Flow pack for oral delivery of active ingredients

Abstract

The present invention relates to a flow pack for oral delivery of an active ingredient comprising a population of particles and one or more active ingredients, wherein the population of particles comprises at least two types of sugar alcohol particles, and at least one of the two types of sugar alcohol particles comprises i) granulated sugar alcohol particles.

Description

Technical Field

[0001] The present invention relates to the field of flow packs containing powder delivery systems suitable for oral delivery of active ingredients. In particular, the present invention relates to sugar alcohol delivery systems containing one or more active ingredients.

Background Art

[0002] For the administration of pharmaceutical active ingredients and active ingredients having health promotion benefits, oral tablets have conventionally been preferred. In terms of both convenience and compliance, oral tablets have certain advantages compared to other delivery vehicles for oral administration of active ingredients. Further benefits include the uniformity of the contents, which is particularly important for pharmaceutical active ingredients where the lack of safety and proper delivery can be fatal in the alleviation or treatment of medical conditions.

[0003] Oral tablets for gastrointestinal and oral mucosal delivery of active ingredients are also generally preferred in terms of ensuring an appropriate route of administration. Typically, such oral tablets are produced by direct compression or compaction methods that press a powder tablet material and an active ingredient into a defined tablet with an appropriate strength, providing a pharmacological effect to patients who need it in medical formulations or a health benefit to consumers in nutritional supplements.

[0004] Despite efforts to formulate oral tablets and improvements heretofore, the oral tablets known heretofore have various drawbacks. For example, since the active ingredient is usually released from the oral tablet over time, there may be an essentially delayed time from the administration of the oral tablet to the full efficacy of the active ingredient. This is applicable, for example, when the tablet is designed for buccal absorption or gastrointestinal delivery. Different improved tablets such as orally disintegrating tablets aimed at disintegrating the tablet relatively quickly have been provided. However, these tablets may only help solve the problem of delay and may not solve it.

[0005] Furthermore, formulating the active ingredient into an oral tablet may significantly impair convenience for certain consumers. Here, for example, individuals with dry mouth or reduced saliva production may have difficulty swallowing tablets. Ultimately, this could lead to inadequate treatment for medical patients and insufficient health benefits for consumers of the nutritional supplement.

[0006] In particular, the potential benefits of obtaining release characteristics for active ingredients that enhance convenience and efficacy have not received much attention. One of these release characteristics is increased saliva production. The experience of increased saliva production, especially increased saliva production upon administration, may have some significant benefits, for example, in the delivery of active ingredients to mucosal surfaces.

[0007] Furthermore, it is preferable to provide formulations that may also help to obtain improved sensory characteristics for active ingredient delivery. Here, important sensory characteristics include mouthfeel, mouth dissolution, flavor, saliva production, cooling sensation, and off-note sensations associated with the active ingredient. These characteristics are important not only from the standpoint of convenience in oral administration, but also certainly important for supporting proper delivery of the active ingredient and avoiding adverse side effects of the active ingredient. Mouthfeel in particular is one of the more important sensory characteristics for active ingredient delivery, separate from efficacy.

[0008] One challenge with oral tablets as a delivery vehicle for active ingredients is that some active ingredients tend to produce off-notes during administration due to their specific physicochemical properties. The challenge of taste masking is more pronounced when more release of such active ingredients is required. If the off-note is the dominant sensation during administration, it can affect convenience and, more importantly, the delivery of such active ingredients. [Prior art documents] [Patent Documents]

[0009] [Patent Document 1] International Publication No. 00 / 25598 [Non-patent literature]

[0010] [Non-Patent Document 1] Martindale, The Extra Pharmacopoeia, 28th edition, pp. 547-578. [Non-Patent Document 2] J. Dent.Res, Vol.28, No.2, pp. 160-171, 1949 [Non-Patent Document 3] U.S. Federal Code of Regulations, Title 21, Sections 182.5013.182 5997 and 182.8013-182.8997 [Non-Patent Document 4] Pharm. Int., Nov. 85, pp. 267-271, Barney H. Hunter and Robert L. Talbert [Overview of the Initiative] [Problems that the invention aims to solve]

[0011] Therefore, the prior art presents a need for an improved administration platform that solves the problems and issues of the prior art mentioned above. In particular, there is a need in the art for a novel platform that supports improved saliva production and appropriate delivery of active ingredients combined with beneficial sensory properties. [Means for solving the problem]

[0012] The present invention relates to a novel powder delivery system contained in a flow pack rather than in tablet form. In particular, the present invention provides a flow pack for oral delivery of an active ingredient comprising a group of particles and one or more active ingredients, wherein the group of particles comprises at least two types of sugar alcohol particles, and at least one of the two types of sugar alcohol particles comprises i) granulated sugar alcohol particles (granulated sugar alcohol particles).

[0013] Generally, unlike conventional oral tablets, the powder system of the present invention may offer various advantages in terms of various other properties, such as sensory properties and release properties. The powder system is designed to encompass a synergistic combination of different types of sugar alcohol particles. The combined different types of sugar alcohol particles function to deliver the active ingredient with improved efficacy and to address various sensory advantages compared to conventional oral tablets, including an improved mouthfeel. Furthermore, the powder system aims to be superior to simpler and less complex powder systems available for administering the active ingredient.

[0014] The inventors of the present invention did not anticipate that combining at least two sugar alcohol particles according to the present invention would solve various prior art problems relating to oral tablets and simpler powder delivery systems. Such problems include improved saliva production and proper delivery of active ingredients combined with beneficial sensory properties.

[0015] In particular, the present invention may be useful in obtaining release characteristics of the active ingredient that result in improved convenience and efficacy. One of these release characteristics is increased saliva production. The experience of increased saliva production, especially increased saliva production during administration, may have several significant advantages, for example, for the delivery of the active ingredient to the mucosal surface.

[0016] Furthermore, the present invention may help to obtain improved sensory characteristics of active ingredient delivery. Here, important sensory characteristics include mouthfeel, mouth-melting sensation, flavor, saliva production, cooling sensation, and off-note sensations associated with the active ingredient or processing aids. Of particular interest is providing a mouthfeel suitable for giving a more acceptable treatment or symptom relief to healthcare patients or consumers seeking health benefits. The present invention may also help to improve the masking of off-note tastes during administration. The challenge of taste masking is more pronounced when a greater release of such active ingredients is achieved, which generally applies to the powder delivery systems of the present invention.

[0017] In one aspect of the present invention, there is provided a flow pack for oral delivery of a population of particles and one or more active ingredients, wherein the population of particles comprises at least two types of sugar alcohol particles, and at least one of the two types of sugar alcohol particles comprises i) granulated sugar alcohol particles (granulated sugar alcohol particles), and the population of particles comprises at least two types of sugar alcohol particles comprising i) granulated sugar alcohol particles and ii) non-directly compressible (non-DC) sugar alcohol particles.

[0018] The combination of granulated sugar alcohol particles and non-directly compressible (non-DC) sugar alcohol particles according to the present invention can provide advantages that conventional powder systems cannot. One such advantage is an improved mouthfeel. Another is improved saliva production. According to the present invention, the powder delivery system may change to a liquid relatively quickly, i.e., may liquefy relatively quickly. Other advantages may include an improved melt-in-the-mouth feeling, flavor sensation, cooling sensation, and an improvement in off-note sensations associated with the active ingredient.

[0019] In another aspect of the present invention, there is provided a flow pack for oral delivery of a population of particles and one or more active ingredients, wherein the population of particles comprises at least two types of sugar alcohol particles, and at least one of the two types of sugar alcohol particles comprises i) granulated sugar alcohol particles, and the population of particles comprises at least two types of sugar alcohol particles comprising i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles.

[0020] The combination of granulated sugar alcohol particles and directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles according to the present invention can provide advantages that conventional powder systems cannot. One such advantage is an improved mouthfeel. Another is improved cooling. Other advantages may include an improved melt-in-the-mouth feeling, saliva secretion, flavor sensation, and an improvement in off-note sensations associated with the active ingredient.

[0021] In yet another aspect of the invention, a flow pack for oral delivery of a population of particles and one or more active ingredients is provided, wherein the population of particles comprises at least two types of sugar alcohol particles, at least one of the two types of sugar alcohol particles comprises i) granulated sugar alcohol particles, and the population of particles comprises at least three types of sugar alcohol particles comprising i) granulated sugar alcohol particles, ii) non-direct compressibility (non-DC) sugar alcohol particles, and iii) direct compressibility (DC) sugar alcohol particles that are not granulated sugar alcohol particles.

[0022] The unique combination of granulated sugar alcohol particles, non-direct compressibility (non-DC) sugar alcohol particles, and direct compressibility (non-DC) sugar alcohol particles that are not granulated sugar alcohol particles according to the present invention can provide additional advantages that conventional powder systems cannot provide. One such advantage is an improved mouthfeel. Another is improved saliva production. Yet another advantage is an improved cooling sensation. Other advantages may include an improved melt-in-mouth feeling, flavor sensation, and off-note sensation associated with the active ingredient.

[0023]

[0024] ​In the context of this specification, when a powder delivery system is said to be “dry and flowable,” the intended meaning is that the system behaves as a powder in such a way that its moisture content is sufficiently low that a person skilled in the art of powder technology would consider it “dry” for the purposes of the present invention, and that it is “flowable” for the purposes of the present invention. For example, the system does not need to have a specific moisture content of 0.0%, but may have a moisture content such that it behaves as a powder for the purposes of the present invention, e.g., less than 10.0% by mass, 8.0% by mass, 6.0% by mass, 4.0% by mass, 2.0% by mass, 1.5% by mass of water, e.g., less than 1.0% by mass.

[0025] In terms of being "flowable," the powder delivery systems according to the present invention in some embodiments do not need to be "freely flowable." In some embodiments, it is appropriate that the powder be "flowable" in the sense that certain aggregation of particles is acceptable and not all types of particles in the powder delivery system are free-flowable. For example, some degree of aggregation during storage is acceptable, but the powder can be handled gently and made flowable to a certain extent. To avoid concern, tablets are not considered "flowable" in the context of this specification. Therefore, the powder delivery systems according to the present invention are neither tablets, such as chewable tablets or orally disintegrating tablets according to the present invention, nor are they contained within tablets.

[0026] In some embodiments of the present invention, the powder delivery system is a collection of dry, substantially free-flowing particles.

[0027] In some embodiments of the present invention, the powder delivery system is a collection of dry, free-flowing particles.

[0028] In some embodiments of the present invention, at least one of at least two sugar alcohol particles having different particle size distributions is substantially fluid.

[0029] In some embodiments of the present invention, at least one of at least two sugar alcohol particles having different particle size distributions is fluid.

[0030] In some embodiments of the present invention, at least two of the at least two sugar alcohol particles having different particle size distributions are substantially free-flowing.

[0031] In some embodiments of the present invention, at least two of the at least two sugar alcohol particles having different particle size distributions are free-flowing.

[0032] In some embodiments of the present invention, all of at least two types of sugar alcohol particles having different particle size distributions are substantially free-flowing.

[0033] In some embodiments of the present invention, all of the at least two sugar alcohol particles having different particle size distributions are free-flowing.

[0034] In the context of this specification, the term “rinsable” is intended to be understood as forcibly circulating the powder delivery system within the oral cavity, or forcibly circulating the liquid generated shortly thereafter within the oral cavity. The term “rinsable” may also encompass “gargle,” “circle,” or “push and circulate,” or similar expressions. The powder delivery system and the generated fluid may be distributed within the oral cavity to the oral mucosa, tongue, and teeth in a manner that ensures contact with the oral cavity surface. Furthermore, during “rinsing,” to mimic a liquid mouthwash, a small amount may be swallowed while retaining most of the saliva generated in the oral cavity, although some of the generated liquid may not be swallowed during operation. Typically, this system is strong enough to avoid the need to add further water. However, some water may be added, but it is not necessary to realize the advantages of the present invention.

[0035] In the context of this specification, “fluid” or “fluid generation” or similar terms should be understood in relation to the present invention as “saliva” or “saliva generation” as a result of administration of the powder delivery system according to the present invention. Thus, standard saliva generation is not intended, but excessive saliva generation directly caused by the powder delivery system is part of the context. When it is said that the particle collection mimics a liquid mouthwash, the intended meaning is that enough liquid is generated to provide the same or improved oral care benefits as a liquid mouthwash. According to the present invention, the same amount of liquid used in a liquid mouthwash is not required, as long as the amount of saliva generated is manageable for “rinsing.” However, in some cases, the amount of saliva generated may be at the same level as that achieved by using a liquid mouthwash.

[0036] It should be noted that, with respect to the “oral care benefits” as used in the context of this specification, these effects will be understood by those skilled in the art to include specific benefits such as stain removal benefits, bad breath benefits, plaque removal benefits, whitening benefits, and reduction or treatment of gingivitis. All of these conditions may be addressed in accordance with the present invention, or one or more of these conditions may be addressed. Furthermore, in the context of this specification, conditions other than “oral care benefits” may also be included. In addition, conditions in the throat may be addressed by the present invention, or conditions in the digestive tract may be addressed.

[0037] In some embodiments of the present invention, rinsing with the powder delivery system is characterized by forcibly rotating the powder delivery system in the mouth over a period of time.

[0038] In some embodiments of the present invention, rinsing the powder delivery system is characterized by forcibly rotating the powder delivery system in the mouth for at least 5 seconds. In some embodiments of the present invention, rinsing the powder delivery system is characterized by forcibly rotating the powder delivery system in the mouth for at least 10 seconds. In some embodiments of the present invention, rinsing the powder delivery system is characterized by forcibly rotating the powder delivery system in the mouth for at least 15 seconds. In some embodiments of the present invention, rinsing the powder delivery system is characterized by forcibly rotating the powder delivery system in the mouth for at least 20 seconds.

[0039] In some embodiments of the present invention, at least a portion of the fluid produced by rinsing with the powder delivery system is forcibly circulated in the oral cavity over a period of time.

[0040] Surprisingly, in some embodiments, the powder delivery system was able to dissolve relatively quickly in the oral fluid generated at the time of administration after oral administration. In some embodiments, the powder delivery system dissolves within 15 seconds. In some embodiments, the powder delivery system dissolves within 10 seconds. In some embodiments, the powder delivery system dissolves within 8 seconds. In some embodiments, the powder delivery system dissolves within 5 seconds.

[0041] In some embodiments of the present invention, at least a portion of the saliva produced by rinsing with the powder delivery system is forcibly swirled in the oral cavity for at least 10 seconds. In some embodiments of the present invention, at least a portion of the saliva produced by rinsing with the powder delivery system is forcibly swirled in the oral cavity for at least 20 seconds. In some embodiments of the present invention, at least a portion of the saliva produced by rinsing with the powder delivery system is forcibly swirled in the oral cavity for at least 30 seconds.

[0042] In some embodiments of the present invention, at least a portion of the fluid produced by rinsing with the powder delivery system is forcibly circulated in the mouth for a period of time before the portion of the fluid is swallowed or spat out, in order to provide oral care benefits.

[0043] In some embodiments of the present invention, the oral care benefit is obtained by rinsing at least a portion of the powder delivery system and / or the fluid generated in the oral cavity for at least 10 seconds. In some embodiments of the present invention, the oral care benefit is obtained by rinsing at least a portion of the powder delivery system and / or the fluid generated in the oral cavity for at least 10 seconds and at least 20 seconds. In some embodiments of the present invention, the oral care benefit is obtained by rinsing at least a portion of the powder delivery system and / or the fluid generated in the oral cavity for at least 30 seconds.

[0044] In some embodiments of the present invention, the powder delivery system is a collection of dry, flowable particles that are rinsed upon oral administration, generate a fluid in the oral cavity, and mimic a liquid mouthwash by optionally adding water.

[0045] In some embodiments of the present invention, the Hausner ratio of the powder delivery system is between 1.00 and 1.59. Generally, a ratio greater than 1.59 is considered undesirable in relation to this specification.

[0046] The Hausner ratio is known to those skilled in the art as the ratio between stamped powder (g / mL) and unstamped powder (g / mL). This ratio represents the ratio between the bulk densities of stamped and unstamped powders. The Hausner ratio is generally classified by its compressibility index and represents the fluidity of the powder. The best fluidity is obtained when the Hausner ratio is 1.00, and the higher the Hausner ratio, the lower the fluidity of the powder.

[0047] In some embodiments of the present invention, the Hausner ratio of the powder delivery system is 1.00 to 1.45.

[0048] In some embodiments of the present invention, the Hausner ratio of the powder delivery system is 1.00 to 1.34.

[0049] In some embodiments of the present invention, the Hausner ratio of the powder delivery system is less than 1.59, for example, less than 1.45.

[0050] In some embodiments of the present invention, the Hausner ratio of the powder delivery system is less than 1.34, for example, less than 1.25.

[0051] In some embodiments of the present invention, the powder delivery system generates more than 1.5 mL of fluid in the oral cavity within a period of 30 to 90 seconds from the start of administration.

[0052] In some embodiments of the present invention, the powder delivery system generates more than 1.5 mL of fluid in the oral cavity within a period of 90 to 180 seconds from the start of administration.

[0053] In some embodiments of the present invention, the powder delivery system generates more than 1.5 mL of fluid in the oral cavity within a period of 180 to 300 seconds from the start of administration.

[0054] In some embodiments of the present invention, the powder delivery system provides an improved cooling effect compared to a powder delivery system that does not contain at least one of at least two types of sugar alcohol particles having different particle size distributions.

[0055] In some embodiments of the present invention, the powder delivery system provides an improved watering effect compared to a powder delivery system that does not contain at least one of at least two sugar alcohol particles having different particle size distributions.

[0056] In some embodiments of the present invention, the powder delivery system provides an improved mouthfeel compared to a powder delivery system that does not include at least one of at least two types of sugar alcohol particles having different particle size distributions, the improved mouthfeel includes at least one of a less gritty mouthfeel, a less powdery mouthfeel, a less rough mouthfeel, a less viscous mouthfeel, or an improved texture.

[0057] The granulated sugar alcohol particles according to the present invention may, in themselves, offer various advantages compared to simpler powder delivery systems known in the art. One of these advantages of the granulated sugar alcohol particles according to the present invention is that they provide an improved mouthfeel despite having a relatively large particle size. Without being bound by theory, it is thought that the surface morphology and / or chemical composition of the granulated sugar alcohol particles according to the present invention may also act synergistically with indirectly compressible (non-DC) sugar alcohol particles and / or directly compressible (non-DC) sugar alcohol particles that are not granulated according to the present invention. Therefore, the advantages from all three types of particles may contribute to the overall benefits of the present invention, and their combination may result in further unexpected synergistic properties of the powder delivery system of the present invention.

[0058] In the context of this specification, the term “type of particle” or similar wording is intended to mean particles that differ in either surface morphology or chemical composition, unless otherwise specified. For example, two types of sugar alcohol particles may be granulated sugar alcohol particles and ungranulated sugar alcohol particles. In the broadest sense, both types of sugar alcohol particles may be granulated sugar alcohol particles, but differ in either surface morphology or chemical composition. Typically, when indirectly compressible (non-DC) sugar alcohol particles are present, or when directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles are present, the two types of particles are granules of different sugar alcohols, such as xylitol and erythritol, or sorbitol, respectively. Thus, the two types of particles may also include xylitol in granulated form and xylitol in ungranulated form.

[0059] In one embodiment of the present invention, the granulated sugar alcohol particles i) are directly compressible (DC) sugar alcohol particles.

[0060] The term "DC sugar alcohol particles" refers to particles of directly compressible (DC) sugar alcohols. Note that the terms "DC sugar alcohol particles" and "DC particles" are interchangeable. DC sugar alcohol particles may be obtained by granulating a non-DC sugar alcohol, for example, with another sugar alcohol or binder, for the purpose of obtaining so-called directly compressible particles (DC). This may be carried out by a wet granulation process or a dry granulation process. Furthermore, granulation of a non-DC sugar alcohol using water as a binder is considered to result in DC sugar alcohol particles in the context of this specification. The aggregation of particles into single particles is also within the intended meaning. Typically, DC sugar alcohol particles have a surface morphology that includes a coarse surface morphology when observed with a scanning electron microscope. In the context of this specification, "granulated," "granulated," "or aggregated," or similar terms are not intended to include grinding, pulverizing, or grinding larger crystalline particles into smaller particles.

[0061] The term “DC sugar alcohol particles that are not granulated sugar alcohol particles” refers to particles of directly compressible (DC) sugar alcohols that are not granulated but are essentially DC. Sorbitol particles are an example of such particles. Ungranulated dextrose, for example, ungranulated dextrose with an average particle size of less than 250 microns, e.g. less than 210 microns, e.g. less than 180 microns, e.g. less than 150 microns, is also considered an example of such particles. In the context of this specification, “granulated” or “granulated” or similar wording is not intended to include grinding, pulverizing, or grinding larger crystalline particles into smaller particles.

[0062] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, including i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles.

[0063] The term "non-DC sugar alcohol particles" refers to particles of non-directly compressible (non-DC) sugar alcohols. Note that the terms "non-DC sugar alcohol particles" and "non-DC particles" are used interchangeably. In the context of this specification, non-DC sugar alcohol particles refer to particles that have not been pretreated, for example, by granulation with other sugar alcohols or binders, for the purpose of obtaining so-called directly compressible particles (DC). Typically, non-DC sugar alcohol particles include particles obtained by crystallization, and optionally, possibly subsequent grinding, pulverization, or grinding without other sugar alcohols or binders. Therefore, non-DC sugar alcohol particles can be considered particles consisting of non-DC sugar alcohols. However, some impurities may be present. Therefore, particles can be considered to consist substantially of non-DC sugar alcohols. Similarly, non-DC sugar alcohol particles can be considered non-granulated sugar alcohol particles. Typically, non-DC sugar alcohol particles have a surface morphology that includes a smooth surface morphology when observed with a scanning electron microscope, compared to DC sugar alcohol particles.

[0064] In one embodiment of the present invention, non-DC sugar alcohol particles include crystalline sugar alcohol particles obtained by a crystallization process, optionally followed by grinding, micronization, or abrasion without other sugar alcohols or binders. In this context, “crystalline” is intended to mean that the individual particles consist of a coherent crystalline structure and not, for example, a microcrystalline structure in which small crystalline particles aggregate to form larger particles.

[0065] One advantage of the present invention is the remarkably strong saliva production compared to conventional formulations. In particular, non-DC particles remarkably induce significant saliva production. Increased saliva production can have a significant impact on the delivery of one or more active ingredients. Specifically, increased saliva production can increase the exposure of one or more active ingredients to the mucosal surface, thereby contributing to increased uptake in the oral mucosa. More specifically, if the increase in saliva production is initiated quickly, one or more active ingredients can be exposed to the mucosal surface relatively rapidly, thereby delivering the desired effect relatively quickly. Thus, according to the present invention, a synergistic effect can be observed between the uptake of active ingredients and increased saliva production. Non-DC erythritol is an example of a sugar alcohol that can significantly contribute to increased saliva production.

[0066] One unexpected advantage over prior art is the remarkably sustained saliva production even after the user has swallowed the bulk portion of the non-DC sugar alcohol. This sustained saliva production can be advantageous for many applications of the formulation, affecting mouthfeel, taste, and flavor perception.

[0067] In one embodiment of the present invention, the group of particles comprises at least two types of sugar alcohol particles, including i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles.

[0068] In one embodiment of the present invention, the group of particles comprises at least three types of sugar alcohol particles, including i) granulated sugar alcohol particles, ii) indirectly compressible (non-DC) sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles.

[0069] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and ii) indirectly compressible (non-DC) sugar alcohol particles having a particle size of less than 500 microns, where more than 80% of the particles are less than 500 microns.

[0070] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and ii) indirectly compressible (non-DC) sugar alcohol particles having a particle size of less than 400 microns for more than 50% of the particles.

[0071] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and ii) indirectly compressible (non-DC) sugar alcohol particles having a particle size of less than 400 microns for more than 80% of the particles.

[0072] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and ii) indirectly compressible (non-DC) sugar alcohol particles having a particle size of less than 250 microns for more than 50% of the particles.

[0073] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and ii) indirectly compressible (non-DC) sugar alcohol particles having a particle size of less than 250 microns for more than 80% of the particles.

[0074] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and ii) indirectly compressible (non-DC) sugar alcohol particles having a particle size of less than 250 microns for more than 95% of the particles.

[0075] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 500 microns for more than 80% of the particles.

[0076] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 500 microns for more than 95% of the particles.

[0077] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 400 microns for more than 80% of the particles.

[0078] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 400 microns for more than 95% of the particles.

[0079] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 300 microns for more than 80% of the particles.

[0080] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 300 microns for more than 95% of the particles.

[0081] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 100 microns for more than 70% of the particles.

[0082] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 100 microns for more than 80% of the particles.

[0083] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 100 microns for more than 95% of the particles.

[0084] In one embodiment of the present invention, the particle collection comprises at least three types of sugar alcohol particles, including i) granulated sugar alcohol particles, ii) indirectly compressible (non-DC) sugar alcohol particles having a particle size of less than 250 microns for more than 80% of the particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 300 microns for more than 80% of the particles.

[0085] In one embodiment of the present invention, the particle collection comprises at least three types of sugar alcohol particles, including i) granulated sugar alcohol particles, ii) indirectly compressible (non-DC) sugar alcohol particles having a particle size of less than 250 microns for more than 95% of the particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 100 microns for more than 80% of the particles.

[0086] In one embodiment of the present invention, the particle collection comprises at least three types of sugar alcohol particles, including i) granulated sugar alcohol particles, ii) indirectly compressible (non-DC) sugar alcohol particles having a particle size of less than 250 microns for more than 95% of the particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, having a particle size of less than 100 microns for more than 70% of the particles.

[0087] In one embodiment of the present invention, the particle collection comprises i) at least two types of sugar alcohol particles, each containing granulated sugar alcohol particles in an amount of at least 10% by mass of the particle collection.

[0088] In one embodiment of the present invention, the particle collection comprises i) at least two types of sugar alcohol particles, each containing granulated sugar alcohol particles in an amount of at least 20% by mass of the particle collection.

[0089] In one embodiment of the present invention, the particle collection comprises i) at least two types of sugar alcohol particles, each containing granulated sugar alcohol particles in an amount of at least 25% by mass of the particle collection.

[0090] In one embodiment of the present invention, the particle collection comprises i) at least two types of sugar alcohol particles, each containing granulated sugar alcohol particles in an amount of at least 30% by mass of the particle collection.

[0091] In one embodiment of the present invention, the particle collection comprises i) at least two types of sugar alcohol particles, each containing granulated sugar alcohol particles in an amount of at least 40% by mass of the particle collection.

[0092] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles in an amount of at least 10% by mass of the particle collection, and ii) indirectly compressible (non-DC) sugar alcohol particles in an amount of at least 10% by mass of the particle collection.

[0093] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles in an amount of at least 20% by mass of the particle collection, and ii) indirectly compressible (non-DC) sugar alcohol particles in an amount of at least 20% by mass of the particle collection.

[0094] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles in an amount of at least 25% by mass of the particle collection, and ii) indirectly compressible (non-DC) sugar alcohol particles in an amount of at least 25% by mass of the particle collection.

[0095] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles in an amount of at least 30% by mass of the particle collection, and ii) indirectly compressible (non-DC) sugar alcohol particles in an amount of at least 30% by mass of the particle collection.

[0096] In one embodiment of the present invention, the particle ensemble comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles in an amount of at least 10% by mass of the particle ensemble, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles in an amount of at least 10% by mass of the particle ensemble.

[0097] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles in an amount of at least 20% by mass of the particle collection, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles in an amount of at least 20% by mass of the particle collection.

[0098] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles in an amount of at least 25% by mass of the particle collection, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles in an amount of at least 25% by mass of the particle collection.

[0099] In one embodiment of the present invention, the particle collection comprises at least three types of sugar alcohol particles, including i) granulated sugar alcohol particles in an amount of at least 10% by mass of the particle collection, ii) indirectly compressible (non-DC) sugar alcohol particles in an amount of at least 10% by mass of the particle collection, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles in an amount of at least 10% by mass of the particle collection.

[0100] In one embodiment of the present invention, the particle collection comprises at least three types of sugar alcohol particles, including i) granulated sugar alcohol particles in an amount of at least 20% by mass of the particle collection, ii) indirectly compressible (non-DC) sugar alcohol particles in an amount of at least 20% by mass of the particle collection, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles in an amount of at least 20% by mass of the particle collection.

[0101] In one embodiment of the present invention, the particle collection comprises at least three types of sugar alcohol particles, including i) granulated sugar alcohol particles in an amount of at least 25% by mass of the particle collection, ii) indirectly compressible (non-DC) sugar alcohol particles in an amount of at least 25% by mass of the particle collection, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles in an amount of at least 25% by mass of the particle collection.

[0102] In one embodiment of the present invention, at least 80% by mass of the particle population has a particle size of less than 500 microns.

[0103] In one embodiment of the present invention, at least 95% by mass of the particle population has a particle size of less than 500 microns.

[0104] In one embodiment of the present invention, at least 80% by mass of the particle population has a particle size of less than 400 microns.

[0105] In one embodiment of the present invention, at least 95% by mass of the particle population has a particle size of less than 400 microns.

[0106] In one embodiment of the present invention, at least 80% by mass of the particle population has a particle size of less than 300 microns.

[0107] In one embodiment of the present invention, at least 95% by mass of the particle population has a particle size of less than 300 microns.

[0108] In one embodiment of the present invention, at least 30% by mass of the particle population has a particle size of less than 250 microns.

[0109] In one embodiment of the present invention, at least 50% by mass of the particle population has a particle size of less than 250 microns.

[0110] In one embodiment of the present invention, at least 60% by mass of the particle population has a particle size of less than 250 microns.

[0111] In one embodiment of the present invention, at least 20% by mass of the particle population has a particle size of less than 100 microns.

[0112] In one embodiment of the present invention, at least 30% by mass of the particle population has a particle size of less than 100 microns.

[0113] In one embodiment of the present invention, the particle population comprises at least 20% of one type of sugar alcohol particles having a particle size of less than 250 microns, and at least 20% of another type of sugar alcohol particles having a particle size of less than 250 microns, with more than 80% of the particles having a particle size of less than 250 microns.

[0114] In one embodiment of the present invention, the particle population comprises at least 20% of one type of sugar alcohol particles having a particle size of less than 250 microns, and at least 20% of another type of sugar alcohol particles having a particle size of less than 300 microns, with more than 80% of the particles having a particle size of less than 300 microns.

[0115] In one embodiment of the present invention, the particle population comprises at least 20% of one type of sugar alcohol particles having a particle size of less than 250 microns, and at least 20% of another type of sugar alcohol particles having a particle size of less than 100 microns, with more than 80% of the particles having a particle size of less than 100 microns.

[0116] In one embodiment of the present invention, the granulated sugar alcohol particles i) are either wet-granulated sugar alcohol particles or dry-granulated sugar alcohol particles.

[0117] In one embodiment of the present invention, the granulated sugar alcohol particles i) are dry-granulated sugar alcohol particles.

[0118] In one embodiment of the present invention, the granulated sugar alcohol particles i) include a binder such as a carboxymethylcellulose (CMC) binder. In alternative embodiments, the binder is gum arabic or maltodextrin. Suitable binders include gum arabic, methylcellulose, liquid glucose, tragacanth, ethylcellulose, gelatin, hydroxypropyl methylcellulose (HPMC), starch, hydroxypropylcellulose (HPC), pregelatinized starch, sodium carboxymethylcellulose (NaCMC), alginic acid, polyvinylpyrrolidone (PVP), maltodextrin (MD), cellulose, polyethylene glycol (PEG), polyvinyl alcohol, polymethacrylate, copovidone, or microcrystalline cellulose (MCC), either alone or in combination.

[0119] In one embodiment of the present invention, the granulated sugar alcohol particles i) include a wet binder such as water.

[0120] In one embodiment of the present invention, the granulated sugar alcohol particles i) are selected from granulated particles of xylitol, maltitol, isomalt, mannitol, erythritol, lactitol, dextrose, or combinations thereof.

[0121] In one embodiment of the present invention, the granulated sugar alcohol particles i) are selected from granulated particles of xylitol, maltitol, isomalt, mannitol, erythritol, lactitol, or combinations thereof.

[0122] In one embodiment of the present invention, the granulated sugar alcohol particles i) are selected from granulated particles of xylitol, maltitol, isomalt, mannitol, erythritol, or combinations thereof.

[0123] In one embodiment of the present invention, the granulated sugar alcohol particles i) are selected from granulated particles of xylitol, maltitol, isomalt, erythritol, or a combination thereof.

[0124] In one embodiment of the present invention, the granulated sugar alcohol particles i) are selected from granulated particles of xylitol, maltitol, isomalt, or a combination thereof.

[0125] In one embodiment of the present invention, the granulated sugar alcohol particles i) include granulated particles of maltitol.

[0126] In one embodiment of the present invention, the granulated sugar alcohol particles i) include granulated xylitol particles.

[0127] In one embodiment of the present invention, the granulated sugar alcohol particles i) are granulated xylitol particles.

[0128] In one embodiment of the present invention, the granulated sugar alcohol particles i) include granulated particles of dextrose.

[0129] In one embodiment of the present invention, more than 80% of the granulated sugar alcohol particles i) are in the range of 100 to 500 microns, for example, more than 50% are in the range of 100 to 400 microns. In one embodiment of the present invention, more than 80% of the granulated sugar alcohol particles i) are in the range of 100 to 500 microns. In one embodiment of the present invention, more than 80% of the granulated sugar alcohol particles i) are in the range of 100 to 400 microns. In one embodiment of the present invention, more than 80% of the granulated sugar alcohol particles i) are in the range of 200 to 500 microns. In one embodiment of the present invention, more than 80% of the granulated sugar alcohol particles i) are in the range of 200 to 400 microns.

[0130] In one embodiment of the present invention, granulated sugar alcohol particles i) impart free flow properties to the aggregate of particles.

[0131] In one embodiment of the present invention, granulated sugar alcohol particles i) impart free-flow properties to other types of sugar alcohol particles in a collection of particles.

[0132] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles ii) are selected from non-DC particles of xylitol, maltitol, isomalt, mannitol, erythritol, lactitol, or combinations thereof.

[0133] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles ii) are selected from non-DC particles of xylitol, maltitol, isomalt, mannitol, erythritol, or combinations thereof.

[0134] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles ii) are selected from non-DC particles of xylitol, isomalt, mannitol, erythritol, or combinations thereof.

[0135] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles ii) are selected from non-DC particles of mannitol, erythritol, or a combination thereof.

[0136] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles ii) include non-DC particles of mannitol.

[0137] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles ii) include non-DC particles of erythritol.

[0138] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles ii) are non-DC particles of erythritol.

[0139] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles provide a salivary secretion effect to the particle collection when the particle collection is administered orally.

[0140] In one embodiment of the present invention, the group of particles comprises at least two types of sugar alcohol particles, including i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, wherein the directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles contain sorbitol.

[0141] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, including i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, wherein the directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles are sorbitol.

[0142] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, wherein the directly compressible (DC) sugar alcohol particles iii) that are not granulated sugar alcohol particles include dextrose such as dextrose having an average particle size of less than 250 microns, for example less than 210 microns, for example less than 180 microns, for example less than 150 microns.

[0143] In some embodiments of the present invention, the ungranulated dextrose iii) has an average particle size of less than 250 microns. In some embodiments of the present invention, the ungranulated dextrose iii) has an average particle size of less than 210 microns. In some embodiments of the present invention, the ungranulated dextrose iii) has an average particle size of less than 180 microns. In some embodiments of the present invention, the ungranulated dextrose iii) has an average particle size of less than 150 microns.

[0144] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, wherein the directly compressible (DC) sugar alcohol particles iii) are dextrose such as dextrose having an average particle size of less than 250 microns, for example less than 210 microns, for example less than 180 microns, for example less than 150 microns.

[0145] Sorbitol is an example of a sugar alcohol that, when supplied as particles consisting of sorbitol, is considered DC grade, i.e., in its pure form. Ungranulated dextrose, for example, having an average particle size of less than 250 microns, less than 210 microns, less than 180 microns, or less than 150 microns, is another example of such a sugar alcohol that is considered DC grade, i.e., in its pure form. On the other hand, some other sugar alcohols are considered non-DC grade when supplied as particles consisting of a particular sugar alcohol. Therefore, such non-DC grade sugar alcohols are conventionally processed into DC grade sugar alcohols, for example, by granulating them using a binder.

[0146] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, wherein the directly compressible (DC) sugar alcohol particles iii) provide a cooling effect to the particle collection when the particle collection is administered orally.

[0147] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, wherein the directly compressible (DC) sugar alcohol particles iii) provide a cooling effect to the particle collection at the same level as or greater than xylitol based on mass percentage when the particle collection is administered orally.

[0148] In one embodiment of the present invention, the particle collection comprises at least three types of sugar alcohol particles, including i) granulated sugar alcohol particles, ii) indirectly compressible (non-DC) sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles ii) are non-DC particles of erythritol, and the directly compressible (DC) sugar alcohol particles iii) that are not granulated sugar alcohol particles are particles of sorbitol.

[0149] In one embodiment of the present invention, the particle collection comprises at least three types of sugar alcohol particles, including i) granulated sugar alcohol particles, ii) indirectly compressible (non-DC) sugar alcohol particles, and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, wherein the indirectly compressible (non-DC) sugar alcohol particles ii) are non-DC particles of erythritol, and the directly compressible (DC) sugar alcohol particles iii) that are not granulated sugar alcohol particles are dextrose particles, for example, dextrose particles with an average particle size of less than 250 microns, for example less than 210 microns, for example less than 180 microns, for example less than 150 microns.

[0150] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, in a mass ratio of i) to ii) between 0.2 and 5.

[0151] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, in a mass ratio of i) to ii) between 0.3 and 4.

[0152] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles, in a mass ratio of i) to ii) between 0.5 and 3.

[0153] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, in a mass ratio of i) to iii) between 0.2 and 5.

[0154] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, in a mass ratio of i) to iii) between 0.3 and 4.

[0155] In one embodiment of the present invention, the particle collection comprises at least two types of sugar alcohol particles, i) granulated sugar alcohol particles and iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles, in a mass ratio between i) and iii) between 0.5 and 3.

[0156] In one embodiment of the present invention, the active ingredient includes a pharmaceutical active ingredient.

[0157] In one embodiment of the present invention, the active ingredient includes an effective nutrient supplement or a nutritional supplement. In one embodiment of the present invention, the active ingredient includes zinc citrate.

[0158] In one embodiment of the present invention, the flow pack further comprises one or more flavoring agents.

[0159] In one embodiment of the present invention, the flow pack further comprises one or more high-intensity sweeteners. Preferred high-intensity sweeteners include, but are not limited to, sucralose, aspartame, salts of acesulfame, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, and stevioside (natural high-intensity sweeteners), either alone or in combination. To provide a longer-lasting sweetness and flavor perception, it may be desirable to encapsulate at least a portion of the artificial sweeteners or to control their release by other means. Desired release characteristics can be achieved using techniques such as wet granulation, wax granulation, spray drying, spray cooling, fluidized bed coating, preservation, encapsulation into yeast cells, and fiber extrusion. Encapsulation of sweeteners can also be achieved using other components such as resin compounds.

[0160] The level of use of high-intensity sweeteners varies considerably and depends on factors such as the potency and release rate of the sweetener, the desired sweetness of the product, the level and type of flavoring used, and cost considerations. Therefore, the effective level of high-intensity sweeteners may vary from about 0.001% to about 8% by mass (preferably about 0.02% to about 8% by mass). If a carrier used for encapsulation is included, the level of use of the encapsulated sweetener will be proportionally higher. Combinations of sugars and / or non-sugar sweeteners may be used in the formulation.

[0161] The amount of fragrance may be, for example, 0.1 to about 10% by mass of the formulation, or for example, 0.1 to about 6% by mass of the formulation.

[0162] Available flavorings include almond, almond amaretto, apple, bavarian cream, black cherry, black sesame seeds, blueberry, brown sugar, bubble gum, butterscotch, cappuccino, caramel, caramel cappuccino, cheesecake (graham crust), chili, cinnamon red hot, cotton candy, and circus cotton candy. Candy, clove, coconut, coffee, clear coffee, double chocolate, energy drink, ginger, glutamic acid, graham crackers, grape juice, green apple, Hawaiian punch, honey, Jamaican rum, Kentucky bourbon, kiwi, coolada, lemon, lemon-lime, tobacco, maple syrup, maraschino cherry, marshmallow, menthol, milk chocolate, mocha, Mountain Dew, peanut butter, pecan, peppermint, raspberry, banana, ripe banana, root beer, RY4, spearmint, strawberry, sweet cream, sweet tart, sweetener, toasted almonds, tobacco, tobacco blend, vanilla bean ice cream, vanilla cupcakes, Includes vanilla soft serve, vanillin, waffles, Belgian waffles, watermelon, whipped cream, white chocolate, wintergreen, amaretto, banana cream, black walnut, blackberry, butter, butter rum, cherry, chocolate hazelnut, cinnamon roll, cola, crème de menthe, eggnog, English toffee, guava, lemonade, licorice, maple, mint chocolate chip, orange cream, peach, piña colada, pineapple, plum, pomegranate, praline cream, red licorice, saltwater toffee, strawberry banana, strawberry kiwi, tropical punch, tutti frutti, vanilla, or any combination thereof.

[0163] In one embodiment of the present invention, the flavoring is a powdered flavoring.

[0164] In one embodiment of the present invention, the formulation further comprises at least one solubilizing agent selected from the group consisting of acacia, agar, alginic acid or its salts, carbomer, carboxymethylcellulose, carrageenan, cellulose, chitosan, copovidone, cyclodextrin, ethylcellulose, gelatin, guar gum, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, hypromellose, inulin, methylcellulose, pectin, polycarbophil or its salts, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, pullulan, starch, tragacanth, trehalose, xanthan gum, and mixtures thereof.

[0165] In one embodiment of the present invention, at least one solubilizing agent is selected from the group consisting of sodium alginate, polycarbophil calcium, xanthan gum, and mixtures thereof.

[0166] In one embodiment of the present invention, the formulation further comprises at least one viscosity agent that forms a gel having a positive surface charge when hydrated, and at least one viscosity agent that forms a gel having a negative surface charge when hydrated.

[0167] In one embodiment of the present invention, the flow pack further comprises a filler such as calcium carbonate and / or talc. In one embodiment of the present invention, the flow pack further comprises calcium carbonate. In one embodiment of the present invention, the flow pack further comprises talc.

[0168] In some embodiments of the present invention, the flow pack further comprises a flow accelerator. In some embodiments of the present invention, the flow pack further comprises silicon dioxide as a flow accelerator. In some embodiments of the present invention, the flow pack further comprises rice husks as a flow accelerator. In some embodiments of the present invention, the flow pack further comprises a cellulosic agent, such as Jelucel, as a flow accelerator. In some embodiments of the present invention, the flow accelerator is applied in an amount of less than 2.0% by mass of the powder mixture, for example, less than 1.5% by mass, for example, less than 1.0% by mass.

[0169] In one embodiment of the present invention, the particle collection includes gum-based particles. In one embodiment of the present invention, the particle collection includes chewing gum particles.

[0170] In one embodiment of the present invention, the flow pack includes an outer packaging material that encapsulates a collection of particles and one or more active ingredients.

[0171] In one embodiment of the present invention, the flow pack includes an aluminum outer casing that encapsulates a collection of particles and one or more active ingredients.

[0172] In one embodiment of the present invention, the flow pack includes an oxygen-impermeable outer packaging material that encapsulates a collection of particles and one or more active ingredients.

[0173] In one embodiment of the present invention, a collection of particles is administered directly into the mouth.

[0174] In one embodiment of the present invention, a collection of particles is poured into water, and the water is administered into the mouth.

[0175] In one embodiment of the present invention, the flow pack further includes a foaming system.

[0176] In one embodiment of the present invention, the flow pack further comprises a foaming system for a base and an acid. In one embodiment of the present invention, the flow pack further comprises a foaming system for a base and an organic acid. In one embodiment of the present invention, the flow pack further comprises a foaming system for a carbonate base and an organic acid.

[0177] In one embodiment of the present invention, the aggregate of particles is dry and fluid.

[0178] In one embodiment of the present invention, the particle collection provides an improved cooling effect compared to a powder mixture that does not contain at least one of the at least two types of sugar alcohol particles, and includes iii) directly compressible (DC) sugar alcohol particles that are not granulated sugar alcohol particles.

[0179] In one embodiment of the present invention, the particle collection yields an improved salivary effect compared to a powder mixture that does not contain at least one of at least two types of sugar alcohol particles, including non-directly compressible (non-DC) sugar alcohol particles.

[0180] In one embodiment of the present invention, the particle collection provides an improved mouthfeel compared to a powder mixture that does not contain at least one of at least two types of sugar alcohol particles.

[0181] In one embodiment of the present invention, the particle collection provides an improved mouthfeel compared to a powder mixture that does not contain at least one of at least two types of sugar alcohol particles, the improved mouthfeel including at least one of a less gritty mouthfeel, a less powdery mouthfeel, a less coarse mouthfeel, a less viscous mouthfeel, or an improved texture.

[0182] In one embodiment of the present invention, the particle cluster results in faster dissolution compared to a powder mixture that does not contain at least one of the at least two types of sugar alcohol particles.

[0183] In one embodiment of the present invention, the particle aggregate results in faster dissolution compared to a powder mixture that does not contain indirectly compressible (non-DC) sugar alcohol particles.

[0184] In one embodiment of the present invention, the particle aggregate results in faster dissolution compared to a powder mixture that does not contain directly compressible (DC) sugar alcohol particles, which are not granulated sugar alcohol particles.

[0185] In one embodiment of the present invention, the active ingredient comprises acetaminophen. In one embodiment of the present invention, the active ingredient comprises ibuprofen. In one embodiment of the present invention, the active ingredient comprises phenylephrine. In one embodiment of the present invention, the active ingredient comprises dextromethorphan. In one embodiment of the present invention, the active ingredient comprises guaifenesin. In one embodiment of the present invention, the active ingredient comprises diphenhydramine. In one embodiment of the present invention, the active ingredients comprises acetaminophen, phenylephrine, and dextromethorphan. In one embodiment of the present invention, the active ingredients comprises acetaminophen, phenylephrine, dextromethorphan, and guaifenesin.

[0186] In one embodiment of the present invention, the active ingredient is an oral care agent containing a zinc salt such as zinc acetate or zinc gluconate. In one embodiment of the present invention, the active ingredient is zinc acetate. In one embodiment of the present invention, the active ingredient is zinc gluconate. In one embodiment of the present invention, the active ingredient is zinc citrate.

[0187] In one embodiment of the present invention, the active ingredient comprises an oral care agent for oral care benefits including bad breath, plaque, gingivitis, whitening, or a combination of two or more thereof. In another embodiment of the present invention, the active ingredient comprises an oral care agent for oral care benefits comprising one or more probiotic agents.

[0188] In one embodiment of the present invention, the active ingredient includes a preservative. In one embodiment of the present invention, the active ingredient includes a preservative containing cetylpyridinium chloride (CPC). In one embodiment of the present invention, the active ingredient includes a preservative containing an essential oil. In one embodiment of the present invention, the active ingredient includes a preservative containing an essential oil selected from the group consisting of menthol, methyl salicylate, cineole, thymol, limonene, and any combination thereof. In one embodiment of the present invention, the essential oil contains menthol, methyl salicylate, cineole, and thymol.

[0189] In one embodiment of the present invention, the particle group has a dose of approximately 0.5 to 5.0 g. In one embodiment of the present invention, the particle group has a dose of approximately 0.5 to 4.0 g. In one embodiment of the present invention, the particle group has a dose of approximately 1.0 to 3.0 g. In one embodiment of the present invention, the particle group has a dose of approximately 1.0 to 2.0 g.

[0190] In one embodiment of the present invention, a collection of particles is at least partially dissolved in water, and the solution or dispersion is administered orally.

[0191] In one aspect of the present invention, a flow pack for oral delivery of an active ingredient is provided, comprising a particle cluster, a particle cluster and an outer packaging material for enclosing one or more active ingredients, wherein the particle cluster comprises at least two types of sugar alcohol particles, and at least one of the two types of sugar alcohol particles comprises i) granulated sugar alcohol particles. In this aspect, the flow pack may comprise a particle cluster, a particle cluster and an outer packaging material for enclosing one or more active ingredients according to an embodiment of the present invention.

[0192] In one aspect of the present invention, a flow pack is provided as a powder delivery system for improving saliva production. When the powder system is introduced into the mouth according to this aspect of the present invention, saliva can be produced to a greater extent than when using conventional types of sugar alcohol particles.

[0193] In one aspect of the present invention, a flow pack is provided as a powder delivery system for administering an active ingredient.

[0194] In one aspect of the present invention, a flow pack is provided as a powder delivery system for mouthwash.

[0195] In this aspect of the present invention, saliva is generated by a powder delivery system, and the user can forcibly circulate at least a portion of the generated saliva in the oral cavity by, for example, rinsing, washing, etc., thereby providing oral care benefits.

[0196] In one aspect of the present invention, a flow pack is provided as a powder delivery system for toothpaste. In this aspect of the present invention, the powder delivery system generates saliva, and the user can, for example, rinsing, washing, etc., force at least a portion of the generated saliva to circulate in the oral cavity, thereby providing the cleaning benefits of the toothpaste.

[0197] In one aspect of the present invention, a method for achieving oral care benefits, a) A step of preparing a flow pack containing a collection of particles according to any one of the preceding embodiments, wherein the powder delivery system is a collection of dry, flowable particles contained in the outer packaging material of the flow pack, b) A step of mimicking a liquid mouthwash by rinsing the aggregate of particles, thereby generating a fluid in the oral cavity without adding water. A method including this is provided.

[0198] In one aspect of the present invention, a method for achieving oral care benefits, a) A step of preparing a flow pack containing a collection of particles according to any one of the preceding embodiments, wherein the powder delivery system is a collection of dry, flowable particles contained in the outer packaging material of the flow pack, b) A step of subjecting a collection of particles to water to obtain a rinseable powder delivery system in which the particles are at least partially dissolved, and c) A step of rinsing a rinseable powder delivery system that is at least partially dissolved, thereby generating a fluid in the oral cavity. A method including this is provided. [Modes for carrying out the invention]

[0199] Accordingly, the present invention provides a flow pack for oral delivery of an active ingredient comprising a group of particles and one or more active ingredients, wherein the group of particles comprises at least two types of sugar alcohol particles, and at least one of the two types of sugar alcohol particles comprises i) granulated sugar alcohol particles (granulated sugar alcohol particles).

[0200] As used herein and in the claims, the verb “includes” and its conjugations are used in a non-restrictive sense, meaning that the item following the word is included, but not excluded, unless otherwise specifically mentioned. Furthermore, references to elements herein do not preclude the possibility of more than one element being present unless the context explicitly requires that only one element be present. Thus, nouns referring to elements generally mean “at least one.” Moreover, when used in this document in connection with the words “includes” or “contains,” nouns representing elements mean “one or more.” The expression “one or more” is intended to mean one, two, three or more.

[0201] As used herein, the numerical terms “approximately” or “about” are generally interpreted to include numbers that fall within the range of 5%, 10%, 15%, or 20% in either direction (greater than or less than) unless otherwise stated or the context makes it clear (except when such numbers are less than 0% or greater than 100% of a possible value).

[0202] As used herein, the terms "%" and "percent" refer to mass percentages unless otherwise specified.

[0203] In the context of this specification, the term "particle population" refers to a statistical population of particles. A particle population may be characterized by a number of different statistical parameters, such as particle distribution, mean particle size, and particle size distribution width. A particle population may have subpopulations, such as DC sugar alcohol particles and non-DC sugar alcohol particles.

[0204] The term "particle size" relates to the ability of particles to move through or be held by sieve holes of a particular size. As used herein, unless otherwise specified, the term "particle size" refers to the average particle size determined in accordance with European Pharmacopoeia 9.1 when using the particle size distribution estimation method 2.9.38 by analytical sieving.

[0205] The term "particle" or similar wording is intended to represent a single discrete composition of solid material, such as individual elements in granules or powder, having a specific size that may deviate considerably from the standard.

[0206] The powder systems provided in the present invention are generally provided as powders in which individual particles have not been further processed by a direct compression or compaction process, etc. Therefore, the powder systems are not in the form of tablets or similar aggregates of powder. However, some degree of particle aggregation of the present invention may occur to a minor extent either during storage of the powder system in a flow pack or during processing of the particles.

[0207] The term "flowpack" is intended to mean packaging containing a powder system according to the present invention, and packaging is generally given meaning in the field of flowpack technology. Generally, the powder system is applied while the packaging material is "flowing" in a machine that enables a high-speed and efficient process. Stick packs and sachets are examples of flowpacks.

[0208] The terms “powder system,” “powder delivery system,” or “formulation” are intended to be understood as the entire contents of the substance filled in the flow pack according to the present invention, excluding the packaging or packaging material surrounding the contents. Therefore, when referring to a “powder system,” “powder delivery system,” or “formulation,” it includes not only a “collection of particles” as a subdivision, but also one or more active ingredients, and may also include further components or particles.

[0209] As used herein, the term "dissolution" refers to the process by which particles enter a solvent (oral saliva) and produce a solution. Unless otherwise specified, dissolution means the complete dissolution of the compound. In some embodiments, the dissolution rate of the active ingredient is measured and shows improvement compared to conventional powder formulations.

[0210] The terms “in vivo release” or “in vivo release testing” or similar wording are intended to mean that the formulation is tested as outlined in the examples.

[0211] The terms “in vitro release” or “in vitro test of release” or similar wording are intended to mean that the formulation is tested according to the example, in particular in accordance with General Monograph 2.9.25 of the Fifth Edition of the European Pharmacopoeia.

[0212] In the context of this specification, the term “release” is intended to mean under “in vitro” conditions unless otherwise specified. In particular, “release rate” over a particular period is intended to mean the percentage amount of the active ingredient released during that period. In some embodiments, the process of releasing a substance corresponds to the dissolution of the substance in saliva.

[0213] The terms “sustained release” or “extended release” are intended in this specification to mean extended release over time. The terms “rapid release” or “rapid release” or “high release” are intended in this specification to mean a higher content released over a given period of time.

[0214] In the context of this specification, the term “become a liquid” is intended to mean that a collection of particles is suspended or dissolved in saliva and perceived as a liquid by the tester according to the test procedure for induced saliva production.

[0215] The term "delivery to the oral mucosa" or similar wording is intended to mean that the formulation will be tested according to the example.

[0216] As used herein, the terms “nutritional supplement,” “biologically active ingredient,” or simply “active ingredient” refer to substances that are biologically active and exert physiological effects on the human body for the benefit of the human body or any part thereof. Active ingredients include not only pharmaceutical active ingredients but also other active substances such as nutritional supplements, dietary aids, or oral care ingredients.

[0217] In the context of this specification, the term "suitable for medicinal active ingredients" refers to a formulation as a vehicle suitable for the inclusion and delivery of medicinal active ingredients, for example. However, it should be noted that powder systems may or may not contain medicinal active ingredients.

[0218] The terms “water-insoluble gum base,” “gum base,” “gum base matrix,” or similar wording primarily refer to water-insoluble and hydrophobic gum base components. “Gum base” may contain gum base polymers and plasticizers, waxes, emulsifiers, oils and / or fillers.

[0219] It should be noted that the term non-DC is readily understood within the scope of the technical field. Sugar alcohol suppliers provide clear guidance to users regarding their ability to be used in connection with tablet compression. Non-DC particles in this context refer to particles that are not explicitly recommended by the supplier for compression. Examples of non-DC grade erythritol include Zerose® Erythritol 16952F and Zerose Erythritol 16961 supplied by Cargill. Further examples of non-DC sugar alcohol particles include non-DC xylitol as Xivia C from Dupont, non-DC isomalt as Isomalt GS from Beneo Paltinit, and C from Cargill. *Examples of non-DC mannitol include Pharm Mannidex 16700 and non-DC maltitol as Maltisorb P200 from Roquette. An example of a directly compressible (DC) grade of erythritol is Zerose® DC 16966, also supplied by Cargill. Further examples of DC sugar alcohols include sorbitol particles, for example, Neosorb® P300DC from Roquette; mannitol particles, for example, Pearlitol® 300DC or Pearlitol 200 SD from Roquette; maltitol, for example, SweetPearl® P300DC; and xylitol, for example, Xylisorb® 200DC or Xylitab from Dupont.

[0220] Non-directly compressible (non-DC) sugar alcohols may include non-DC grade xylitol, non-DC grade erythritol, non-DC grade mannitol, non-DC grade maltitol, non-DC grade lactitol, non-DC grade isomalt, or non-DC grade of other suitable sugar alcohols.

[0221] Directly compressible (DC) sugar alcohols may include DC grades of sorbitol, xylitol, erythritol, mannitol, maltitol, lactitol, dextrose, isomalt, or other suitable sugar alcohols, which are essentially DC.

[0222] In embodiments of the present invention, the formulation comprises further components selected from the group consisting of flavorings, drying binders, anticaking agents, emulsifiers, antioxidants, enhancers, binders, absorption enhancers, high-intensity sweeteners, softeners, colorants, active ingredients, water-soluble indigestible polysaccharides, water-insoluble polysaccharides, or any combination thereof.

[0223] According to embodiments of the present invention, the emulsifier may be selected from the group consisting of sucrose esters of fatty acids (such as sucrose monostearate), polyethylene glycol esters or ethers (PEG) (such as caprylocaproyl macrogol-8 glyceride and lauroyl macrogol-32-glyceride), mono and diglycerides of fatty acids (such as glycerol monostearate, glycerol monolaurate, and glyceryl behenate), acetates of mono and diglycerides of fatty acids (Acetem), polyoxyethylene alkyl ethers, diacetyl tartrate of monoglycerides, lactylated monoglycerides, glycerophospholipids (such as lecithin), poloxamers (nonionic block copolymers of ethylene oxide and propylene oxide), cyclodextrin, and fatty acid esters of sorbitol (such as sorbitan monolaurate, sorbitan monostearate, sorbitan tristearate, and polysorbate).

[0224] According to embodiments of the present invention, the flavoring may be selected from the group consisting of coconut, coffee, chocolate, vanilla, grapefruit, orange, lime, menthol, licorice, caramel aroma, honey aroma, peanut, walnut, cashew, hazelnut, almond, pineapple, strawberry, raspberry, tropical fruit, cherry, cinnamon, peppermint, wintergreen, spearmint, eucalyptus and mint, apple, pear, peach, strawberry, apricot, raspberry, cherry, pineapple and plum essence, and other fruit essences. Examples of essential oils include peppermint, spearmint, menthol, eucalyptus, clove oil, bay oil, anise, thyme, cedar leaf oil, nutmeg, and the oils of the above fruits.

[0225] Suitable antioxidants for use include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), beta-carotene, tocopherol, acidulants such as vitamin C (ascorbic acid or its corresponding salt (ascorbate)), propyl gallate, catechin, green tea extract, and other synthetic and natural forms or mixtures thereof.

[0226] High-intensity sweeteners may also be used according to preferred embodiments of the present invention. Preferred high-intensity sweeteners include, but are not limited to, sucralose, aspartame, acesulfame salts, alitame, neotame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, monk fruit extract, advantame, stevioside, etc., either alone or in combination.

[0227] To achieve a longer-lasting sweetness and flavor perception, it may be desirable to encapsulate at least a portion of the high-intensity sweetener or to control its release by other means.

[0228] Desired release characteristics can be achieved using techniques such as wet granulation, wax granulation, spray drying, spray cooling, fluidized bed coating, preservation, encapsulation into yeast cells, and fiber extrusion. Encapsulation of sweeteners can also be achieved using other formulation components such as resin compounds.

[0229] The level of use of high-intensity sweeteners varies considerably and depends on factors such as the potency and release rate of the sweetener, the desired sweetness of the product, the level and type of flavoring used, and cost considerations. Therefore, the effective level of artificial sweeteners may vary from about 0.001% to about 8% by mass (preferably about 0.02% to about 8% by mass). If a carrier used for encapsulation is included, the level of use of encapsulated high-intensity sweeteners will be proportionally higher.

[0230] The present invention may optionally include one or more fillers / conditioners, such as magnesium carbonate and calcium, silicate compounds including sodium sulfate, crushed limestone, magnesium silicate and aluminum, kaolin and clay, aluminum oxide, silicon oxide, talc, titanium dioxide, monocalcium phosphate, dicalcium phosphate and tricalcium phosphate, cellulose polymers such as wood, and combinations thereof. According to embodiments of the present invention, one preferred filler / conditioner is calcium carbonate.

[0231] In one embodiment, the formulation according to the present invention includes a pharmaceutical, cosmetic, or biologically active substance. For example, a comprehensive list of such active substances can be found in International Publication No. 00 / 25598, incorporated herein by reference, and include drugs, nutritional supplements, preservatives, pH adjusters, smoking cessation agents, and substances for oral and dental care or treatment, such as compounds that can release hydrogen peroxide and urea during chewing. Examples of useful active substances in the form of preservatives include salts and derivatives of guanidine and biguanidine (e.g., chlorhexidine diacetate), and the following types of substances with limited water solubility: quaternary ammonium compounds (e.g., ceramine, chloroxylenol, crystal violet, chloramine), aldehydes (e.g., paraformaldehyde), derivatives of dequarin, polynoxylin, phenols (e.g., thymol, p-chlorophenol, cresol), hexachlorophene, salicylanilide compounds, triclosan, halogens (iodine, iodophores, chloroamines, dichlorocyanurates), alcohols (3,4-dichlorobenzyl alcohol, benzyl alcohol, phenoxyethanol, phenylethanol), Martindale, The Extra Pharmacopoeia, 28th edition. See also pages 547-578; this should include metal salts, complexes and compounds with limited water solubility, such as aluminum salts (e.g., potassium aluminum sulfate AlK(SO4)2, 12H2O), as well as salts, complexes and compounds of boron, barium, strontium, iron, calcium, zinc (zinc acetate, zinc chloride, zinc gluconate), copper (copper chloride, copper sulfate), lead, silver, magnesium, sodium, potassium, lithium, molybdenum, and vanadium; other compositions for oral and dental care: for example, fluorine-containing salts, complexes or compounds (sodium fluoride, sodium monofluorophosphate, amino fluoride, tin fluoride, etc.), phosphates, carbonates and selenium. Further effective substances can be found in J. Dent. Res, Vol.28, No.2, pp. 160-171, 1949.

[0232] Examples of active substances in the form of agents that adjust the pH of the oral cavity include acids, such as adipic acid, succinic acid, fumaric acid or salts thereof, or salts of citric acid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoric acid and glutaric acid, and acceptable bases, such as sodium, potassium, ammonium, magnesium or calcium, particularly magnesium and calcium carbonates, bicarbonates, phosphates, sulfates or oxides.

[0233] The active ingredients may include, but are not limited to, the following compounds or their derivatives: acetaminophen, acetylsalicylic acid, buprenorphine, bromhexine, cerucoxib, codeine, diphenhydramine, diclofenac, etoricoxib, ibuprofen, indomethacin, ketoprofen, lumiracoxib, morphine, naproxen, oxycodone, parecoxib, piroxicam, pseudoephedrine, rofecoxib, tenoxicam, tramadol, valdecoxib, calcium carbonate, and magaldrate. Disulfiram, bupropion, nicotine, azithromycin, clarithromycin, clotrimazole, erythromycin, tetracycline, granisetron, ondansetron, promethazine, tropisetron, brompheniramine, ceteridine, recoceteridine, chlorcyclidine, chlorpheniramine, chlorpheniramine, diphenhydramine, doxylamine, phenofenadine, guaifenesin, loratidine, desloratidine, phenyltroxamine, promethazine, pyridamine, terfenadine, troxertine, methyldopa, methyl Phenidate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, chlorhexidine, ecabet-sodium, haloperidol, allopurinol, cortinin, theophylline, propanolol, prednisolone, prednisone, fluoride, urea, Actot, glibenclamide, glipizide, metformin, miglitol, repaglinide, rosiglitazone, apomorphine, cialis, sildenafil, vardenafil, diphenoxylate, simethicone, cimetidine, famotidine, ranitidine, latinidine, cetoridine, lorata Zinc, aspirin, benzocaine, dextromethorphan, phenylpropanolamine, pseudoephedrine, cisapride, domperidone, metoclopramide, acyclovir, dioctyl sulfosuccinate, phenolphthalein, almotriptan, eletriptan, ergotamine, miguea, naratriptan, rizatriptan, sumatriptan, zolmitriptan, aluminum salt, calcium salt, ferro salt, silver salt, zinc salt, amphotericin B, chlorhexidine, miconazole, triamcinolone acetonide, melatonin, phenobarbitol,Caffeine, benzodiazepines, hydroxyzine, meprobamate, phenothiazine, buclidine, bromhetidine, cinnarizine, cyclizine, diphenhydramine, dimenhydrinate, buflomedil, amphetamine, caffeine, ephedrine, orlistat, phenylephedrine, phenylpropanolamine, pseudoephedrine, sibutramine, ketoconazole, nitroglycerin, nistatin, progesterone, testosterone, vitamin B12, vitamin C, vitamin A, vitamin D, vitamin E, green tea extract, pilocarpine, aluminum aminoacetate, cimetidine, esomeprazole, famotidine, lansoprazole, magnesium oxide, nizatide, and / or latinidine.

[0234] The present invention is suitable for increasing or promoting the release of activators selected from the group consisting of nutritional supplements, oral and dental compositions, preservatives, pH adjusters, smoking cessation agents, sweeteners, flavorings, fragrances, or drugs. Some of these are described below.

[0235] The activators used in connection with the present invention may be any substance that is desired to be released from the powder. Activators for which control and / or acceleration of the release rate is desired are substances with limited water solubility, typically less than 10 g / 100 mL, including substances that are completely water-insoluble. Examples include pharmaceuticals, nutritional supplements, oral compositions, smoking cessation agents, high-intensity sweeteners, pH adjusters, and flavorings.

[0236] Other active ingredients include, for example, paracetamol, benzocaine, cinnaridine, menthol, carvone, caffeine, chlorhexidine diacetate, cyclidine hydrochloride, 1,8-cineole, nandrolone, miconazole, mystatin, sodium fluoride, nicotine, cetylpyridinium chloride, other quaternary ammonium compounds, vitamin E, vitamin A, vitamin D, glibenclamide or its derivatives, progesterone, acetylsalicylic acid, dimenhydrinate, cyclidine, metronidazole, sodium bicarbonate, active ingredients from ginkgo biloba, active ingredients from propolis, active ingredients from Korean ginseng, methadone, peppermint oil, salicylamide, hydrocortisone, or astemizole.

[0237] Examples of activators in the form of nutritional supplements include, for example, vitamin B2 (riboflavin), B12, folic acid, folic acid, niacin, biotin, low soluble glycerophosphate, amino acids, nutritional salts and compounds of vitamins A, D, E and K, and minerals in the form of salts, complexes and compounds containing calcium, phosphorus, magnesium, iron, zinc, copper, iodine, manganese, chromium, selenium, molybdenum, potassium, sodium or cobalt.

[0238] Furthermore, a list of nutritions approved by authorities in different countries is referenced, for example, the U.S. Code of Federal Regulations, Title 21, Sections 182.5013.182 5997 and 182.8013-182.8997.

[0239] Examples of activators in the form of preservatives include, for example, salts and compounds of guanidine and biguanidine (e.g., chlorhexidine diacetate), and the following types of substances with limited water solubility: quaternary ammonium compounds (e.g., ceramine, chloroxylenol, crystal violet, chloramine), aldehydes (e.g., paraformaldehyde), dequarin compounds, polynoxylin, phenols (e.g., thymol, parachlorophenol, cresol), hexachlorophene, salicylate anilide compounds, triclosan, halogens (iodine, iodophores, chloroamines, dichlorocyanurates), alcohols (3,4-dichlorobenzyl alcohol, benzyl alcohol, phenoxyethanol, phenylethanol), and also Martindale, The Extra Pharmacopoeia, 28th edition. See pages 547-578; examples of metal salts, complexes and compounds with limited water solubility include, for example, aluminum salts (e.g., potassium aluminum sulfate AlK(SO4)2,12H2O), as well as salts, complexes and compounds of boron, barium, strontium, iron, calcium, zinc (zinc acetate, zinc chloride, zinc gluconate), copper (copper chloride, copper sulfate), lead, silver, magnesium, sodium, potassium, lithium, molybdenum, and vanadium; other compositions for oral and dental care include, for example, fluorine-containing salts, complexes and compounds (e.g., sodium fluoride, sodium monofluorophosphate, amino fluoride, tin fluoride), phosphates, carbonates and selenium.

[0240] Furthermore, see J. Dent. Res. Vol.28, No.2, pp. 160-171, 1949, which refers to a wide range of tested compounds.

[0241] Examples of activators in the form of agents that adjust the pH of the oral cavity include, for example: acceptable acids, such as adipic acid, succinic acid, fumaric acid, or salts thereof, or salts of citric acid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoric acid, and glutaric acid; and acceptable bases, such as sodium, potassium, ammonium, magnesium, or calcium, particularly magnesium and calcium carbonates, bicarbonates, phosphates, sulfates, or oxides.

[0242] Examples of active ingredients in the form of smoking cessation agents include, for example, nicotine, tobacco powder, or silver salts, such as silver acetate, silver carbonate, and silver nitrate.

[0243] Further examples of active agents are any type of medicine.

[0244] Examples of active pharmaceutical ingredients include caffeine, salicylic acid, salicylamide and related substances (acetylsalicylic acid, choline salicylate, magnesium salicylate, sodium salicylate), paracetamol, pentazocine salts (pentazocine hydrochloride and pentazocine lactate), buprenorphine hydrochloride, codeine hydrochloride and codeine phosphate, morphine and morphine salts (hydrochloride, sulfate, tartrate), methadone hydrochloride, ketobemidone and ketobemidone salts (hydrochloride), beta-blockers (propranolol), calcium channel blockers, verapamil hydrochloride, nifezimpine, and Pharm. Int., Nov. 85, pp. 267-271, Barney H. Hunter and Robert L. Suitable substances mentioned by Talbert and their salts include nitroglycerin, erythrityl tetranitrate, strychnine and its salts, lidocaine, tetracaine hydrochloride, etorphine hydrochloride, atropine, insulin, enzymes (e.g., papain, trypsin, amyloglucosidase, glucose oxidase, streptokinase, streptodolase, dextranase, alpha-amylase), polypeptides (oxytocin, gonadrelin, (LH,RH), desmopressin acetate (DDAVP), isoxuprine hydrochloride, ergotamine compounds, chloroquine (phosphate, sulfate), isosorbide, demoxitocin, heparin).

[0245] Other active ingredients include beta-lpeol, Letigen®, sildenafil citrate, and their derivatives.

[0246] Further examples of active ingredients include carbamide, CPP casein phosphopeptide; chlorhexidine, chlorhexidine diacetate, chlorhexidine chloride, chlorhexidine digluconate, hexetidine, strontium chloride, potassium chloride, sodium bicarbonate, sodium carbonate, fluorine-containing components, fluorides, sodium fluoride, and aluminum fluoride.

[0247] Further examples of active ingredients include ammonium fluoride, calcium fluoride, tin fluoride, other fluorine-containing compounds, ammonium fluorosilicate, potassium fluorosilicate, sodium fluorosilicate, ammonium monofluorolphosphate, calcium monofluorolphosphate, potassium monofluorolphosphate, sodium monofluorolphosphate, octadecentylammonium fluoride, and stearyltrihydroxyethylpropylenediamine dihydrofluoride.

[0248] Further examples of active ingredients include vitamins. These include vitamins A, B1, B2, B6, B12, folic acid, folic acid, niacin, pantothenic acid, biotin, C, D, E, and K. Minerals include calcium, phosphorus, magnesium, iron, zinc, copper, iodine, manganese, chromium, selenium, and molybdenum. Other active ingredients include Q10® and enzymes. Natural medicines include Ginkgo biloba, ginger, and fish oil.

[0249] Further examples of active ingredients include migraine medications, e.g., serotonin antagonists: sumatriptan, zolmitriptan, naratriptan, rizatriptan, eletriptan; nausea medications, e.g., cyclizine, cinnarizine, dimenhydramine, diphenhydrinato; hay fever medications, e.g., cetoridine, loratidine; pain relievers, e.g., buprenorphine, tramadol; oral disease medications, e.g., miconazole, amphotericin B, triamcinolonasetone; and drugs such as cisapride, domperidone, and metoclopramide. In preferred embodiments, the present invention relates to the release of nicotine and its salts.

[0250] In advantageous embodiments of the present invention, the active ingredients include acetylcysteine, ambroxol, amylmethacresol, benzocaine, bisacodyl, bismuth subsalicylate, bromhexine, cetirizine, cetylpyridinium, chlorhexidine, dextromethorphan hydrobromide, 2,4-dichlorobenzyl alcohol, doxylamine succinate, eucalyptus oil, flurbiprofen, glycerin, hexylresorcinol, lidocaine, menthol, myrrh, paracetamol, pectin, peppermint oil, phenol, phenylephrine, povidone-iodine, and psoi. Active ingredients for the throat selected from doephedrine, ranitidine, simethicone, sodium doxate, spearmint, zinc, or a combination thereof; alginic acid, atenolol, aspirin (acetylsalicylic acid), ampicillin, aminosalicylate, anhydrous citric acid, aspirin, bisacodyl, bismuth subsalicylate, bupropion, caffeine, calcium, calcium carbonate, cetirizine, cimetidine, cisapride, clarithromycin, desloratadine, dexlansoprazole, diphenhydramine HCl, diphenhydramine citrate, dimenhydrina Doxate, erythromycin, dopamine, esomeprazole, famotidine, fexofenadine HCl, guaifenesin, hydrotalcite, ibuprofen, ketoprofen, lactase enzyme, lansoprazole, loratadine, lorcaserin, loperamide, loperamide HCl, magnesium, magnesium carbonate, magnesium hydroxide, melatonin, metaamphetamine HCl, metoclopramide, metronidazole, montelukast, mycostatin, naltrexone, naproxen, naproxen sodium, nizatidine, omeprazole Ondansetron, orlistat, pantoprazole, paracetamol (acetaminophen), pectin, phentermine HCl, Polypodium leucotomos, prednisolone, prednisone, progesterone, propranolol, propantheline bromide, pseudoephedrine HCl, phentermine, rabeprazole, ranitidine, roflumilast, scopolamine butyl hydroxide, simethicone, sodium, sodium bicarbonate, sodium doxate, sumatriptan, testosterone, tetracycline, topiramate, vitamin A,The active ingredient for the gastrointestinal tract is selected from vitamin B, vitamin B12, vitamin C (ascorbic acid), vitamin D and vitamin E, vitamin K, or any combination thereof, and the active ingredient for buccal absorption is selected from atenolol, baclofen, caffeine, carvedilol, chlorpheniramine, chlorpheniramine maleate, fluticasone propionate, maleate, desmopressin, diltiazem hydrochloride, doxylamine succinate, mycostatin, nicotine, nifedipine, nitroglycerin, omeprazole, ondansetron, oxymetazoline HCl, oxytocin, phenylephrine, piroxicam, prednisone, propranolol, salbutamol sulfate, scopolamine butyl hydroxide, sumatriptan, triamcinolone acetonide, and any combination thereof.

[0251] The active ingredient may also be one or more cannabinoids selected from cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and tetrahydrocannabivaric acid (THCV A). More preferably, one or more cannabinoids are CBD or THC.

[0252] In one embodiment of the present invention, the formulation comprises particles containing a gum base, and the formulation is designed to be chewed and form a cohesive residue containing a water-insoluble component.

[0253] The application of gum in the context of this specification induces a delay in the release of the active ingredient, thereby promoting its absorption in the cheeks and upper throat when the pharmaceutical active ingredient is released from the formulation during chewing.

[0254] In one embodiment of the present invention, the formulation contains particles comprising a gum base, the gum base comprising at least 5% by mass of elastomer.

[0255] When a gum base is included in the formulation, sugar alcohols typically constitute about 5 to about 95% by mass, more typically about 20 to about 80% by mass, for example, 30 to 70% by mass, or 30 to 60% by mass of the formulation.

[0256] In one such embodiment of the present invention, the formulation further comprises, in addition to the sugar alcohols already described, materials selected from the group consisting of bulk sweeteners, flavorings, drying binders, anticaking agents, emulsifiers, antioxidants, enhancers, absorption enhancers, buffering agents, high-intensity sweeteners, softeners, colorants, or any combination thereof. [Examples]

[0257] (Example 1) <Procedure for particle size fractionation> Different sugar alcohols were fractionated according to their particle size by analyzing the particle size distribution of various raw materials. The analysis was performed using a Retsch AS 200 control sieve shaker equipped with a stack of 4-5 sieves. The mesh size was selected based on the raw material. The fractionation procedure was as follows: Sieves were stacked in a shaker in descending order of size, with the largest mesh size on top. Two small balls were added to each sieve with a mesh size of 250 μm or less to increase the distribution of fine particles on the sieve. 100 g of sugar alcohol sample was placed on top of the sieve stack, the lid was closed, and the shaker was started. The sample was shaken for 15 minutes at an amplitude of 1.5 mm. After the analysis was complete, the content of each sieve was determined to obtain the particle size distribution of the raw materials.

[0258] (Example 2) <Xylitol sugar alcohol particles> Different grades of xylitol were prepared and fractionated according to Example 1. Table 1 below shows the various xylitol particles to which the fractions were applied.

[0259] Granulated direct compressible (DC) xylitol was supplied by DuPont under the trade name Xylitab® 200. This product is commercially available, granulated using a wet granulation process with 2% sodium carboxymethylcellulose as a binder.

[0260] Crystalline indirect compressible (non-DC) xylitol was supplied by DuPont under the trade name Xivia C. This xylitol grade was ground to obtain a ground crystalline xylitol grade.

[0261] [Table 1]

[0262] (Example 3) <Maltitol sugar alcohol particles> We prepared maltitol particles with different particle size distributions. Table 2 below shows the various maltitol particles to which they were applied.

[0263] Granulated DC maltitol was supplied by Roquette under the trade name SweetPearl® P300 DC. This product is commercially available.

[0264] Crystalline non-DC maltitol was supplied by Roquette under the trade name SweetPearl® P200. This product is commercially available.

[0265] [Table 2]

[0266] (Example 4) <Isomalto sugar alcohol particles> Different grades of isomalt were prepared and fractionated according to Example 1. Table 3 below shows the various isomalt particles to which the fractions were applied.

[0267] Granulated DC isomalt was supplied by Beneo Palatinit under the trade name Isomalt DC 101. This product is commercially available.

[0268] Crystalline non-DC isomalt was supplied by Beneo Palatinit under the trade name Isomalt GS. This product is commercially available.

[0269] Granulated DC isomalt was supplied by Beneo Palatinit under the trade name galenIQ® 720. This product is commercially available.

[0270] [Table 3]

[0271] (Example 4A) <Dextrose particles> Granulated DC dextrose was supplied by Caldic under the trade name Royal-T® Dextrose with Maltodextrin 020510. This product is commercially available. Sieving analysis revealed a particle size distribution of up to 5.0% by mass of 1.19 mm (#16 mesh), up to 35.0% by mass of particles up to 177 microns (#80 mesh), and up to 25.0% by mass of particles up to 149 microns (#100 mesh). These particles are referred to as Sample 24A below. These particles exhibit good flow properties.

[0272] (Example 5) <Erythritol sugar alcohol particles> Erythritol particles with different particle size distributions were prepared and then combined with one or more additional sugar alcohol particles according to the present invention. Table 4 below shows the various erythritol particles to which they were applied.

[0273] The non-DC erythritol particles were provided by Cargill under the trade name Zerose (trademark) 16952. This product is a commercial product processed by the fermentation of carbohydrates. This grade was further fractionated according to Example 1.

[0274] The non-DC erythritol particles were provided by Jungbunzlauer under the trade name ERYLITE (registered trademark). This product is a commercial product processed by the fermentation of carbohydrates.

[0275] The non-DC erythritol particles were provided by Cargill under the trade name Zerose (trademark) 16961. This product is a commercial product processed by the fermentation of carbohydrates.

[0276]

Table 4

[0277] (Example 6) <Mannitol sugar alcohol particles> Mannitol was prepared and further combined with one or more additional sugar alcohol particles according to the present invention. Table 5 below shows the various mannitol particles applied.

[0278] The non-DC mannitol particles were provided by Cargill under the trade name C * Pharm Mannidex 16700. This product is a commercial product. This grade was further fractionated according to Example 1.

[0279]

Table 5

[0280] (Example 7) <Sorbitol sugar alcohol particles> Sorbitol having different particle size distributions was prepared and further combined with one or more additional sugar alcohol particles according to the present invention. Table 6 below shows the various sorbitol particles applied.

[0281] Sorbitol sugar alcohol particles are sold under the trade name C. * The product was supplied by Cargill's PharmSorbidex, under the label PharmSorbidex P16656. This is a commercially available product processed by sugar hydrogenation. This grade was further fractionated according to Example 1.

[0282] Sorbitol sugar alcohol particles are sold under the trade name C. * Provided by Cargill under the trademark Sorbidex (S 16607). This product is a commercially available product processed by sugar hydrogenation.

[0283] [Table 6]

[0284] (Example 7A) <Dextrose particles> Dextrose particles are sold under the trade name C * Provided by Cargill under Dex(trademark)02001. This product is commercially available. This grade was further fractionated according to Example 1.

[0285] [Table 7]

[0286] (Example 8) <Packaging for powder delivery systems> An appropriate amount of powder delivery system was weighed out (0.5-2g) and placed in a 1.0 inch x 2.5 inch foil bag with a tear-off notch. The foil bag was sealed by heat sealing to obtain individually packaged powder delivery systems.

[0287] (Example 9) <Combination of two types of sugar alcohol particles> Two types of sugar alcohol particles of various types from Examples 2 to 7 and 4A were mixed at a mass ratio of 1:1. The two types of sugar alcohol particles were mixed according to the following procedure: Accurately measured and equal amounts of each type of sugar alcohol particle were weighed (each 3 - 5 g). The two types of sugar alcohol particles were combined in a 70×100 mm plastic bag under ambient conditions, and the contents in the bag were thoroughly mixed. In this example, the granulated sugar alcohol particles from Examples 2 to 4 and 4A were combined with the non - directly compressible sugar alcohol particles from Examples 5 to 6.

[0288]

Table 8

[0289] (Example 9A) <Combination of two types of sugar alcohol particles> Two types of sugar alcohol particles of various types from Examples 2 to 7 and 4A were mixed at different mass ratios. The two types of sugar alcohol particles were mixed according to the following procedure: Accurate amounts of each type of sugar alcohol particle were weighed (each 3 - 5 g). The two types of sugar alcohol particles were combined in a 70×100 mm plastic bag under ambient conditions, and the contents in the bag were thoroughly mixed. The mass ratios between the granulated sugar alcohol particles from Examples 2 to 4 and 4A and the non - directly compressible sugar alcohol particles from Examples 5 to 6 were 0.1, 0.2, 0.5, 1, 3, 5, and 6, respectively.

[0290] (Example 9B) <Combination of two types of sugar alcohol particles> Two types of sugar alcohol particles of various types from Examples 2 to 7 were mixed at a mass ratio of 1:1. The two types of sugar alcohol particles were mixed according to the following procedure: Accurately measured and equal amounts of each type of sugar alcohol particle were weighed (each 3 - 5 g). The two types of sugar alcohol particles were combined in a 70×1'mm plastic bag under ambient conditions, and the contents in the bag were thoroughly mixed. In this example, the granulated sugar alcohol particles from Examples 2 to 4 were combined with the non - directly compressible sugar alcohol particles from Examples 5 to 6.

[0291]

Table 9

[0292] (Example 10) <Combination of two types of sugar alcohol particles> Various types of two sugar alcohol particles from Examples 2-7, 4A, and 7A were mixed in a 1:1 mass ratio. The two types of sugar alcohol particles were mixed according to the following procedure: the exact and equal amounts of each type of sugar alcohol particle were measured by mass (3-5 g each). The two types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. In this example, granulated sugar alcohol particles from Examples 2-4 and 4A were combined with sorbitol sugar alcohol particles from Example 7 or dextrose particles from Example 7A.

[0293] [Table 10]

[0294] (Example 10A) <Combination of two types of sugar alcohol particles> Various types of two sugar alcohol particles from Examples 2-7, 4A, and 7A were mixed in different mass ratios. The two types of sugar alcohol particles were mixed according to the following procedure: the exact amount of each type of sugar alcohol particle was measured by mass (3-5 g each). The two types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. The mass ratios between the granulated sugar alcohol particles from Examples 2-4 and 4A and the sorbitol sugar alcohol particles from Example 7 and the dextrose particles from Example 7A were 0.1, 0.2, 0.5, 1, 3, 5, and 6, respectively.

[0295] (Example 10B) <Combination of two types of sugar alcohol particles> Two types of sugar alcohol particles from various examples 2-7 were mixed in a 1:1 mass ratio. The two types of sugar alcohol particles were mixed according to the following procedure: the exact and equal amounts of each type of sugar alcohol particle were measured by mass (3-5 g each). The two types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. In this example, granulated sugar alcohol particles from examples 2-4 and sorbitol sugar alcohol particles from example 7 were combined.

[0296] [Table 11]

[0297] (Example 11) <Combination of 3 types of sugar alcohol particles> Three types of sugar alcohol particles from Examples 2-7, 4A, and 7A were mixed in a 1:1:1 mass ratio. The three types of sugar alcohol particles were mixed according to the following procedure: The exact and equal amounts of each type of sugar alcohol particle were measured by mass (3-5 g each). The three types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed.

[0298] [Table 12]

[0299] (Example 11A) <Combination of 3 types of sugar alcohol particles> Three types of sugar alcohol particles from Examples 2-7 were mixed in a 1:1:1 mass ratio. The three types of sugar alcohol particles were mixed according to the following procedure: The exact and equal amounts of each type of sugar alcohol particle were measured by mass (3-5 g each). The three types of sugar alcohol particles were placed in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed.

[0300] [Table 13]

[0301] (Example 11B) <Combination of 3 types of sugar alcohol particles> Two types of sugar alcohol particles from various examples 2-7 were mixed in different mass ratios. Three types of sugar alcohol particles were mixed according to the following procedure: The exact and equal amounts of each type of sugar alcohol particle were measured by mass (3-5 g each). The three types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed.

[0302] (Example 11C) <Combination of three types of sugar alcohol particles and a flow enhancer> The samples in Example 11 were tested with different flow enhancers. All samples were tested with a) 1% by mass of silicon dioxide and b) 2% by mass of silicon dioxide. In addition, all samples were tested with c) 2% by mass of rice husks provided by Ribus under the trade name Nu-Flow. These rice husks have a particle size of less than 74 microns.

[0303] (Example 12) <Combination of three types of sugar alcohol particles and further additives> Three types of sugar alcohol particles from Examples 2-7 were mixed in a 1:1:1 mass ratio. The three types of sugar alcohol particles were mixed according to the following procedure: the exact and equal amounts of each type of sugar alcohol particle were measured by mass (3-5 g each). The three types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. Further additives were included to enhance the sweetness profile and obtain different flavor profiles. This powder delivery system was placed in a flow pack according to Example 8.

[0304] [Table 14]

[0305] (Example 13) <Combination of three types of sugar alcohol particles and effervescent components> Three types of sugar alcohol particles from Examples 2-7 were mixed in a 1:1:1 mass ratio. The three types of sugar alcohol particles were mixed according to the following procedure: the exact and equal amounts of each type of sugar alcohol particle were measured by mass (3-5 g each). The three types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. Additional foaming agents were added to create a foaming sensation in the mouth. In addition, other active ingredients were added to some of the samples. This powder delivery system was placed in a flow pack according to Example 8.

[0306] [Table 15]

[0307] (Example 14) Three types of sugar alcohol particles from Examples 2-7 were mixed in a 1:1:1 mass ratio. The three types of sugar alcohol particles were mixed according to the following procedure: the exact and equal amounts of each type of sugar alcohol particle were measured by mass (3-5 g each). The three types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. Further immunoactive ingredients were added to obtain an immunoenhancing effect. The powder delivery system was placed in a flow pack according to Example 8.

[0308] [Table 16]

[0309] (Example 15) <Combination of three types of sugar alcohol particles and oral care active ingredients> Three types of sugar alcohol particles from Examples 2-7 were mixed in a 1:1:1 mass ratio. The three types of sugar alcohol particles were mixed according to the following procedure: the exact and equal amounts of each type of sugar alcohol particle were measured by mass (1-3 g each). The three types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. Further oral care active ingredients were added to achieve oral benefits such as caries prevention, remineralization, and plaque removal. This powder delivery system was placed in a flow pack according to Example 8.

[0310] [Table 17]

[0311] (Example 16) <Combination of three types of sugar alcohol particles and energy-activating components> Three types of sugar alcohol particles from Examples 2-7 were mixed in a 1:1:1 mass ratio. The three types of sugar alcohol particles were mixed according to the following procedure: the exact and equal amounts of each type of sugar alcohol particle were measured by mass (3-5 g each). The three types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. Furthermore, a pre-blended mixture of caffeine and vitamins B6, niacin, and B12 was added to obtain an invigorating effect. In addition, flavorings and HIS were added to enhance the sweetness profile and obtain different flavor profiles. This powder delivery system was placed in a flow pack according to Example 8.

[0312] [Table 18]

[0313] (Example 16A) <Combination of three types of sugar alcohol particles and different active ingredients> Three types of sugar alcohol particles from Examples 2-7 were mixed in a 1:1:1 mass ratio. The three types of sugar alcohol particles were mixed according to the following procedure: 500 mg of each type of sugar alcohol particle was measured by mass to obtain a total mass of 1500 mg. The three types of sugar alcohol particles were combined in a 70 × 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. This powder delivery system was placed in a flow pack according to Example 8.

[0314] [Table 19]

[0315] (Example 17) <Further sugar alcohol particles used as raw materials> The following raw material grades were used as examples to evaluate sensory benefits: Non-DC xylitol: Xivia C manufactured by DuPont. Ungranulated sorbitol - Cargill Co., Ltd. * PharmSorbidex P 16656 Ungranulated sorbitol - Cargill Co., Ltd. * Sorbidex(TM) S 16607 Non-DC isomalt: Isomalt GS manufactured by Beneo Paltinit. DC Mannitol: Pearlitol Flash manufactured by Roquette. Non-DC erythritol: Cargill Zerose 16952 DC Erythritol - Cargill Zerose 16966 DC Xylitol - Xylitab200 manufactured by DuPont. DC Isomalt - IsomaltDC 101 manufactured by Beneo Paltinit DC Mannitol - Pearlitol 250SD manufactured by Roquette DC Maltitol - Roquette Sweetpearl 300 DC DC Maltitol - Roquette Sweetpearl 200 DC DC Isomalt - manufactured by Beneo Paltinit, galenIQ® 720 Non-DC erythritol - ERYLITE® erythritol manufactured by Jungbunzlauer. Non-DC erythritol - Cargill's Zerose® 16961

[0316] (Example 18) <Active ingredients delivered to the oral mucosa> This study used a test panel of eight testers. Test subjects refrained from eating or drinking at least 30 minutes prior to the start of the test. Immediately before introducing the powder delivery system into the oral cavity, test subjects swallowed saliva. During the test, test subjects refrained from chewing and swallowing. After introducing the powder delivery system into the oral cavity, test subjects allowed the powder to dissolve for 10 seconds without moving it. Then, without chewing, they moved the saliva and the residue of the powder delivery system around in their mouths. One minute after the start of the test, the test subjects discarded the saliva containing part of the powder delivery system into a plastic cup and weighed it. The test was repeated under the same conditions as the one-minute test, but instead of discarding the saliva after one minute, the test subjects moved the saliva around and held it in their mouths for 3 minutes without swallowing. Then, the test subjects discarded the saliva containing part of the powder delivery system into a plastic cup and weighed it. The collected saliva samples were analyzed for the content of the active ingredient. Saliva was placed in a flask and weighed. Solvents were then added for dissolution and dilution. The solution was directly injected into an HPLC system and analyzed by an HPLC assay. Saliva was measured three times in triplicate for each of the eight test subjects, for a total of 24 measurements per sample. The average of the 24 measurements was calculated. By comparing the amount of released active ingredient (100%) with the amount of active ingredient in the saliva, the amount of active ingredient delivered to the oral mucosa could be estimated.

[0317] (Example 18A) <Hausner ratio of powder> In the following test example, the Hausner ratio was measured for the example blend. It is known to those skilled in the art that the Hausner ratio is the ratio of stamped powder (g / mL) to unstamped powder (g / mL) by known methods. The ratio represents the ratio between the bulk densities of stamped powder and unstamped powder. The Hausner ratio is generally classified by its compressibility index and represents the fluidity of the powder. The best fluidity is obtained when the Hausner ratio is 1.00, and the higher the Hausner ratio, the lower the fluidity of the powder.

[0318] Three types of sugar alcohol particles from Examples 2-7 were mixed in a 1:1 or 1:1:1 mass ratio. The three types of sugar alcohol particles were mixed according to the following procedure: an accurate and equal amount of each type of sugar alcohol particle was measured by mass (3-5 g each). The three types of sugar alcohol particles were combined in a 70 x 100 mm plastic bag under ambient conditions, and the contents of the bag were thoroughly mixed. This powder delivery system was placed in a flow pack according to Example 8.

[0319] [Table 20]

[0320] (Example 19) <Sensory Evaluation Test Structure> Sensory tests were performed on all examples to clarify the most important features and properties of the powder delivery systems. These sensory parameters are important indicators of the structure of the powder delivery system compositions. The structure is a fundamental guide to how the powder delivery systems resemble the structure of a comparative powder delivery system used as a baseline in the test series; that is, the powder delivery systems are compared with each other in a test series of preferably five samples. The test configuration consisted of eight testers in the test panel. Each tester was a healthy individual objectively appointed according to the prescribed requirements. Sensory analysis was performed in accordance with ISO 4121-2003 and under the test conditions of ISO 8589. The results are the average of the results of the eight testers.

[0321] Testers assigned scores from "+" to "+++++", where "+" indicated poor performance compared to the reference sample, and "+++++" indicated excellent performance. The reference sample was given a score of "++" for all parameters, meaning that "+++++" meant the powder delivery system was far better than the reference, and "+" meant the powder delivery system was inferior to the reference. "0" indicated that the sample was not tested.

[0322] The following six different parameters were tested on the test panel.

[0323] [Table 21]

[0324] "Mouthfeel" - The overall impression of the powder delivery system when placed in the mouth, relating to elements such as roughness, texture, and a gritty or powdery feel.

[0325] "Mouth-melting" - The impression of the powder delivery system when placed in the mouth. For example, if the powder delivery system felt like it was dissolving on the tongue and resulted in a sticky feeling, it would receive a low score, while an experience with less stickiness would receive a higher score. Powder delivery systems that dissolved slowly would receive a low score, while those that dissolved quickly would receive a high score.

[0326] "Flavor" - The overall impression of the powder delivery system regarding flavor, including the sweetness profile. For example, very little flavor experience resulted in a very low score, and too much flavor also resulted in a very low score.

[0327] "Off-note" - The overall impression of off-notes caused by the active ingredients in the composition. For example, a low score was given if off-notes (grassy, ​​bitter, throat irritation) were experienced in the throat, and a low score was also given if any other unpleasant sensations were experienced.

[0328] "Saliva secretion" - The overall impression of the salivary effect.

[0329] "Cooling" - The overall impression of the cooling.

[0330] (Example 20) <Sensory evaluation of sensory parameters>

[0331] [Table 22]

[0332] The results for the above samples correspond to examples of selected samples tested for sensory evaluation using the configuration of Example 19. Further samples provided in the previous example were similarly tested for the same parameters, and the results were considered similarly favorable.

[0333] (Example 21) <Evaluation of sensory experience>

[0334] [Table 23]

[0335] The results for the samples described above correspond to examples of selected samples tested for sensory experience. Further samples provided in the previous examples were similarly tested for mouthfeel and sensory experience, and the results were considered equally favorable.

Claims

1. A flow pack for oral delivery of an active ingredient, wherein the flow pack comprises an outer packaging material that encloses a powder delivery system containing a collection of particles and one or more active ingredients, which can be dissolved in oral fluid after oral administration. The particle collection comprises at least two types of sugar alcohol particles having different particle size distributions, all of which are free-flowing. At least one of the at least two types of sugar alcohol particles comprises i) granulated sugar alcohol particles, and at least one of the at least two types of sugar alcohol particles, other than i) granulated sugar alcohol particles, comprises ii) indirectly compressible (non-DC) sugar alcohol particles, A flow pack in which a collection of particles is dry, flowable, and characterized by a Hausner ratio between 1.00 and 1.

59.

2. The flow pack according to claim 1, wherein the at least two sugar alcohol particles further comprise iii) ungranulated direct compressible (DC) sugar alcohol particles.

3. The flow pack according to claim 1 or 2, wherein the ii) non-directly compressible (non-DC) sugar alcohol particles have a particle size in which more than 80% of the particles are less than 500 microns.

4. The flow pack according to any one of claims 1 to 3, wherein the at least two sugar alcohol particles further comprise iii) ungranulated direct compressible (DC) sugar alcohol particles having a particle size in which more than 80% of the particles are less than 500 microns.

5. The flow pack according to any one of claims 1 to 4, wherein the at least two sugar alcohol particles further comprise iii) ungranulated direct compressible (DC) sugar alcohol particles having a particle size in which more than 95% of the particles are less than 500 microns.

6. The flow pack according to any one of claims 1 to 5, wherein the ii) non-directly compressible (non-DC) sugar alcohol particles have a particle size of less than 250 microns for more than 80% thereof, and the iii) ungranulated directly compressible (DC) sugar alcohol particles have a particle size of less than 300 microns for more than 80% thereof.

7. The flow pack according to any one of claims 1 to 6, wherein the i) granulated sugar alcohol particles are present in an amount of at least 20% by mass of the particle population.

8. The flow pack according to any one of claims 1 to 7, wherein i) granulated sugar alcohol particles are present in an amount of at least 20% by mass of the particle population, and ii) indirectly compressible (non-DC) sugar alcohol particles are present in an amount of at least 20% by mass of the particle population.

9. The flow pack according to any one of claims 1 to 8, wherein i) granulated sugar alcohol particles are present in an amount of at least 20% by mass of the particle population, and the particle population further comprises iii) ungranulated directly compressible (DC) sugar alcohol particles in an amount of at least 20% by mass of the particle population.

10. The flow pack according to any one of claims 1 to 9, wherein the granulated sugar alcohol particles i) are selected from granulated particles of xylitol, maltitol, isomalt, mannitol, erythritol, lactitol, dextrose, or combinations thereof.

11. The flow pack according to any one of claims 1 to 10, wherein the non-directly compressible (non-DC) sugar alcohol particles ii) are selected from non-DC particles of xylitol, maltitol, isomalt, mannitol, erythritol, lactitol, or combinations thereof.

12. The flow pack according to any one of claims 1 to 11, wherein the non-directly compressible (non-DC) sugar alcohol particles ii) are selected from non-DC particles of xylitol, maltitol, isomalt, mannitol, erythritol, or combinations thereof.

13. The flow pack according to any one of claims 1 to 12, wherein the at least two sugar alcohol particles further comprise iii) ungranulated direct compressible (DC) sugar alcohol particles, and the iii) ungranulated direct compressible (DC) sugar alcohol particles comprise sorbitol and / or dextrose.

14. The flow pack according to any one of claims 1 to 13, wherein the mass ratio of i) granulated sugar alcohol particles and ii) indirectly compressible (non-DC) sugar alcohol particles is between 0.2 and 5.

15. The flow pack according to any one of claims 1 to 14, wherein the active ingredient is selected from the group consisting of acetaminophen, ibuprofen, phenylephrine, dextromethorphan, guaifenesin, diphenhydramine, and combinations thereof.

16. The flow pack according to any one of claims 1 to 15, wherein the active ingredient comprises one or more of zinc acetate, zinc gluconate, and zinc citrate.

17. The Flowpack according to any one of claims 1 to 16, wherein the active ingredient comprises an oral care agent for oral care benefits including bad breath, plaque, gingivitis, whitening, or a combination of two or more thereof.

18. The flow pack according to any one of claims 1 to 17, wherein the active ingredient comprises a preservative containing cetylpyridinium chloride (CPC).

19. The flow pack according to any one of claims 1 to 18, wherein the active ingredient comprises an essential oil selected from the group consisting of menthol, methyl salicylate, cineole, thymol, limonene, and any combination thereof.

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