oil was visually exuded from the granules. Example 4 shows the advantage of diluting the microcapsules with a filler: lowering the concentration of microcapsules in the mixture fed into the extruder reduced the stress on the microcapsules. Example 4 also shows the advantage of using a stagger angle of less than 60°.

[0069] [Example 5 (alternative filler)] In Example 5, alternative fillers were tested. To see which fillers were suitable for continuous melt extrusion, some were processed as placebo blends (90% filler, 10% sorbitol as binder). The trials showed that human milk oligosaccharides (2'-fucosyllactose, melting point about 230°C), mannitol (Pearlitol 160C, melting point about 165°C), and pregelatinized starch (Lycatab PGS, melting point about 257°C) were also suitable for producing granules with processing times greater than 1 hour. However, granules formed with Lycatab PGS were less soluble. Pregelatinized starch is therefore not preferred. Non-granulated inulin is similarly not preferred. Trials with Inulin HSI® (highly soluble inulin powder) did not allow processing times greater than 1 hour due to torque overload. Microcrystalline cellulose (melting point about 250° C.) is similarly undesirable. Although Avicel PH200 is dispersible in water, it is not water soluble.

Claims

1. A mixture comprising a filler, a binder and microcapsules, the mixture comprises 0.1% to 55% by weight of microcapsules based on the total weight of the mixture; and the mixture comprises 5% to 15% by weight of a binder, based on the total weight of the mixture; and the weight ratio of the filler to the binder is from 4:1 to 10:1; and The melting temperature of the binder is lower than the melting temperature of the filler; and A mixture in which the melting temperature of the filler is 151°C to 240°C.

2. The mixture of claim 1 , wherein the filler is a polysaccharide.

3. 3. The mixture of claim 1 or 2, wherein the binder is a polyol.

4. 3. The mixture of claim 1 or 2, wherein the filler is a dietary fiber and the binder is a sugar alcohol.

5. 3. The mixture according to claim 1, wherein the filler is inulin and the binder is sorbitol or ribose.

6. 3. The mixture of claim 1 or 2, wherein the weight ratio of the filler to the binder is from 5:1 to 10:

1.

7. 3. The mixture according to claim 1 or 2, wherein the microcapsules encapsulate a fat-soluble active ingredient.

8. 3. The mixture according to claim 1, wherein the microcapsules encapsulate at least two fat-soluble active ingredients.

9. The mixture - microcapsules containing vitamin A and / or - microcapsules containing vitamin E and / or microcapsules containing beta-carotene and / or - microcapsules containing vitamin D and / or -Microcapsules containing vitamin K 3. The mixture of claim 1 or 2, comprising:

10. 3. The mixture of claim 1 or 2, wherein the mixture comprises less than 10% by weight of water, based on the total weight of the mixture.

11. Granules comprising the mixture of claim 1 or 2.

12. Granules comprising the mixture of claim 1 or 2.

13. 12. Granules according to claim 11, wherein the granules have a mass median particle size D50 (volume based) of 0.5 mm to 6 mm, as measured using dynamic image analysis.

14. The granules according to claim 11, wherein the granules are obtained by continuous melt granulation of the mixture.

15. 12. The granules of claim 11, wherein the granules are water-soluble or water-dispersible.

16. 3. Use of the mixture according to claim 1 or 2 for continuous melt granulation.

17. 3. A method for producing granules, comprising feeding the mixture of claim 1 or 2 into an extruder.

18. 18. The method of claim 17, wherein the extruder is a twin-screw extruder without a cutting device.

19. 18. The method of claim 17, wherein the method does not include cutting the extruded strands.

20. 18. The method of claim 17, wherein the extruder has at least one kneading zone, and the at least one kneading zone is heated to a temperature of from 90°C to 150°C.