Active ingredient encapsulation system

Abstract

Disclosed is a system for encapsulating an active ingredient in a polymer matrix.

Description

[0001] ACTIVE INGREDIENT ENCAPSULATION SYSTEM

[0002] Disclosed is a system for encapsulating an active ingredient in a polymer matrix. The encapsulation system and the active ingredient are characterised by specific particle sizes, and a specific ratio between said sizes.

[0003] PRIOR ART

[0004] Products containing active ingredients whose release must be controlled during consumption, such as sweeteners, colourings, vitamins, minerals, caffeine, or active pharmaceutical ingredients in general, are known. In particular, in the case of sweeteners, as described in W02006 / 127074, encapsulation can be useful to modulate and prolong release with the aim of improving the flavour of the end product over a prolonged time, by using an encapsulating material and maintaining the tensile strength of the composition described above at a level exceeding 6500 PSI. Paragraph 63, in particular, indicates a close correlation between tensile strength and timing of the release of the active ingredient: the greater the tensile strength, the slower the release time of the encapsulated substance. Although the technology reported in W02006 / 127074 is theoretically applicable to all foods, its preferred application is in chewing gum (see paragraph 9), the bolus of which is chewed for many minutes.

[0005] It is also known that the encapsulating materials used (e.g. polyvinyl acetate and PVAc) are more effective to ensure slow release of the active ingredient if they have a high molecular weight; the higher the molecular weight, the longer the release time. Another controlled-release technique is described in W02006 / 127053 which, while recognising the concept that high- molecular-weight substances are more effective for slow release, also introduces the parameters of tensile strength (at least 6500 psi) and a range of water absorption capacity values (0.01% to 50% by weight).

[0006] In the various prior art documents, the lower threshold of tensile strength is therefore 6500 psi. WO 2005 / 051427 in particular describes an encapsulation system whose efficacy is based on tensile strength, measured according to ASTM-D638. In said document, the tensile strength ranges from 6500 to 200,000 psi.

[0007] The documents cited clearly indicate that numerous variables give rise to the efficacy of an encapsulation system for active ingredients, but the common factors are a tensile strength value above 6500 psi, and the general concept that a high-molecular-weight PVAc gives a better result in terms of release times.

[0008] However, in the case of confectionery products like chewing gum, the acceptability of a formulation to the end user does not only depend on prolonging the final flavour or prolonging the release of functional ingredients in general. Equally important parameters for acceptability are the hardness and roughness of the bolus during chewing. The roughness of the bolus changes during chewing, so that it is perceived as increasingly smooth. A bolus which is not very smooth may be associated with the presence of granular foreign bodies, leading to refusal to use the product again. The technical problems associated with the use of PVAc therefore remain, as the use of encapsulation systems comprising high-molecular-weight PVAc in a chewing gum formulation can give rise to unpleasant sensations on the tongue, such as excessive roughness or hardening of the bolus.

[0009] DESCRIPTION OF THE INVENTION

[0010] It has now been found that it is possible to solve the problems described above, and obtain an active ingredient encapsulation system comprising a matrix with medium-molecular- weight polyvinyl acetate (PVAc), while still maintaining release times comparable with those of a system containing high-molecular-weight PVAc, with the further advantage of obtaining a product with a higher level of smoothness during consumption.

[0011] A further advantage of using a PVAc with a lower molecular weight is that it considerably reduces the amount of emulsifiers required to obtain an acceptable product.

[0012] The encapsulation system according to the invention is effective due to the use of a medium-molecular-weight PVAc combined with a specific particle size ratio between the system and the encapsulated powder of the active ingredient.

[0013] In one embodiment of the present invention, a medium-molecular-weight PVAc can be advantageously used as the active ingredient encapsulating agent if the tensile strength values of the entire encapsulation system (< 6000 psi, unlike the teachings of the cited patents W02006 / 127053, W02006 / 127074 and WO 2005 / 051427), and the particle size values of the active ingredient and the polyvinyl acetate, are kept under control.

[0014] Said characteristics give the encapsulation system the desired release timing without any sensory repercussions.

[0015] The term “encapsulation system” means an oral drug-delivery system involving a combination of a polymer matrix and at least one active ingredient, which is at least partly encapsulated in the polymer matrix. The term also includes other substances which can be used to form the oral drug-delivery system (such as solvents, plasticisers, additives, colourings, etc.). The encapsulation system described above may not be the only one in the finished product (e.g. confectionery products).

[0016] The term “medium molecular weight” relating to polyvinyl acetate indicates a molecular weight range of 30000-60000 daltons determined, for example, by Gel Permeation Chromatography (GPC) techniques.

[0017] The term “active ingredient” relates to any encapsulated material included in the system described in the invention, wherein the active ingredient provides some properties required at the time of release from encapsulation (for example, when the encapsulated material is chewed). Examples of active ingredients include surfactants, limescale removers, hydrolytic agents (such as enzymes), bleaching agents, antibacterial agents, anticaries agents, tooth remineralisation agents, breath-freshening agents, plaque acid buffering agents and sweeteners (such as high- intensity sweeteners). Other examples of suitable active ingredients include flavourings, medicaments, vitamins, flavour masking agents, etc.

[0018] In particular, examples of high-intensity sweeteners comprise acesulfame K, aspartame, cyclamates, sucralose, thaumatin, neohesperidin DC, neotame, advantame, aspartameacesulfame salt, steviol glycosides, mogrosides, miraculin and monellin.

[0019] The term “tensile strength” refers to the maximum stress that a material can withstand while being stretched or pulled before breaking. A standard method for measuring the tensile strength of a given substance is defined by the American Society of Testing Materials in method ASTM-D638.

[0020] The term “encapsulating material” relates to one or more edible materials able to form a solid coating, such as an enveloping excipient or a film used as protective barrier around the active ingredient. The encapsulating material forms a matrix with a partly or completely encapsulated active ingredient; said material can also encapsulate a plurality of active ingredients.

[0021] The term “smoothness” refers to the properties of a food product and the bolus originating from said product during chewing, the surface of which is smooth and regular, ie. with no holes, lumps or rough areas that create an unpleasant sensation on the tongue and / or palate.

[0022] The subject of the invention is therefore an encapsulation system with a tensile strength < 6000 psi, preferably < 4000 psi, comprising a polymer matrix having a medium-molecular- weight polyvinyl acetate (PVAc) and at least one active ingredient encapsulated in the polymer matrix, said active ingredient having a particle-size distribution characterised by a median distribution equal to or less than l / 5th of the median particle-size distribution of said encapsulation system.

[0023] The encapsulation system preferably has a particle-size distribution characterised by a median ranging between 180 microns and 500 microns. The active ingredient powder to be encapsulated preferably has a particle-size distribution characterised by a median of less than 30 microns, more preferably less than 15 microns, and most preferably less than 10 microns. The encapsulation system has a performance better than or equal to that obtained with high- molecular-weight materials, without technical problems such as reduced smoothness.

[0024] For the purposes of the present invention, the particle-size distribution can be measured by any of the methods known to the skilled person. Laser light scattering techniques are preferred due to the completeness of the response, and sieves due to their cheapness and simplicity of use. In particular, an instrument such as a laser diffractometer can be used to determine the median and also other parameters, which are displayed directly by the software of the instrument. Using the sieving technique, if sieves are used to eliminate the fine and coarse fractions of the encapsulation system, the median particle-size distribution falls into the micron range corresponding to the range between the aperture of the fine sieve mesh and the aperture of the coarse sieve mesh.

[0025] The system according to the invention preferably comprises a single emulsifier in an amount less than or equal to 3% by weight, in particular a distilled monoglyceride with monoglyceride > 85%, also known as glycerol monostearate (GMS).

[0026] A further subject of the invention is a confectionery product containing the encapsulation system as described herein.

[0027] The invention is illustrated in greater detail in the experimental section below, wherein a high-intensity sweetener is used as active ingredient.

[0028] Table 1 shows the details of five encapsulation system compositions, indicating the percentages of polymer, in particular PVAc (polyvinyl acetate), GMS (glycerol monostearate) and sweetener. High-intensity sweeteners were used, but any active ingredient can be encapsulated in said system. Solid active ingredients in powder form are preferred. The encapsulation system compositions, including those shown in Table 1 and the following tables, are obtained by known methods such as mixing in a double-Z mixer, Banbury mixer or single- or twin-screw extruders, followed by suitable cooling, grinding and screening.

[0029] Table 1 As will be seen, two types of PVAc are used in the formulations; PVAc B30 has a molecular weight of 45-55000 daltons measured by GPC, while PVAc B100 has a molecular weight of 90000 daltons measured by SEC. This allowed samples containing a medium- molecular-weight polymer (45-55000 D in El, E3 and E5) and samples with a high-molecular- weight polymer (90000 D in E2 and E4) to be compared.

[0030] The five compositions of the encapsulation system have a particle-size distribution characterised by a median ranging between 180 microns and 500 microns.

[0031] The median particle-size distribution of the sweetener is set out below:

[0032] Sucralose: 2.3 microns (active ingredient: encapsulation system = 1 :78-217)

[0033] Aspartame: 13 microns (active ingredient: encapsulation system = 1 : 14-38) Acesulfame: 25 microns (active ingredient: encapsulation system = 1 :7-20) The five compositions of the encapsulation system shown in Table 1 were inserted in a sugar-free chewing gum with a composition according to the prior art, either fruit-flavoured (Table 2) or mint-flavoured (Table 3).

[0034] Compositions 2023-Encap. trial 1 - (2023 El) and 2023-Encap. trial 3 - (2023 E3) were also made with a particle-size distribution of the encapsulation system characterised by a median ranging between 40 microns and 50 microns. In this case, the compositions are identified as 2023-Encap. trial IF - (2023 E1F) and 2023-Encap. trial 3F - (2023 E3F), by reference to these two particular compositions:

[0035] Aspartame: 13 microns (active ingredient: encapsulation system = 1 :3-4)

[0036] Acesulfame: 25 microns (active ingredient: encapsulation system = 1 : 1.6-2)

[0037] The compositions of encapsulation system 2023-Encap. trial IF - (2023 E1F) and 2023- Encap. trial 3F - (2023 E3F) were inserted in a sugar-free chewing gum with a composition according to the prior art, fruit-flavoured only (Table 2).

[0038] Table 2

[0039] The total of the percentages indicated in the table does not amount to 100, because the percentages of the other ingredients required to make a chewing gum are not shown (such as gum base, sweeteners and flavourings, which do not affect the efficacy of the encapsulation system in any way). In general, the chewing gum compositions and the corresponding methods of obtaining them are those known to the skilled person and in the prior art. Also in Table 2 and the subsequent tables, where present, k Apm=aspartame and AceK=acesulfame K. Control 2023-G1 : this is a recipe according to the prior art wherein “free” acesulfame K and “free” aspartame are included directly in the chewing gum composition, without any encapsulation system.

[0040] Test 2023-G2 is one of the possible embodiments of the invention; in this recipe, acesulfame and aspartame are supplied as encapsulated sweeteners with medium-molecular- weight PVAc (codes 2023-E1 plus 2023-E3). The net amount of acesulfame in Test 2023-G2 is the same as in Control 2023-G1, and the net amount of aspartame in Test 2023-G2 is the same as in Control 2023-G1. Other bulk sweeteners are present in the same amounts, or with negligible adjustments.

[0041] Test 2023-G2F has the same composition as Test 2023-G2; however, the encapsulated sweeteners (codes 2023-E1F plus 2023-E3F) do not reflect the ratio between the medians according to the invention.

[0042] Test 2023-G3, comparative sample: in this recipe, acesulfame and aspartame are supplied as sweeteners encapsulated with high-molecular- weight PVAc (codes 2023 -E2 plus 2023 -E4). The net amount of acesulfame in Test 2023 -G3 is the same as in Control 2023 -Gl, and the net amount of aspartame in Test 2023-G3 is the same as in Control 2023-G1. Other bulk sweeteners are present in the same amounts, or with negligible adjustments.

[0043] Test 2023-G4 is one of the possible embodiments of the invention; in this recipe, sucralose is supplied as sweetener encapsulated with medium-molecular-weight PVAc (codes 2023-E5). The net amount of sucralose in Test 2023-G4 was proportioned to provide the same theoretical sweetness as the sum of aspartame + acesulfame K in Control 2023-G1. Other bulk sweeteners are present in the same amounts, or with negligible adjustments. Thus according to the data in the literature, Test 2023-G4 should be as sweet as Control 2023-G1. The same obviously applies to tests 2023 -G2 and 2023 -G3.

[0044] When the sucrose is as described in definition 1, the potency of each sweetener is aspartame 320, acesulfame 320, sucralose 600. Said values are multiplied by the net % of each sweetener to calculate the equivalent sweetness of each sweetener in a formula, and then added together to obtain the total equivalent sweetness attributed to the high-intensity sweeteners.

[0045] The gums used in the test were made in the form of sticks, and tested by 11 trained members of a panel of tasters. The perception of sweetness for 20 minutes is shown in the graph in Fig. 1. In the first 7 minutes, the sweetness of Control 2023-G1 was greater than that of all the other chewing gums containing encapsulated sweeteners. At about 7 minutes, the sweetness of 2023 -G4 with sucralose encapsulated according to the invention in medium-molecular- weight PVAc crosses Control 2023-G1. From that time onwards, the gum with encapsulated sweetener is sweeter than the control. At about 9 minutes, the sweetness of 2023-G2 with acesulfame K and aspartame encapsulated according to the invention in medium-molecular- weight PVAc crosses Control 2023-G1. From that time onwards, said gum with encapsulated sweetener is sweeter than the control. At about 12 minutes, the sweetness of 2023-G3 with acesulfame K and aspartame encapsulated according to the prior art in high-molecular-weight PVAc crosses Control 2023-G1. From that time onwards, said gum with encapsulated sweetener is sweeter than the control. Moreover, the perception of sweetness after the last crossing at 12 minutes will always be 2023-Gl<2023-G3<2023-G2<2023-G4 (see Fig. 2).

[0046] The graph in Fig. 1 and the chart in Fig. 2 also show the sweetness of Test gums 2023- G2F; said gums have the same composition as Test 2023 -G2, but the perception of sweetness is similar to that of Control 2023-G1, ie. the gums containing the composition according to the invention are sweeter in the first few minutes, while from minute 10 onwards, Test 2023 -G2F is less sweet than Test 2023-G2 and Test 2023-G4.

[0047] This means that the sweeteners encapsulated according to the invention are more effective in maintaining the perceived sweetness level during the final stage of consumption than the control sample and the sweeteners encapsulated with high-molecular-weight PVAc according to the prior art. The results are obtained over the time necessary to demonstrate the long-lasting effect (within 20 minutes). The best results are obtained with sucralose, the sweetener with the highest ratio of mean particle size between active ingredient and encapsulation system. Control 2023-G1 is obviously sweeter in the first few minutes because it contains “free” sweeteners, which are released more rapidly. The behaviour of Test 2023-G2F is believed to be similar to that of Control 2023-G1 because the lower ratio of mean particle size between active ingredient and encapsulation system causes a significant proportion of active ingredient to be exposed to the surface of the system, and therefore to be dissolved by the saliva, similarly to the same active ingredient in “free” form.

[0048] To obtain a product with the ideal level of sweetness during consumption (from the first few seconds until the end of chewing), parts of free sweeteners can be combined with parts of sweeteners encapsulated according to the invention to provide initial and long-lasting sweetness.

[0049] The five compositions of the encapsulation system were inserted in peppermint- flavoured chewing gum (Table 3).

[0050] Table 3

[0051] Once again, the total of the percentages indicated in the table does not amount to 100 because it does not include the percentages of the other ingredients needed to create a gum according to the prior art (such as gum base, sweeteners and flavourings, which do not affect the efficacy of the encapsulation system in any way).

[0052] The samples were evaluated in terms of sweetness as in the preceding case, using a test panel characterised by the same parameters, the results of which are summarised in Figure 3.

[0053] During the first few minutes of chewing, the sweetness of Control 2023-G5 is greater than that of both the chewing gums with encapsulated sweeteners. However, from minute 3 onwards, chewing gum 2023 -G6 according to the invention (containing sweeteners encapsulated with medium-molecular weight PVAc) is sweeter than both Control 2023-G5 (with free high-intensity sweeteners) and Test 2023-G7 (containing sweeteners encapsulated with high-molecular-weight PVAc). The same samples were also evaluated in terms of smoothness (Figure 4).

[0054] The control gum is smoother on the whole than the chewing gums with encapsulated sweeteners. However, from minute 5 onwards, the smoothness of Test 2023-G6 with medium- molecular-weight PVAc increases, approaching that of the control, whereas the smoothness of Test 2023-G7 with high-molecular-weight PVAc remains constant.

[0055] The latter test demonstrates that a chewing gum containing an encapsulation system according to the invention not only solves the problems involved in obtaining a product having a long-lasting effect of the active ingredient selected (in this case a sweetener), but also the problems associated with the smoothness of the product as defined above.

[0056] Method ASTM D638 IV was used to verify the mechanical properties of the encapsulated sweetener. The results are summarised in Table 4.

[0057] Table 4 All tests demonstrated a maximum breaking load < 6500 psi, preferably < 5000 psi (Fig.

[0058] 5). To further demonstrate the efficacy of the encapsulation system according to the invention, other tests were conducted to measure smoothness, hardness and sweetness.

[0059] The characteristics of the encapsulation system tested were as follows:

[0060] The encapsulation system has a particle-size distribution characterised by a median ranging between 300 and 500 microns, while the aspartame has a particle-size distribution characterised by a median of 13 microns (active ingredient: encapsulation system ratio 1 :23- 38). The sweeteners thus encapsulated were included in the chewing gum according to the following recipes, bearing in mind that 100% of the composition is arrived at by adding the gum base, other sweeteners and flavourings.

[0061] The samples were evaluated as in the preceding case, with particular attention to smoothness and sweetness in the 20-minute chewing period. The results are shown in Figures 6 and 7 :

[0062] Smoothness (Figure 6): the control sample always remains the smoothest chewing gum, while Test 2023-G18 with high-molecular-weight PVAc is the least smooth throughout the chewing time. Test 2023-G20, made according to the invention, maintains an intermediate position, starting like Test 2023-G18 with high-molecular-weight PVAc, but gradually reaches the same smoothness as the control after 20 minutes’ chewing.

[0063] Sweetness (Figure 7): the smoothness results are not achieved at the expense of sweetness. The control is the sweetest chewing gum until minute 7 (this is due to the release of free aspartame, which is faster than the encapsulated equivalent), while Test 2023-G18 with high-molecular-weight PVAc is the least sweet chewing gum from minute 3 onwards. Test 2023-G20 with medium-molecular-weight PVAc is sweeter than Test 2023-G18 from minute

[0064] 5 onwards and sweeter than the control from minute 15 onwards, and is clearly the best in terms of long-lasting sweetness.

Claims

CLAIMS1. An encapsulation system for oral administration with a tensile strength < 6000 psi measured according to method ASTM-D638, comprising a polymer matrix comprising or consisting of medium-molecular-weight polyvinyl acetate and at least one active ingredient encapsulated in the polymer matrix, said ingredient having a particle-size distribution characterised by a median distribution equal to or less than l / 5th of the median particle-size distribution of said encapsulation system.

2. The system according to claim 1 having a particle-size distribution characterised by a median ranging from 180 microns to 500 microns.

3. The system according to claim 1 or 2 wherein the active ingredient is in powder form and has a median particle-size distribution of less than 30 microns, preferably less than 15 microns, and more preferably less than 10 microns.

4. The system according to any one of the preceding claims wherein the active ingredient is a high-intensity sweetener selected from acesulfame K, aspartame, cyclamates, sucralose, thaumatin, neohesperidine DC, neotame, advantame, aspartameacesulfame salt, steviol glycosides, mogrosides, miraculin and monellin.

5. The system according to any one of the preceding claims including a single emulsifier in an amount less than or equal to 3% by weight.

6. The system according to claim 5 wherein the emulsifier is a distilled monoglyceride with monoglyceride > 85% by weight of the distilled monoglyceride.

7. A confectionery product containing an encapsulation system according to any one of the preceding claims.

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