WO2025221880A1

WO2025221880A1 - Free-flowing, water-soluble dentifrice granules and methods for producing the same

Info

Publication number: WO2025221880A1
Application number: PCT/US2025/024954
Authority: WO
Inventors: Yanyan Guo; Michael Popplewell; Salvatore Alber CELESTE; Adam TOTH
Original assignee: International Flavors and Fragrances Inc; Additive Advantage LLC
Current assignee: International Flavors and Fragrances Inc; Additive Advantage LLC
Priority date: 2024-04-16
Filing date: 2025-04-16
Publication date: 2025-10-23
Anticipated expiration: 2026-10-16

Abstract

Disclosed are free-flowing, water-soluble dentifrice granules which are printed and dried to have a uniform size, weight and density, and fast dissolution time.

Description

TITLE

FREE-FLOWING, WATER-SOLUBLE DENTIFRICE GRANULES AND METHODS FOR PRODUCING THE SAME

TECHNICAL FIELD

[0001] The present invention relates to free-flowing, water-soluble dentifrice granules.

More specifically, the instant disclosure provides methods and compositions concerning free-flowing, water-soluble dentifrice granules having a porosity of 10 to 70%.

BACKGROUND

[0002] Dentifrices such as mouthwashes and mouth rinses are routinely used by consumers as part of their oral care hygiene regimens. It is well known that dentifrices can provide both therapeutic and cosmetic hygiene benefits to consumers. For example, therapeutic benefits include caries prevention, which is typically delivered through the use of various fluoride salts; gingivitis prevention by the use of antimicrobial agents such as triclosan, stannous fluoride, or essential oils; or hypersensitivity control through the use of ingredients such as strontium chloride or potassium nitrate. Cosmetic benefits provided by dentifrices include control of plaque and calculus formation, removal and prevention of tooth stain, tooth whitening, breath freshening, and overall improvements in mouth feel impression.

[0003] Dentifrices are typically provided as aqueous solutions in bottles or containers, which are often large, and costly to store and ship. Moreover, large bottles of mouthwash are inconvenient for travelers. Dry dentifrice granules have been offered to overcome some of these problems, but such granules are not readily soluble. Effervescent agents have been included in the dry granules to aid solubility, but such agents can negatively interact with components of the dentifrice and tend to make the granules hygroscopic, dramatically shortening the life of the product.

[0004] There is a continuing need for dentifrice granules which are readily soluble but do not require the use of effervescent agents. SUMMARY OF THE INVENTION

[0005] In an aspect of the present invention, a free-flowing, water-soluble dentifrice granule is presented having a flavor agent, a dentifrice active and an emulsifier, wherein said granule has a porosity of from about 10% to about 70%.

Optionally, the flavor agent is menthol, thymol, eucalyptol, methyl salicylate, wintergreen oil, myrrh oil, fennel oil, tea tree oil, peppermint oil, lemon oil, spearmint oil, mint flavor, vanilla flavor, cinnamon flavor, berry flavor (optionally strawberry, raspberry or blueberry), orange flavor, mango flavor, cherry flavor, bubblegum flavor, chocolate flavor or a combination thereof.

[0006] Optionally, the flavor agent is peppermint oil. Optionally, the dentifrice granule has flavor retention of more than 75%.

[0007] Optionally, the dentifrice active is a fluoride, an essential oil, triclosan, cetylpyridinium chloride, a hydrogen peroxide source, an enzyme, chlorhexidine, strontium chloride, potassium nitrate or a vitamin. Optionally, the dentifrice active is an essential oil. Optionally, the essential oil is menthol, eucalyptol, methyl salicylate, myrrh oil, fennel oil, tea tree oil or thymol.

[0008] Optionally, the dentifrice active is a fluoride. Optionally, the fluoride is amine fluoride, silver diamine fluoride, sodium monofluorophosphate, stannous fluoride or sodium monofluorophosphate.

[0009] Optionally, the dentifrice active is a hydrogen peroxide source. Optionally, hydrogen peroxide source is carbamide peroxide, sodium percarbonate, calcium peroxide, peroxydone or perbenzoic acid.

[0010] Optionally, the emulsifier is lecithin, monoglyceride, diglyceride, sodium stearoyl lactylate, celluloses, starches or modified starches, gums, sucrose esters, sucroglycerides, polyglycerol esters, polyglycerol polyricinoleate, sorbitan esters, pectin, proteins or combinations thereof.

[0011] Optionally, the porosity is about 10% to about 70%. Optionally, the porosity is about 30% to about 60%.

[0012] Optionally, the granule also has a disintegrant. Optionally, the disintegrant is an enzyme (such as amylase, protease, cellulase, or invertase), starch and/or starch derivatives (such as sodium starch glycolate), cellulose and/or cellulose derivatives (such as croscarmellose sodium, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and microcrystalline cellulose), a hydrophilic colloidal substance (such as alginate, alginic acid NF), natural gums (such as guar gum, xantham gum, locust bean gum), crosslinked polyvinylpyrrolidone, soy polysaccharides or combinations thereof.

[0013] Optionally, the granule also has a surfactant. Optionally, the surfactant is sodium lauryl sulfate, polysorbate, poloxamers, sodium coconut monoglycerides sulfonate, glycerol fatty acid ester, propylene glycol fatty acid ester, polyethylene glycol (PEG), sorbitan fatty acid ester, sucrose ester, taurine, sarcosine, or combinations thereof.

[0014] Optionally, the granule also has an effervescent agent. Optionally, the effervescent agent is a bicarbonate salt or carbonate salt such as sodium carbonate, sodium bicarbonate, sodium percarbonate, potassium carbonate, potassium bicarbonate or a combination thereof.

[0015] Optionally, the granule also has an effervescent activator. Optionally, the effervescent activator is citric acid, ascorbic acid, malic acid, fumaric acid, tartaric acid, succinic acid, adipic acid, pyruvic acid, oxaloacetic acid, maleic acid, alpha-ketoglutaric acid, alginic acid, amino acids, aconitic acid, lactic acid, and acid salt such as monosodium citrate, disodium citrate, or a combination thereof.

[0016] Optionally, the granule dissolves in water at 23°C ± 1.0°C in less than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 minute.

[0017] In another aspect of the present invention, a method is presented for producing a free-flowing, water-soluble dentifrice granule having a porosity of from about 10% to about 70%, the method having the steps of:

[0018] (a) dispensing discrete droplets of a slurry having a flavor agent, a dentifrice active and an emulsifier onto a non-stick surface;

[0019] (b) drying the dispensed droplets of (a) to produce the free- flowing, water- soluble dentifrice granule having the porosity of from about 10% to about 70%.

[0020] Optionally the flavor agent is menthol, thymol, eucalyptol, methyl salicylate, wintergreen oil, myrrh oil, fennel oil, tea tree oil, peppermint oil, lemon oil, spearmint oil, mint flavor, vanilla flavor, cinnamon flavor, berry flavor (optionally strawberry, raspberry or blueberry), orange flavor, mango flavor, cherry flavor, bubblegum flavor, chocolate flavor or a combination thereof.

[0021] Optionally, the flavor agent is peppermint oil. Optionally, the dentifrice granule has flavor retention of more than 75%. [0022] Optionally, the dentifrice active is a fluoride, an essential oil, triclosan, cetylpyridinium chloride, a hydrogen peroxide source, an enzyme, chlorhexidine, strontium chloride, potassium nitrate or a vitamin. Optionally, the dentifrice active is an essential oil. Optionally, the essential oil is menthol, eucalyptol, methyl salicylate, myrrh oil, fennel oil, tea tree oil or thymol.

[0023] Optionally, the dentifrice active is a fluoride. Optionally, the fluoride is amine fluoride, silver diamine fluoride, sodium monofluorophosphate, stannous fluoride or sodium monofluorophosphate.

[0024] Optionally, the dentifrice active is a hydrogen peroxide source. Optionally, hydrogen peroxide source is carbamide peroxide, sodium percarbonate, calcium peroxide, peroxydone or perbenzoic acid.

[0025] Optionally, the emulsifier is lecithin, monoglyceride, diglyceride, sodium stearoyl lactylate, celluloses, starches or modified starches, gums, sucrose esters, sucroglycerides, polyglycerol esters, polyglycerol polyricinoleate, sorbitan esters, pectin, proteins or combinations thereof.

[0026] Optionally, the porosity is about 10% to about 70%. Optionally, the porosity is about 30% to about 60%.

[0027] Optionally, the granule also has a disintegrant. Optionally, the disintegrant is an enzyme (such as amylase, protease, cellulase, or invertase), starch and/or starch derivatives (such as sodium starch glycolate), cellulose and/or cellulose derivatives (such as croscarmellose sodium, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and microcrystalline cellulose), a hydrophilic colloidal substance (such as alginate, alginic acid NF), natural gums (such as guar gum, xantham gum, locust bean gum), crosslinked polyvinylpyrrolidone, soy polysaccharides or combinations thereof.

[0028] Optionally, the granule also has a surfactant. Optionally, the surfactant is sodium lauryl sulfate, polysorbate, poloxamers, sodium coconut monoglycerides sulfonate, glycerol fatty acid ester, propylene glycol fatty acid ester, polyethylene glycol (PEG), sorbitan fatty acid ester, sucrose ester, taurine, sarcosine, or combinations thereof.

[0029] Optionally, the granule also has an effervescent agent. Optionally, the effervescent agent is a bicarbonate salt or carbonate salt such as sodium carbonate, sodium bicarbonate, sodium percarbonate, potassium carbonate, potassium bicarbonate or a combination thereof. [0030] Optionally, the granule also has an effervescent activator. Optionally, the effervescent activator is citric acid, ascorbic acid, malic acid, fumaric acid, tartaric acid, succinic acid, adipic acid, pyruvic acid, oxaloacetic acid, maleic acid, alpha-ketoglutaric acid, alginic acid, amino acids, aconitic acid, lactic acid, and acid salt such as monosodium citrate, disodium citrate, or a combination thereof.

[0031] Optionally, the granule dissolves in water at 23°C ± 1.0°C in less than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 minute.

[0032] Optionally, in a granule presented in accordance with the instant invention, the dentifrice active is one or more of an anticavity agent, an antimicrobial, an antiseptic agent, a tooth whitening agent, a tooth desensitizing agent, a disclosing agent, dental preventative or aesthetic enhancers.

[0033] Optionally, the dentifrice active is an anticavity agent. Optionally, the anticavity agent is a fluoride, a xylitol or a remineralizer. Optionally, the anticavity agent is a remineralizer. Optionally, the remineralizer is hydroxyapatite, silver nanoparticles, calcium phosphate, casein phosphopeptide-amorphous calcium phosphate, calcium glycerophosphate, or other dentifrice designed to rehabilitate dentin or enamel.

[0034] Optionally, the dentifrice active is an antimicrobial agent. Optionally, the antimicrobial agent is triclosan, an essential oil, cetylpyridinium chloride, chlorhexidine, chlorine dioxide, or aloe vera.

[0035] Optionally, the dentifrice active is one or more enzymes. Optionally, the one or more enzymes are papain, bromelain, tannase, or glucose oxidase.

[0036] Optionally, the dentifrice active is a tooth desensitizing agent. Optionally, the tooth desensitizing agent is potassium nitrate, strontium chloride, strontium acetate, baking soda, fluorides, bonding resins, oxalate, arginine, casein phosphopeptide-amorphous calcium phosphate, calcium phosphate, calcium carbonate, gluma, or vitamins.

[0037] Optionally, the dentifrice active is a dental preventative. Optionally, the dental preventative is an anti-gingivitis, anti-plaque, anti-fungal agents.

[0038] Optionally, in a method presented in accordance with the instant invention, the dentifrice active is one or more of an anticavity agent, an antimicrobial, an antiseptic agent, a tooth whitening agent, a tooth desensitizing agent, a disclosing agent, dental preventative or aesthetic enhancers. [0039] Optionally, the dentifrice active is an anticavity agent. Optionally, the anticavity agent is a fluoride, a xylitol or a remineralizer. Optionally, the anticavity agent is a remineralizer. Optionally, the remineralizer is hydroxyapatite, silver nanoparticles, calcium phosphate, casein phosphopeptide-amorphous calcium phosphate, calcium glycerophosphate, or other dentifrice designed to rehabilitate dentin or enamel.

[0040] Optionally, the dentifrice active is an antimicrobial agent. Optionally, the antimicrobial agent is triclosan, an essential oil, cetylpyridinium chloride, chlorhexidine, chlorine dioxide, or aloe vera.

[0041] Optionally, the dentifrice active is one or more enzymes. Optionally, the one or more enzymes are papain, bromelain, tannase, or glucose oxidase.

[0042] Optionally, the dentifrice active is a tooth desensitizing agent. Optionally, the tooth desensitizing agent is potassium nitrate, strontium chloride, strontium acetate, baking soda, fluorides, bonding resins, oxalate, arginine, casein phosphopeptide-amorphous calcium phosphate, calcium phosphate, calcium carbonate, gluma, or vitamins.

[0043] Optionally, the dentifrice active is a dental preventative. Optionally, the dental preventative is an anti-gingivitis, anti-plaque, anti-fungal agents.

[0044] Optionally, in a granule presented in accordance with the present invention, porosity is controlled by formulation parameters and processing conditions.

[0045] Optionally, in a granule presented in accordance with the present invention, wherein the porosity in the range of about 30% to about 60%, the granule exhibits an improved dissolution rate and favorable friability characteristics.

DETAILED DESCRIPTION OF THE INVENTION

[0046] All parts, percentages and proportions referred to herein and in the claims are by weight unless otherwise indicated.

[0047] The values and dimensions disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Instead, unless otherwise specified, each such value is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a value disclosed as “50%” is intended to mean “about 50%. ”

[0048] The terms “capsule” and “microcapsule” are used interchangeably. [0049] The terms “g,” “mg,” and “pg” refer to “gram,” “milligram,” and “microgram,” respectively. The terms “L” and “mL” refer to “liter” and “milliliter,” respectively.

[0050] The details of one or more aspects of the invention are set forth in the description below. Other features, objects, and advantages will be apparent from the description and the claims.

[0051] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.

[0052] Before the exemplary embodiments are described in more detail, it is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, exemplary methods, and materials are now described.

[0053] As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a gene” includes a plurality of such candidate agents and reference to “the cell” includes reference to one or more cells and equivalents thereof known to those skilled in the art, and so forth.

[0054] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior invention.

[0055] In an aspect of the present invention, granules are provided having a defined porosity. It has been discovered, in accordance with the present invention, that more porous granules are more easily dissolved in a solvent than less porous granules. Granules of the instant invention may be used in a wide variety of setting including but not limited to dentifrice granules, flavor granules, fragrance/scent granules, nutraceutical/pharmaceutical granules (such as vitamins, minerals, OTC antibiotics, especially for the applications involving two-part activation), enzyme granules (such as protease), homecare (such as detergent, hand soap, body wash, shampoo), agriculture (such as fertilizer) and pesticide/insecticide/repellent granules, antioxidant/scavenger/emitter, topical preparation.

[0056] In an aspect of the present invention, dentifrice granules and a dentifrice granule system are provided for delivering a dentifrice active, wherein the dentifrice granules may be printed and dried to have a uniform size, weight and density, and a short dissolution time (e.g. less than 10 minutes). The dentifrice granules of this invention are free-flowing and can be readily dissolved in water such that they find use in various dentifrice applications including, but not limited to, anticavity mouthwash, antiseptic mouthwash, teeth whitening compositions, and the like. Given the uniformity of the instant granules, they can be packaged in a multi-dose container from which unit doses are withdrawn by a consumer or in single serving forms. In addition, by printing the granules in accordance with the method of this invention, fine particles or dust are reduced or eliminated during the preparation of the granules. Advantageously, the elimination of water provides a significant cost savings in terms of shipping and packaging.

[0057] In an aspect of the present invention, granules of are “free-flowing” in the sense that the surfaces of the dried granules are virtually free of oil or tacky material e.g., flavor, fragrance or active ingredient). In this respect, the dried granules do not agglomerate or clump. In certain aspects, the dried granules have less than 0.1%, 0.05%, 0.01%, 0.005%, 0.001% or 0.0005% free oil on the surface thereof.

[0058] In an aspect of the present invention, the granules are dry and have a water content of 15% or less, or more preferably 10% or less. In certain aspects, the dried granules have a water content of 4% to 10%, or more preferably 4% to 8%. In this respect, “dry,” “dried,” and “substantially dried” encompass those compositions with a water activity of 0.1 to 0.6, or more desirably 0.2 to 0.5, and most preferably from 0.2 to 0.4 wherein said levels of dryness can be achieved with or without secondary drying. [0059] In an aspect of the present invention, dried dentifrice granules are water-soluble and therefore easily dissolved in or miscible with water. In other words, the dentifrice granules are capable of forming a homogeneous solution with water at ambient conditions. As used herein, “ambient conditions” means 23°C ± 1.0°C and a relative humidity of, e.g., 50% ± 2%. In an aspect of the present invention, the granules have, based on morphology, a porous structure to facilitate dissolution in water. The porous structure can be reflected in percent porosity. In some aspects, water-solubility is with reference to the granule itself and not necessarily each component thereof. For example, the granule may include one or more water-insoluble components that may be suspended in water upon dissolution of the granule.

[0060] In certain aspects of the present invention, the granule has a dissolution time in water of less than 10 minutes. Preferably, the granule has a dissolution time in water of less than 9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes, 2 minutes, 1 minute, or 30 seconds. The dissolution time of granules is measured via a dissolution rate test, which is used to measure the dissolving speed of the granules. This dissolution rate test is conducted by adding 198.0 g of de-ionized water into a 400 mL transparent beaker at room temperature (25 °C). The beaker is placed on a a stir plate. A conductivity probe (Fisher Conductivity Meter) is placed into the beaker with a clamp. The conductivity meter is turned on and the stirring speed is set to 500 RPM. 2.0 g of granules are added to the mixing water, and the starting time recorded. When the conductivity meter reading reaches its plateau, the meter will flash “READY” status, and the total time for the granules to be fully dissolved is recorded. This total time is the dissolution time.

[0061] In an aspect of the present invention, granules are solid particles, pastilles or pellets. The granules may be of any desired shape and size, and may be spherical, rod-like, plate-like, tubular, square, rectangular, disk-like or regularly shaped flakes. However, the granules disclosed herein are generally non-fibrous. In particular, the granules have a substantially homogeneous or uniform size distribution, i.e., the size of the granules vary by less than ±20%, ±18%, ±16%, ±14%, ±12%, ±10%, ±9%, ±8%, ±7%, ±6%, ±5%, ±4%, ±3%, ±2%, or ±1% from the mean diameter of the granules. In one aspect, the granules have an average size of less than 10 mm in diameter. In particular aspects, the granules have an average size ranging from 0.5 mm to 10 mm, preferably from 1 mm to 7 mm, or more preferably 1 mm to 5 mm in diameter. In some aspects, the granules have a size of less than 10 mm and a size distribution of less than 20%. In particular aspects, the granules have a size in the range of 1 mm to 5 mm in diameter and have a size distribution of less than ±10%.

[0062] In so far as the granules are prepared from a homogenous slurry or homogenous blend and printed in a uniform shape, both the weight and density of the granules are also uniform or homogenous. In this respect, the weight and density distribution of the granules vary by less than ±10%, ±9%, ±8%, ±7%, ±6%, ±5%, ±4%, ±3%, ±2%, or ±1% from the mean weight and density of the granules. In one aspect, the granules have a bulk density in the range of 0.05 g/ml to 2 g/ml, or more preferably in the range of 0.1 g/ml to 1.5 g/ml. In other aspects, a single granule has an average weight in the range of 0. 1 mg to 10 mg, or more preferably in the range of 1 mg to 6 mg. In other aspect, the granules have an apparent density in the range of 0.5 g/ml to 2 g/ml, or more preferably in the range of 0.8 g/ml to 1.8 g/ml.

[0063] In an aspect of the present invention, granules have dentifrice applications and include one or more dentifrice active ingredients. The active ingredients can be in liquid form or solid form. The active ingredients can be water-soluble or water-insoluble. For water-insoluble active ingredients in solid form, pre-treatment like grinding or sieving may be required to prevent nozzle clogging. Examples of dentifrice active ingredients include, but are not limited to, fluorides for anticavity; essential oils (such as menthol, eucalyptol, methyl salicylate, thymol), triclosan, stannous fluoride or cetylpyridinium chloride for antiseptic; a hydrogen peroxide source (such as carbamide peroxide, sodium percarbonate, calcium peroxide, peroxydone, perbenzoic acid) or enzymatic agent for teeth whitening; chlorhexidine or essential oils for a therapeutic mouth rinse; strontium chloride or potassium nitrate for hypersensitivity control; or vitamins for a nutraceutical. In some aspects, the amount of the dentifrice active is from 0.1% to 90% (e.g., 0.2% to 70%, 0.3% to 50%, 0.4% to 20%, 0.5% to 10%, 1% to 5%, 1% to 10%, 40% and 70%, and 50% to 90%) by weight of the dry granules. By way of illustration, the amount of fluoride in anticavity mouthwash granules is in the range of 1% to 5%; the amount of cetylpyridinium chloride in antiseptic mouthwash granules is in the range of 1% to 5%; and the amount of H2O2 source in teeth whitening mouthwash granules is in the range of 50% to 90%. [0064] In accordance with an aspect of the instant invention, the rate of granule dissolution in a solvent can be controlled through porosity. Moreover, dissolution of the granule of the invention can be also controlled by granule size, granule morphology, including dissolution agents, or a combination thereof. Furthermore, the rate of dissolution of a granule in solvent, e.g. water, may be modulated by further including at least one dissolution aid. Dissolution aids of this invention facilitate dissolution in water by swelling, gas release, enzymatic activity, or increasing the porous structure of the granule after drying. In particular, dissolution aids can include, but are not limited to, disintegrants, sugar-based excipients, or effervescent agents/effervescent activators. In dentifrices where low turbidity is preferred, such as mouthwash solutions, it is preferable to include at least one water dissolution aid, in particular a polyol such as mannitol or sorbitol, so that the granule is fully dissolving in water. In dentifrices where turbidity is of no concern, water dissolution aids such are disintegrants or super disintegrants may be used.

[0065] A “disintegrant” refers to a substance that promotes disintegration of the solid granules in water to help achieve a sufficient dissolution rate. A “superdisintegrant” refers to a disintegrant that is effective in inducing the disintegration of solid granules at a lower concentration than conventional disintegrants. Examples of disintegrants include, but are not limited to, amylase, protease, cellulase, invertase, starch and derivatives thereof, cellulose and derivatives thereof, microcrystalline cellulose, hydrophilic colloidal substance such as alginate, alginic acid NF, or combinations thereof. Examples of superdisintegrants include cross-linked polymers such as cross-linked celluloses such as croscarmellose (cross-linked carboxymethyl cellulose), crospovidone (cross-linked polyvinyl pyrrolidone), cross-linked starches such as sodium starch glycolate and soy polysaccharides. Calcium silicate is an example of a non-polymeric super disintegrant. Calcium silicate is a relatively inert mineral characterized by high water absorption.

[0066] “Sugar-based excipients” are excipients or inactive substances composed of sugars that are highly water soluble, non-toxic, and often non-hygroscopic. Examples of sugar-based excipients of use as dissolution aids include, but are not limited to, sorbitol, mannitol, dextrose, xylitol, fructose, maltose, isomaltose, maltitol, lactitol, starch hydrolysate, polydextrose, or combinations thereof.

[0067] The term “effervescent agent” refers to a compound capable of generating bubbles in a liquid environment. In certain aspects, the presence of bubbles is caused by the formation of a gas, such as carbon dioxide. For example, when added to water, a salt such as bicarbonate causes a chemical reaction that releases carbon dioxide when properly activated, such as by dissolving and mixing with a suitable effervescent activator, e.g., an acid. In accordance with the present invention, the effervescence reaction extends beyond the time required to mix the granule in water thereby providing a sensation of freshness and facilitating removal of loose particles in the mouth.

[0068] In certain aspects, the effervescent agent of this invention is a bicarbonate salt or carbonate salt such as sodium carbonate, sodium bicarbonate, sodium percarbonate, potassium carbonate, potassium bicarbonate or a combination thereof. In certain aspects, the effervescent agent is sodium carbonate, sodium bicarbonate, sodium percarbonate, potassium carbonate, or potassium bicarbonate. In particular aspects, the granule is a teeth whitening granule including sodium percarbonate.

[0069] In other aspects, the granule further includes an effervescent activator. In certain aspects, the effervescent activator is an organic acid, inorganic acid, or a salt or partial salt of an organic acid or inorganic acid. In certain aspects, the effervescent activator is citric acid, ascorbic acid, malic acid, fumaric acid, tartaric acid, succinic acid, adipic acid, pyruvic acid, oxaloacetic acid, maleic acid, alpha-ketoglutaric acid, alginic acid, amino acids, aconitic acid, lactic acid, and acid salt such as, monosodium citrate or a combination thereof. In particular aspects, the effervescent activator is citric acid, malic acid, fumaric acid, tartaric acid, succinic acid, adipic acid, monosodium citrate, disodium citrate or combinations thereof.

[0070] In some aspects, the effervescent agent and effervescent activator are provided in separate granules. This is particularly advantageous when the granules are prepared in the presence of an aqueous solvent. Accordingly, one aspect of this invention provides for a dentifrice granule system composed of a first granule including an effervescent activator and a binder system; and a second granule including an effervescent agent and a binder system, wherein one or both of the first granule or second granule includes a dentifrice active. In accordance with this aspect, the binder system of the first granule and the second granule can be the same or different. Likewise, when the first and second granule both include a dentifrice, the dentifrice of the first granule can be the same or different than the dentifrice of the second granule. [0071] In accordance with another aspect, the effervescent agent and effervescent activator are provided in a single granule. Such granules are preferably prepared in the absence or substantial absence of an aqueous solvent. In accordance with this aspect, the slurry used to prepare the granules includes a nonaqueous solvent so that the effervescent agent and effervescent activator do not react and release gas during the preparation of granules. In some aspects, the slurry is prepared in the form of a paste.

[0072] To modulate one or more physical, mechanical, and/or thermal properties of the granules of this invention, the granules also include one or more fillers or a binder system. A “filler” refers to a substance that is added to provide sufficient mass and/or volume. In some aspects, the filler is a multifunctional filler that fulfills more than one function. For example, the filler may be used to adjust the physical properties of the print slurry to provide a uniform and easy to print composition; increase cohesion of the granule components; decrease friability of the granules; and/or increase the shelf-life of the granules. The filler may be aqueous soluble or aqueous insoluble. Examples of fillers of used in accordance with the instant invention include, but are not limited to, starch, maltodextrin, mannitol (e.g., [3-D-mannitol), sorbitol, xylitol, or any combination thereof.

[0073] A binder system for the purposes of this invention is composed of a solvent and a binder polymer. In certain aspects, the binder system is a multifunctional binder system that provides cohesion of the granule components; acts as a primary coating for unencapsulated material or as a secondary coating for encapsulated material thereby decreasing the frangibility of the encapsulated material; provides a UV, moisture, oxidization, or microbial barrier; and/or provides an intermedia for coloring or other decorative purpose.

[0074] The solvent of the binder system may be an aqueous solvent (e.g., water) or a nonaqueous solvent. Examples of nonaqueous solvents include, but not limited to, e.g., acetone, ethanol, ethyl acetate, ethyl lactate, glycerin, monoglycerides and diglycerides, monoglyceride citrate, hexanes, limonene, methanol, methyl ethyl ketone, methylene chloride, isopropanol, propylene glycol, triacetin, triethyl citrate, or any combination thereof. In certain aspects, the solvent of the binder system is non-toxic and suitable for use in a dentifrice application. In certain aspects, the binder solvent is water. In other aspect, the binding solvent is a nonaqueous or anhydrous solvent. [0075] The binder polymer may be a hydrophilic or amphiphilic polymer or a combination thereof. Examples of hydrophilic polymers of use in the binder system include, but not limited to, e.g., polyvinyl alcohol, polyvinylpyrrolidone (PVP), povidone, methylcellulose, ethylcellulose, sodium carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), polyethylene glycol (PEG), and polyacrylic acid. Amphiphilic polymers include, but not limited to, e.g., poly(l-vinylpyrrolidone-co-vinyl acetate), hydroxylpropyl cellulose (HPC); hydroxy propyl methyl cellulose (HPMC); PEG copolymers (polyethylene glycol-block-polycaprolactone (PEG-PCL); polyethylene glycol-block- polylactic acid (PEG-PLA), PEG-PEI copolymer, PEG-PGLA copolymer). In some aspects, the binder polymer is suitable for human consumption. In some aspects, the polymer used in binder is generally recognized as safe (GRAS). In particular aspects, the binder system is composed of ethyl lactate as solvent and a combination of a polyvinylpyrrolidone copolymer and polyethylene glycol as binder polymer.

[0076] In addition to the dentifrice active, dissolution aid, and filler or binder system, the granule of this invention may further include one or more solvents, colors, pigments, flavors, flavor modifiers (such as sweeteners), surfactants, emulsifiers, humectants, antimicrobial agents, lubricants, glidants, diluents, antioxidants, viscosity modifiers, chelating or sequestering agents, pH modifiers, adhesives, taste modulators and modifiers, or combinations thereof.

In an aspect of the present invention, granule include at least one emulsifier and/or surfactant. Surfactants are substances that adsorb at the interface between oil and water, thereby decreasing the surface tension. An emulsifier is a surfactant that stabilizes emulsions. Emulsifiers coat droplets within an emulsion and prevent them from coming together, or coalescing. The surfactant may be an anionic surfactant, nonionic surfactant, cationic surfactant, amphoteric surfactant, or a combination thereof. Example of surfactants include, e.g., sodium lauryl sulfate, polysorbates, poloxamers, sodium coconut monoglycerides sulfonate, glycerol fatty acid esters, propylene glycol fatty acid esters, polyethylene glycol (PEG), sorbitan fatty acid esters, taurine, sarcosine, or combinations thereof. In particular aspects, the surfactant is sodium lauryl sulfate, polysorbate 20, polysorbate 80, or poloxamer 407. Examples of emulsifiers for use in this invention include, but are not limited to, lecithin, monoglyceride, diglyceride, sodium stearoyl lactylate, celluloses, starches or modified starches, gums, sucrose esters and sucroglycerides, polyglycerol esters, polyglycerol polyricinoleate, sorbitan esters, pectin proteins (such as sodium caseinate) or combinations thereof.

[0077] In an aspect of the present invention, granules can further include one or more flavors. Examples of flavors that may be included in the dentifrice granules include, but are not limited to, menthol, thymol, eucalyptol, methyl salicylate, wintergreen oil, myrrh oil, fennel oil, tea tree oil, peppermint oil, lemon oil, spearmint flavor, mint flavor, vanilla extract, cinnamon, strawberry flavor, orange flavor, mango flavor, cherry flavor, bubblegum flavor, chocolate flavor, and the like, or combinations thereof. Certain flavor oils have low water solubility and require the use of ethanol and/or other solvents to facilitate the solubility in traditional mouthwash solutions. However, such low water solubility of flavor oils is generally not an issue in the granules of the present invention because the granule matrix can increase the water solubility of flavor oils.

[0078] Depending on presence and type of solvent included in the preparation of the present granule, certain ingredients may be encapsulated in a core-shell microcapsule. For example, in certain aspects, flavor oils are encapsulated. In other aspects, effervescent agents, effervescent activators, and hygroscopic materials such as citric acid may be encapsulated. The wall of such a core-shell microcapsule can be composed of one or more polymers. Suitable wall materials include starches based materials such as maltodextrins, cyclodextrins, CAPSUL® starches, HI-CAP® 100; celluloses such as cellulose acetate, methylcellulose, ethylcellulose, carboxymethyl cellulose (CMC), hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC); gums such as agar, gum acacia, locust gum, alginates, carrageenan, xanthan; proteins such as gelatin, caseinates, soy protein, pea protein, and whey protein; fatty acids such as phospholipids, sphingolipids, shea butter; waxes such as beeswax, lanolin, candelilla wax, carnauba wax, paraffin wax; natural and synthetic rubbers such as poly isoprenes; resins such as terpenes, melamine resin, Ureaformaldehyde resin, shellac, lacquer; other polymers and copolymers including water soluble polymers such as polyamide, cationic polyacrylamide, polyacrylic acid, poly(methacrylic acid), poly(N-vinylpyrrolidone), poly(vinylamine) hydrochloride, poly(2- vinylpyridine), poly(styrenesulfonic acid); hydroxy functional polymers such as polyvinyl alcohol, poly(2-hydroxyethyl methacrylate); biodegradable polymers such as polyethylene glycol, polycaprolactone, polycaprolactam, polyglycolide, polylactide, polyhydroxybutyrate, chitosan, hyaluronic acid; polyacrylates such as polymethacrylate, polymethyl methacrylate, polyvinyl acetate, polybutyl acrylate; polystyrenes; polyurethanes; silicas such as SBA-15, MCM 41; and derivatives and mixtures thereof. [0079] In accordance with an aspect of the present invention, granules are produced by preparing a homogenous slurry; printing discrete droplets of the slurry onto a non-stick surface, said droplets having a uniform size, weight and density; and drying the printed droplets of slurry to produce free-flowing, water-soluble granules. A surface is considered “non-stick” when an adherent material can be easily removed without significant force or is completely prevented from adhering altogether.

[0080] In an aspect of the present invention, a method for producing granules includes the steps of (a) printing discrete droplets of a first slurry including an effervescent activator and a binder system onto a non-stick surface, said droplets having a uniform size, weight and density; (b) printing discrete droplets of a second slurry including an effervescent agent and a binder system onto the non-stick surface, said droplets having a uniform size, weight and density; (c) drying the printed droplets of (a) and (b) to produce the free-flowing, water-soluble dentifrice granule system, wherein one or both of the first slurry or second slurry includes a dentifrice active.

[0081] In another aspect of the present invention, dentifrice granules are produced by (a) preparing a homogenous slurry including (i) a dentifrice active, (ii) a dissolution aid, and (iii) a filler or binder system; (b) printing discrete droplets of the slurry onto a non-stick surface, said droplets having a uniform size, weight and density; and (c) drying the printed droplets of slurry to produce free-flowing, water-soluble granules.

[0082] In a further aspect of the present invention, the method includes the step of emulsifying in an aqueous phase a dentifrice active ingredient, one or more fillers, and optionally one or more flavor or essential oils, emulsifiers, polymers, surfactants, emulsion stabilizers, flavor modifiers, colors and/or viscosity modifiers to prepare a homogenous printing slurry. The homogenous printing slurry is then printed/dispensed/deposited on a non-sticky substrate in discrete droplets. As used herein, the term “discrete” refers to droplets, which under the naked eye, are separate from one another, i.e., there is empty space between droplets. Once printed, the droplets are then dried, and optionally harvested and packaged either in bulk or individual dosage forms or servings.

[0083] In accordance with an aspect of the present invention, the method includes the steps of blending at least one dentifrice active ingredient with a dissolution aid and optionally one or more flavor or essential oils, emulsifiers, polymers, surfactants, emulsion stabilizers, flavor modifiers, colors and/or viscosity modifiers to prepare a dentifrice active dry blend; blending the dentifrice active dry blend with a binder system to prepare a homogenous printing slurry; printing/dispensing/depositing the slurry on a non-sticky substrate in discrete droplets; drying the droplets; and optionally harvesting and packaging the droplets either in bulk or individual dosage forms or servings.

[0084] In accordance with an aspect of the present invention, the morphology of granules can be controlled by adjust processing parameters, such as sonication power or high shear mixing power when preparing the slurry thereby generating coarse or fine bubbles in feed slurry.

[0085] Depending on the homogenous slurry to be printed and dried, the feed can have a viscosity in the range of 100 cP (centipoise) or mPa-s (millipascal-second) to 20,000 cP or mPa-s. In some embodiments, the feed has a viscosity of more than 100 cP, more than 200 cP, more than 300 cP, more than 400 cP, more than 500 cP, more than 600 cP, more than 700 cP, more than 800 cP, more than 900 cP or more than 1000 cP. In other embodiments, the feed has a viscosity of less than 20, 000 cP, 15, 000 cP, 10,000 cP, 9000 cP, less than 8000 cP, less than 7000 cP, less than 6000 cP, or less than 5000 cP. The viscosity of the dispensing slurry was measured with AMETEK Brookfield DV3T Rheometer with spindle RV-06 at speed of 50-200 rpm at room temperature.

[0086] Preferably, the homogenous slurry is printed, dispensed or deposited directly on a substrate in discrete, predefined shapes. Preferably, the substrate is non-stick surface (e.g., a movable conveyer belt). In addition, the homogenous slurry can be printed on a non-stick surface in a predefined pattern, in particular a dot pattern. Preferably, the pattern is selected to facilitate drying, post-processing, and product quality. In some aspects, the printed shape is a three-dimensional dot, such as a mini -pastille or mini-troche, e.g., a 0.04 mm³ to 10 mm³. In another embodiment, a plurality of dots is printed in a pattern or array such that the dots are evenly distributed and spaced for optimal drying, post-processing, and product quality, e.g., center point-to-center point spacing of 1 to 10 mm between dots. Alternatively, the spacing of the dots can be a factor of their diameter, e.g., a center-to- center spacing of “ID” means the edges of the dots are just touching other, whereas “2D” means that center-to-center spacing of the dots is two times the diameter. [0087] Preferably, the print assembly is adapted to print a homogenous slurry having a viscosity in the range of 100 cP to 20,000 cP. More preferably, in the range of 1,000 cP to 10,000 cP. In some aspects, the print assembly is adapted to print a homogenous slurry having a viscosity at least 200 cP, 300 cP, 400 cP, 500 cP, 600 cP, 700 cP, 800 cP, 900 cP, 1000 cP, 2000 cP, 3000 cP, 4000 cP, 5000 cP, 6000 cP, 7000 cP, 8000 cP, 9000 cP, or 10000 cP.

[0088] The homogenous slurry can be printed by valve jetting, auger dispensing, extrusion, cylinder deposition method, or any other printing methods that lend themselves to this application. In particular aspects, the homogenous slurry is printed using a noncontact print assembly, e.g., an inkjet-type print head or array of nozzles that drop or deposit the material on a surface; or a contact print assembly, e.g., flat bed screen, rotary screen, reverse gravure or flexography print assembly. In particular embodiments, the print assembly is a non-contact print assembly. Suitable printing assemblies for use in this invention are disclosed in US 2022/0071862 Al, incorporated herein by reference in its entirety.

[0089] Granule size can be controlled by varying nozzle size of the printing assembly. Generally speaking, the smaller the granule size, the quicker the dissolution rate. For example, whereas an auger dispensing device with a 0.7 mm nozzle plate can produce granules in the size range of 0.7 mm to 2 mm, an auger dispensing device with a 1.1 mm nozzle can produce granules in the size range of 1.1 mm to 3.5 mm. In some aspects, the fragrance or flavor is provided at a droplet diameter of between 100 microns and 10 mm, or more preferably between 425 microns and 1 mm. As is conventional in the art, a droplet smaller than 425 microns (z.e., a particle passing through a 40-mesh sieve) is considered dust. While particle size in the feed slurry affects nozzle size selection, viscosity of feed slurry can affect the pressure required to generate granules. The smaller droplets can be obtained with a smaller nozzle diameter and higher pressures, whereas a larger nozzle diameter and lower pressures are used to obtain larger droplet sizes.

[0090] For convenience, the source of homogenous slurry, is often maintained at nearambient temperatures; however, this is not a limitation of the disclosed system or method. Generally, the temperature of the source of homogenous slurry can range from 0°C to 80°C or even higher. Temperatures of less than 0°C may also be utilized, especially when there are stability concerns about the feed. Likewise, the rest of the system, in particular the print assembly and optional pump, can be used at any suitable temperature that does not alter the homogenous slurry. In certain embodiments, the system is at or about room temperature (e.g., 20°C to 25°C). However, when the viscosity of a homogenous slurry is high, the homogenous slurry can optionally be heated to, e.g., 32°C to 80°C without altering the homogenous slurry.

[0091] The printed droplets can be dried by a variety of suitable methods including the use of convectional heat, infrared drying, vacuum drying, pressure drying, or freeze drying. In some aspects, the droplets are dried using infrared. In some aspects, the homogenous slurry feed is printed on the movable product conveyor passing through or adjacent to a drying component to facilitate drying of the granules. In this respect, the air of the drying component is in fluid contact with the homogenous slurry feed printed on the movable product conveyor. Drying air circulates through the drying component, streaming over and around the printed feed to evaporate moisture. In some aspects, the flow of the drying air is essentially parallel to the movable product conveyor. In other aspects, the flow of the drying air is in a straight or rotary downward direction toward the movable product conveyor. In certain aspects, the flow of the drying air is in the same direction as the product flow. In other aspects, the flow of the drying air is in the opposite direction as the product flow.

[0092] The air supplied to the drying component may be air from the surrounding environment, a gas other than air, or a combination thereof. Inert gases, for example nitrogen gas and carbonate gas, can be used. For readily oxidizable substances, inert gases may be preferred.

[0093] The temperature of the air supplied to the drying component is ideally in the range of 30°C to 160°C, preferably 30°C to 1 KFC, more preferably 40°C to 100°C, and most preferably 40°C to 90°C. In certain aspects, the temperature of the air is less than 100°C. When the air is above ambient room temperature, the drying system can further include an air heater to heat the air. The air heater may be configured to operate using either electrical power or gas. Accordingly, in some embodiments, the system can further include a gas radiant heater or electric heater. The term “gas radiant heater” means devices which produce substantially radiant heat by combusting gas. The term “electric radiant heater” means devices which produce substantially radiant heat by drawing electrical current. Various forms of such heaters are known in the art. [0094] The relative humidity (RH) of the air supplied to the drying component may be 35% RH or less, preferably 15% RH or less, more preferably 7% RH or less, and most preferably 1% RH or less. When the air RH is above ambient levels, the system can further include air dehumidifier configured to supply desiccated air to the drying component. Accordingly, the system can have both a dehumidifying and drying function. A drying component capable of blowing a high volume of desiccated air with a dew point of less than 5 °C is preferable. For a drying component with no dehumidifying function, the drying component can be modified to include a dry dehumidifier, e.g.. a honeycombtype rotary dehumidifier (e.g., Nichias Corporation or Sweden PROFLUTE Corporation). [0095] To facilitate drying of the printed droplets, the system can be modified to include a supplemental energy source. Ideally, the supplemental energy source provides dry radiant heat, i.e., heat energy which is transmitted from one body to another by the process generally known as radiation, as differentiated from the transmission of heat from one body to another by the processes generally known as conduction and convection. [0096] Dry radiant heat sources are known in the art and can attain high temperatures and can produce large quantities of radiant heat energy. Such heaters can attain temperatures of at least 100°C and can attain temperatures significantly greater than 100°C. The high temperatures attainable by these heaters can be beneficial in producing large amounts of heat energy. In addition, the temperature of the heater, and thus the amount of radiant heat energy produced, can be relatively quickly changed and can be easily regulated by proportional modulation thereof. Also, such heaters generally tend to be relatively light in weight compared to other heat sources and are generally resistant to shock and vibration.

[0097] Examples of suitable dry radiant heat sources include, but are not limited to, infrared and other light devices, electric radiant heaters, and radiant gas heaters. Since electric radiant heaters such as quartz heaters and ceramic heaters draw electrical power for operation, such heaters can be operated either from a portable generator, or from a permanent electrical power grid. Similarly, radiant gas heaters can be operated either from a portable gas supply, such as a liquified natural gas tank, or from a gas distribution system such as an underground pipeline system. Furthermore, heaters such as those discussed above are generally known to provide long, reliable operating life and can be serviced easily. Additional sources of energy include, but are not limited to, microwaves or radio frequency waves.

[0098] The supplement energy source can be configured to direct radiant heat toward the lower side of the movable product conveyor, i.e., the side opposite that which the feed is printed. However, in an alternative embodiment of the present invention, a supplemental energy source directs radiant heat toward the side of the movable product conveyor which the feed is printed. In yet another alternative embodiment, reflectors or the like can be employed to direct radiant heat from the supplement energy source toward the printed feed. Movable product conveyors adapted to include one or more supplemental energy sources are known in the art and described, e.g., in US 6,539,645, US 7,441,344, US 8,984,763, US 9,068,777, US 9,243,843, US 9,073,711 and US 9,550,629.

[0099] To allow for transfer of energy from the supplement energy source, the movable product conveyor can be fabricated from a material which is substantially transparent to radiant heat and is also able to withstand temperatures of up to 150°C. In some embodiments, the movable product conveyor is fabricated from a material comprising plastic. The term “plastic” means any of various nonmetallic compounds synthetically produced, usually from organic compounds by polymerization, which can be molded into various forms and hardened, or formed into pliable sheets or films. In certain aspects, the movable product conveyor is fabricated from an acrylic and polyester. Such materials, when used in the fabrication of a movable product conveyor, are known to have the desired thermal radiation transmission properties for use in the present invention. Further, plastic resins can be formed into a uniform, flexible sheet, or into a seamless, endless belt, which can provide additional benefits. In other aspects, the movable product conveyor is fabricated from stainless steel or other suitable material coated with a nonstick coating such as TEFLON (a polytetrafluoroethylene coating).

[00100] The speed, or rate of movement, of the movable product conveyor as well as temperature and rate of air flow can affect the process of drying the printed feed. For example, a relatively slow speed of the movable product conveyor (e.g., -0.05 m/sec) can increase the amount of heat which is absorbed by the printed feed because the slower speed will cause the printed feed to be exposed to the heat for a longer period of time.

Conversely, a relatively fast speed of the movable product conveyor (e.g., -0.9 m/sec) can decrease the amount of heat which is absorbed by the movable product conveyor because the faster speed will result in less exposure time during which the movable product conveyor is exposed to the heat. Accordingly, the printing system used in accordance with the method of this invention can include one or more sensors and controllers for regulating the temperature of the heat sources 80, 100; regulating the speed of the movable product conveyor 50; and/or regulating the rate of drying air flowing over printed feed. In some embodiments, the movable product conveyor speed is in the range of 0.05 m/sec and 1.0 m/sec. In some aspects, the feed is dried quickly to provide a more shelled or porous granule. In particular, the droplets have a drying time of less than 10 minutes, preferably less than 5 minutes, more preferably about 2 minutes. By way of illustration, a drying process can include drying with an infrared lamp, optionally in combination with convection heating. Using such a system, the drying time may be in the range of 2-5 minutes or can be 10 or more minutes depending on the product. In addition, while some droplets can dry at very high temperature, for example 80°C, other droplets, e.g., antiseptic mouthwash granules with cetylpyridium chloride, are dried at a temperature lower than 70°C, preferably less than 65 °C, because the melting temperature of cetylpyridium chloride is 77°C.

[00101] Dried granules exiting the drying component may passively fall off the movable product conveyor and be collected or harvested and optionally packaged as a bulk product in single dose or single serving forms and multi-dose forms, including for refill. The dried granules may be packaged in a sachet, bottle, dissolvable pouch, granular sealer, cup with sealable lid, stick pack, etc.

[00102] While an aspect of the present invention is directed to the preparation of dentifrice granules for use in preparing antiseptic mouthwashes, anticavity mouthwashes, teeth whitening compositions, or therapeutic or nutraceutical mouth rinses, the principles described herein may also be used it the preparation of cleaning agent granules, disinfectant granules, biologies granules, toiletry granules, hair product granules (e.g., shampoo, conditioner or hair rinse), or scent granules.

[00103] In accordance with an aspect of the present invention, the dentifrice granules of the present invention can be anticavity, antiseptic, anti-plague, anti-gingivitis, and/or teeth- whitening. [00104] In an aspect of the present invention, a free-flowing, water-soluble dentifrice granule is presented having a flavor agent, a dentifrice active and an emulsifier, wherein said granule has a porosity of from about 10% to about 70%.

[00105] Preferably, the flavor agent is menthol, thymol, eucalyptol, methyl salicylate, wintergreen oil, myrrh oil, fennel oil, tea tree oil, peppermint oil, lemon oil, spearmint oil, mint flavor, vanilla flavor, cinnamon flavor, berry flavor (preferably strawberry, raspberry or blueberry), orange flavor, mango flavor, cherry flavor, bubblegum flavor, chocolate flavor or a combination thereof.

[00106] More preferably, the flavor agent is peppermint oil. Preferably, the dentifrice granule has flavor retention of more than 75%.

[00107] Preferably, the dentifrice active is a fluoride, an essential oil, triclosan, cetylpyridinium chloride, a hydrogen peroxide source, an enzyme, chlorhexidine, strontium chloride, potassium nitrate or a vitamin. More preferably, the dentifrice active is an essential oil. Preferably, the essential oil is menthol, eucalyptol, methyl salicylate, myrrh oil, fennel oil, tea tree oil or thymol.

[00108] In other preferred embodiments, the dentifrice active is a fluoride. Preferably, the fluoride is amine fluoride, silver diamine fluoride, sodium monofluorophosphate, stannous fluoride or sodium monofluorophosphate.

[00109] In still other preferred embodiments, the dentifrice active is a hydrogen peroxide source. Preferably, hydrogen peroxide source is carbamide peroxide, sodium percarbonate, calcium peroxide, peroxydone or perbenzoic acid.

[00110] Preferably, the emulsifier is lecithin, monoglyceride, diglyceride, sodium stearoyl lactylate, celluloses, starches or modified starches, gums, sucrose esters, sucroglycerides, polyglycerol esters, polyglycerol polyricinoleate, sorbitan esters, pectin, proteins or combinations thereof.

[00111] Preferably, the porosity is about 10% to about 70%. More preferably, the porosity is about 30% to about 60%.

[00112] In some preferred embodiments, the granule also has a disintegrant. Preferably, the disintegrant is an enzyme (such as amylase, protease, cellulase, or invertase), starch and/or starch derivatives (such as sodium starch glycolate), cellulose and/or cellulose derivatives (such as croscarmellose sodium, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and microcrystalline cellulose), a hydrophilic colloidal substance (such as alginate, alginic acid NF), natural gums (such as guar gum, xantham gum, locust bean gum), crosslinked polyvinylpyrrolidone, soy polysaccharides or combinations thereof.

[00113] In other preferred embodiments, the granule also has a surfactant. Preferably, the surfactant is sodium lauryl sulfate, polysorbate, poloxamers, sodium coconut monoglycerides sulfonate, glycerol fatty acid ester, propylene glycol fatty acid ester, polyethylene glycol (PEG), sorbitan fatty acid ester, sucrose ester, taurine, sarcosine, or combinations thereof.

[00114] In still other preferred embodiments, the granule also has an effervescent agent. Preferably, the effervescent agent is a bicarbonate salt or carbonate salt such as sodium carbonate, sodium bicarbonate, sodium percarbonate, potassium carbonate, potassium bicarbonate or a combination thereof.

[00115] Preferably, the granule also has an effervescent activator. Preferably, the effervescent activator is citric acid, ascorbic acid, malic acid, fumaric acid, tartaric acid, succinic acid, adipic acid, pyruvic acid, oxaloacetic acid, maleic acid, alpha-ketoglutaric acid, alginic acid, amino acids, aconitic acid, lactic acid, and acid salt such as monosodium citrate, disodium citrate, or a combination thereof.

[00116] Preferably, the granule dissolves in water at 23 °C ± 1.0°C in less than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 minute.

[00117] In another aspect of the present invention, a method is presented for producing a free-flowing, water-soluble dentifrice granule having a porosity of from about 10% to about 70%, the method having the steps of:

[00118] (a) dispensing discrete droplets of a slurry having a flavor agent, a dentifrice active and an emulsifier onto a non-stick surface;

[00119] (b) drying the dispensed droplets of (a) to produce the free- flowing, water- soluble dentifrice granule having the porosity of from about 10% to about 70%.

[00120] Preferably, the flavor agent is menthol, thymol, eucalyptol, methyl salicylate, wintergreen oil, myrrh oil, fennel oil, tea tree oil, peppermint oil, lemon oil, spearmint oil, mint flavor, vanilla flavor, cinnamon flavor, berry flavor (preferably strawberry, raspberry or blueberry), orange flavor, mango flavor, cherry flavor, bubblegum flavor, chocolate flavor or a combination thereof. Preferably, the dentifrice granule has flavor retention of more than 75%. [00121] Preferably, the dentifrice active is a fluoride, an essential oil, triclosan, cetylpyridinium chloride, a hydrogen peroxide source, an enzyme, chlorhexidine, strontium chloride, potassium nitrate or a vitamin. More preferably, the dentifrice active is an essential oil. Preferably, the essential oil is menthol, eucalyptol, methyl salicylate, myrrh oil, fennel oil, tea tree oil or thymol.

[00122] In other preferred embodiments, the dentifrice active is a fluoride. Preferably, the fluoride is amine fluoride, silver diamine fluoride, sodium monofluorophosphate, stannous fluoride or sodium monofluorophosphate.

[00123] In still other preferred embodiments, the dentifrice active is a hydrogen peroxide source. Preferably, hydrogen peroxide source is carbamide peroxide, sodium percarbonate, calcium peroxide, peroxydone or perbenzoic acid.

[00124] Preferably, the emulsifier is lecithin, monoglyceride, diglyceride, sodium stearoyl lactylate, celluloses, starches or modified starches, gums, sucrose esters, sucroglycerides, polyglycerol esters, polyglycerol polyricinoleate, sorbitan esters, pectin, proteins or combinations thereof.

[00125] Preferably, the porosity is about 10% to about 70%. More preferably, the porosity is about 30% to about 60%.

[00126] In some preferred embodiments, the granule also has a disintegrant. Preferably, the disintegrant is an enzyme (such as amylase, protease, cellulase, or invertase), starch and/or starch derivatives (such as sodium starch glycolate), cellulose and/or cellulose derivatives (such as croscarmellose sodium, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and microcrystalline cellulose), a hydrophilic colloidal substance (such as alginate, alginic acid NF), natural gums (such as guar gum, xantham gum, locust bean gum), crosslinked polyvinylpyrrolidone, soy polysaccharides or combinations thereof.

[00127] In other preferred embodiments, the granule also has a surfactant. Preferably, the surfactant is sodium lauryl sulfate, polysorbate, poloxamers, sodium coconut monoglycerides sulfonate, glycerol fatty acid ester, propylene glycol fatty acid ester, polyethylene glycol (PEG), sorbitan fatty acid ester, sucrose ester, taurine, sarcosine, or combinations thereof.

[00128] In still other preferred embodiments, the granule also has an effervescent agent. Preferably, the effervescent agent is a bicarbonate salt or carbonate salt such as sodium carbonate, sodium bicarbonate, sodium percarbonate, potassium carbonate, potassium bicarbonate or a combination thereof.

[00129] Preferably, the granule also has an effervescent activator. Preferably, the effervescent activator is citric acid, ascorbic acid, malic acid, fumaric acid, tartaric acid, succinic acid, adipic acid, pyruvic acid, oxaloacetic acid, maleic acid, alpha-ketoglutaric acid, alginic acid, amino acids, aconitic acid, lactic acid, and acid salt such as monosodium citrate, disodium citrate, or a combination thereof.

[00130] Preferably, the granule dissolves in water at 23 °C ± 1.0°C in less than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 minute.

[00131] Preferably, in a granule presented in accordance with the instant invention, the dentifrice active is one or more of an anticavity agent, an antimicrobial, an antiseptic agent, a tooth whitening agent, a tooth desensitizing agent, a disclosing agent, dental preventative or aesthetic enhancers.

[00132] More preferably, the dentifrice active is an anticavity agent. Preferably, the anticavity agent is a fluoride, a xylitol or a remineralizer. More preferably, the anticavity agent is a remineralizer. Preferably, the remineralizer is hydroxyapatite, silver nanoparticles, calcium phosphate, casein phosphopeptide-amorphous calcium phosphate, calcium glycerophosphate, or other dentifrice designed to rehabilitate dentin or enamel. [00133] In other preferred embodiments, the dentifrice active is an antimicrobial agent. Preferably, the antimicrobial agent is triclosan, an essential oil, cetylpyridinium chloride, chlorhexidine, chlorine dioxide, or aloe vera.

[00134] In still other preferred embodiments, the dentifrice active is one or more enzymes. Preferably, the one or more enzymes are papain, bromelain, tannase, or glucose oxidase.

[00135] In still other preferred embodiments, the dentifrice active is a tooth desensitizing agent. Preferably, the tooth desensitizing agent is potassium nitrate, strontium chloride, strontium acetate, baking soda, fluorides, bonding resins, oxalate, arginine, casein phosphopeptide-amorphous calcium phosphate, calcium phosphate, calcium carbonate, gluma, or vitamins.

[00136] In still other preferred embodiments, the dentifrice active is a dental preventative. Preferably, the dental preventative is an anti-gingivitis, anti-plaque, antifungal agents. [00137] Preferably, in a method presented in accordance with the instant invention, the dentifrice active is one or more of an anticavity agent, an antimicrobial, an antiseptic agent, a tooth whitening agent, a tooth desensitizing agent, a disclosing agent, dental preventative or aesthetic enhancers.

[00138] More preferably, the dentifrice active is an anticavity agent. Preferably, the anticavity agent is a fluoride, a xylitol or a remineralizer. More preferably, the anticavity agent is a remineralizer. Preferably, the remineralizer is hydroxyapatite, silver nanoparticles, calcium phosphate, casein phosphopeptide-amorphous calcium phosphate, calcium glycerophosphate, or other dentifrice designed to rehabilitate dentin or enamel. [00139] In other preferred embodiments, the dentifrice active is an antimicrobial agent. Preferably, the antimicrobial agent is triclosan, an essential oil, cetylpyridinium chloride, chlorhexidine, chlorine dioxide, or aloe vera.

[00140] In still other preferred embodiments, the dentifrice active is one or more enzymes. Preferably, the one or more enzymes are papain, bromelain, tannase, or glucose oxidase.

[00141] In still other preferred embodiments, the dentifrice active is a tooth desensitizing agent. Preferably, the tooth desensitizing agent is potassium nitrate, strontium chloride, strontium acetate, baking soda, fluorides, bonding resins, oxalate, arginine, casein phosphopeptide-amorphous calcium phosphate, calcium phosphate, calcium carbonate, gluma, or vitamins.

[00142] In still other preferred embodiments, the dentifrice active is a dental preventative. Preferably, the dental preventative is an anti-gingivitis, anti-plaque, antifungal agents.

[00143] Preferably, in a granule presented in accordance with the present invention, porosity is controlled by formulation parameters and processing conditions.

[00144] Preferably, in a granule presented in accordance with the present invention, wherein the porosity in the range of about 30% to about 60%, the granule exhibits an improved dissolution rate and favorable friability characteristics.

[00145] The invention is described in greater detail by the below non-limiting examples. Without further elaboration, it is believed that one skilled in the art can, based on the description herein, utilize the present invention to its fullest extent. All publications cited herein are incorporated by reference in their entirety. EXAMPLES

[00146] A free flowing and dust-free dentifrice granule system with a dentifrice active, were made to have uniform size, weight, and density. The granule system possesses a porous structure with porosity in the range of 10-70%. In accordance with the instant invention, it was discovered that high porosity expedites the rapid dissolution of granules, offering advantages over effervescent compounds or disintegrants within the granule system.

[00147] For water soluble granules, the factors that affect their dissolution rate include, but are not limited to, 1) granule strength caused by binding agents, 2) solubility of ingredients in the granules, 3) temperature of water, 4) surface area of the granules, and 5) the amount of agitation that occurs when granules and water are mixed. For granules, containing certain ingredients, made by certain binding agents, dissolving in water under certain conditions (temperature, and agitation), the dissolution rate of the granules, as discovered in accordance with the present invention, is dramatically impacted by the surface area of granules. In this regard, it was discovered in accordance with the instant invention that a given quantity of granules dissolve faster when a greater surface area is exposed to solvent. In one aspect of the present invention, surface area can be increased by increasing the porosity of granules. Porosity, also called “void fraction”, is a fraction of the void volume over the total volume. In accordance with the present invention, granule porosity was found not only to affect dissolution but also friability of granules. Therefore, in accordance with the instant invention, the specific porosity of granules can be designed for specific application.

[00148] Granule porosity can be affected by formulation and process. In formulation, the using of foaming agents introduces a uniform dispersion of a gaseous phase in a print slurry and also in the corresponding dried granules. Processes which impact porosity include both the printing process and the drying process. In the printing process, the print method may affect porosity. For example, in a thick stencil print, pressure is applied to a thick paste to achieve 3D structures, the resultant granules are compact with relatively low porosity. In the drying process at atmospheric pressure, the drying temperature can affect porosity. At high temperatures, the water in the wet slurry quickly gasifies, and evaporates rapidly, leading to the formation of large voids or high porosity in the dried structure. At low temperatures, the water in wet slurry slowly volatilizes, leading to the formation of tiny voids or low porosity in the dried structure. Therefore, by controlling drying temperatures, granule porosity can be manipulated to provide a desired void fraction. Example 1

[00149] Section 1 : fast dissolving porous granules

[00150] In this application of dentifrice granule system, its fast dissolution rate was achieved with a highly porous structure. The high porosity was achieved by manipulating both the formulation and process.

[00151] Anticavity mouthwash granules in this embodiment are just one example of the fast-dissolving dentifrice granule system. The porous anticavity mouthwash granules are fabricated with formulation containing foaming agents (Poloxamer 407 and SLS), using jet valve printing, with Infrared light drying.

[00152] The anticavity mouthwash granules were created using the formulation as detailed in the Table 1. The solid content of the print slurry for the granules produced with jet valving deposition method was 65%. The procedure for preparing the print slurry is detailed below:

[00153] To 350 g of distilled water was added OSA-modified starch and maltodextrin. The mixture was stirred with an overhead mixer (Lightnin GP2 mixer) at speed of 600-800 rpm for 20 minutes and flavor oil (such as peppermint oil) was slowly added while mixing. Once all the flavor oil was added, the mixture was allowed to stir at 600-800 rpm for an additional 5 minutes and then emulsified using an overhead high shear mixer (IKA T25 digital ultra-turrax dispenser) at 13,500 rpm for 3-5 minutes. The emulsion was placed back on overhead mixer. Surfactants (such as ethylene oxide and propylene oxide copolymer, Sodium lauryl sulfate), active, polyols, sweetener and color were subsequently added with stirring for another 20 minutes using overhead mixer (600-800 rpm). The viscosity of the resulting printing slurry was determined and found to be about 8,000- 15,000 cP at room temperature.

[00154] The jet valve printing parameters are listed in Table 2. The wet deposited dots on substrate were placed into an infrared light dryer, and the drying conditions are detailed in Table 3. The obtained granules were round dome shaped, with the bottom side flat on substrate. Visual inspection revealed that there were many open pores in each. Physical characterizations of obtained granules are summarized in Table 4. Table 1: formulation of dried anticavity mouthwash granules 22X.

Table 2: Jet valve print parameters.

Table 3: drying parameters.

Table 4: Physical characterization of anticavity mouthwash granules made by jet valve printing.

The uniform porous anticavity mouthwash granules manufactured by the jet valve printing and quick infrared light drying methods are in the size range of 2.5-3mm, with single granule weight in the range of 1-2 mg, are characterized with porosity of 55.5% with Mercury Intrusion Porosimeter (MIP) method, and can quickly dissolve in tap water (in the temperature range of 18-23 °C) in about 2min. These anticavity mouthwash granules can be used for multi-dose refill, dissolving 7.5 g of granules in 500 ml of water, or used for single serving, dissolving 0.3 g of granules in 20 ml of water. The flavor retention of peppermint oil in these anticavity mouthwash granules was characterized with GC-FID using a 25m 0.2mm 0.33pm Ultra-1 column. The flavor retention of freshly made granules was about 82.4%. The flavor retention of 2-month aged granules stored at ambient conditions was about 81.6%.

Example 2

[00155] Section 2: slow dissolving compact granules

[00156] To show porosity is a key factor affecting the dissolution time of granules, another batch of compact granules with same the formulation as detailed in Table 1 were manufactured by stencil print.

[00157] The solid content of the print paste for stencil print was 83%. The procedure for preparing the print paste was detailed below. Firstly, all the dry ingredients in Table 1 were mixed well (except flavor oil) in a tumbler mixer for about 1 hour. Secondly, flavor oil was mixed into the above mixture in a dough kneading machine (KitchenAid) at low speed for about 2 min. Thirdly, water was added to the mixture in the second step in the kneading machine, the mixture was allowed to knead for about 5min until a uniform paste was obtained at low speed. The print paste had minimum flowability.

[00158] A 0.016” thick stencil with hexagon pattern (hexagon side length was 3mm) was used for stencil printing. The print paste was stenciled on a non-stick substrate (PTFE coated fiberglass conveyor belt). [00159] To minimize porosity, the stencil printed granules were dried at room temperature. The obtained compact granules were in the shape of flat hexagon disks. Their physical characterizations are summarized in Table 5.

Table 5: Physical characterizations of anticavity mouthwash granules made by stencil printing.

[00160] As set forth in Table 5, the stencil printed flat hexagon disks are very compact, with a porosity of about 20.2%. These less porous granules took about 6 min to dissolve in tap water (in the temperature range of 18-23°C). Hence, lower granule porosity leads to a longer dissolution time and a slower dissolution rate.

Example 3

[00161] Section 3 : porosity affected by foaming agents

[00162] Examples 1 and 2 show that granule porosity is impacted by the employed printing methods. In this section, it is demonstrated that foaming agents may also affect granule porosity. Two sets of anticavity mouthwash granules, 22G and 22J, produced from slurries with the same solid content levels, but varying foaming agent types and usage levels in formulations detailed in Table 6, were printed using the same jet-valving printing method and subsequently dried using an identical drying process. The print slurry preparation method was the same as in Example 1. The jet-valve printing parameters are listed in Table 7. The drying method used was infrared light (one 550W bulb, output at 65°C) for 3min, then room temperature drying overnight.

[00163] The physical appearance of anticavity mouthwash granules, 22G and 22J, examined. Both 22G and 22J granules are fusiform shape. Table 8 below summarizes pertinent physical characterizations of the two sets of granules. [00164] The resulting granules exhibited disparate porosity levels (38% vs 23%), leading to variations in dissolution times (2 min vs 6 min). Thus, the use of foaming agents in granules can affect granule porosity and, thus, affect dissolution of granules.

Table 6: Emulsion formulations for anticavity mouthwash granules 22G and 22J.

Table 7: Jet valve print parameters.

Table 8: physical characterizations of anticavity mouthwash granules 22G and 22J.

Example 4

[00165] Section 4: porosity affected by drying methods.

[00166] Example 2 shows that printing methods affect porosity. Here it is shown that drying methods also affect granule porosity.

[00167] Anticavity mouthwash granules were produced by printing a slurry with the same formulation as presented in Table 1. The preparation of print slurry and the printing of granules followed the same protocol as set forth in Example 1. The printed granules were dried under different conditions: ambient drying overnight, heat drying at 50°C for 60 minutes or infrared (IR) drying at 80-95°C for 2min. The granules were examined with both the naked eye and a microscope. Examination with the naked eye revealed that there was one major pore in the center of air-dried granule. Microscopic evaluation confirmed the one major pore and revealed a few minor pores in the air-dried granule. Examination with the naked eye also revealed that there was one major pore in the center of heat-dried granule. Microscopic evaluation confirmed the one major pore and revealed more minor pores in the heat-dried granule. There were many major pores in IR-dried granules observed with both the naked eye and a microscope. Physical characterizations of the granules from the three different drying conditions are summarized in Table 9. From the results, it can be seen that increasing the severity of the drying conditions (temperatures) resulted in the formation of more porous structures in the granules which led to faster dissolution as shown in Table 9. Therefore, the dissolution of time of granules as controlled by granule porosity can be manipulated via different drying conditions.

Table 9: physical characterization of granules dried at different conditions.

Example 5

[00168] Section 5 : porosity vs effervescence

[00169] The dissolution rate of granules can be accelerated by employing effervescent compounds. During dissolving, the CO2 gas from an effervescent reaction can help to break down the granule structures, increasing the contact surface of materials, hence increasing the dissolution rate of granules. To compare the impact of porosity to effervescence on granule dissolution rates, effervescent compounds were blended in compact granules. The dissolution rate of the compact granules with effervescence compounds was compared with that of compact granules shown in Example 2.

[00170] Two batches of anticavity mouthwash granules containing effervescent compounds were produced using stencil printing method. One batch of granules contained encapsulated effervescence compounds citric acid and sodium bicarb with loading of effervescence at 70%, as detailed in formulation for Type 1 anticavity dry mix Al, Table 10. The other batch of granules contained mix of direct citric acid and direct sodium bicarb, as detailed in formulation for type 1 anticavity dry mix A2, Table 11. To prevent premature effervescence reaction during the printing and drying process, an anhydrous solvent-based binder was employed, as shown in Table 12.

Table 10: formulation of anticavity dry mix with encapsulated effervescence compounds.

Table 11: formulation of anticavity dry mix with direct effervescence compounds.

Table 12: formulation of anhydrous binder.

[00171] The dry mixes (Al and A2) were prepared by placing a container with dry mix in a tumbler mix for about 1 hour. The binder was prepared by mixing binder polymer and solvent in a closed jar container on a stir plate at 500 rpm for about 2 hours. When preparing the slurry for stencil print, a KitchenAid dough kneading machine was used. For print slurry of Al, dry mix Al was mixed with binder at ratio of 10/3.6 by weight. For print slurry of A2, dry mix Al was mixed with binder at ratio of 11/2.8 by weight.

[00172] A 0.016” thick stencil with hexagon pattern (hexagon side length was 3mm) was used for stencil print. The print paste was stencil printed on non-sticky PTFE coated fiberglass conveyor belt. [00173] Both prints were dried in a convection heat oven at 45 °C for 30 min with environmental humidity less than 30%. Then the granules were harvested by scraping off the belt. The obtained granules were compact in the shape of flat hexagon disks.

[00174] As shown in Table 13, the dissolution time of granules containing either type of effervescent compounds was greatly reduced from 6 min (dissolution time of granules with compact structure in Example 2) to less than 4 min. However, the dissolution time of granules with effervescence is longer than that of porous granules in Example 1 at 2 min.

[00175] Table 13: physical characterization of anticavity mouthwash granules with effervescence.

Comparing the dissolution time of compact granules with effervescent compounds (3.75 min) with the dissolution time of porous granules (2 min), the effect of effervescent reaction on dissolution rate did not surpass porosity. The compact granules with effervescent compounds (Anticavity Al and Anticavity A2) and the porous granules (22X in Example 1) packaged in compostable cellophane bags were stored in RH chamber at 37°C, 70% humidity, their physical appearance and dissolution time were monitored. Anticavity Al and Anticavity A2 granules became sticky due to wetness/moisture, and their dissolution times significantly changed more than 20% in 48 hours, while the 22X granules remained free flowing, and their dissolution time stayed the same. Therefore, the porous granules 22X are much more stable than the compact granules with effervescent compounds in terms of dissolution time.

[00176] It should be noted that there are great advantages to porosity as a means of accelerating dissolution as compared to incorporation of effervescent compounds. First, the use of effervescent reagents in dentifrice granules requires the use of strict humidity controls in manufacturing. Without careful humidity control, effervescent reagents can undergo an effervescent acid-base reaction in the presence of moisture. Depending on the extent of the reaction, this can seriously deplete the amount of effervescent reagents in the final granule. Such depleted granules may only dissolve very slowly. The entire point of using effervescent reagents is defeated. The humidity controls necessary for producing effervescent granules substantially raise manufacturing costs. Second, incorporation of effervescent reagents into granules requires the use of anhydrous solvents in preparing the print slurry. Any water in the print slurry will initiate an unwanted effervescent reaction. The use of anhydrous solvents also increases material cost.

Example 6

[00177] Section 6: porosity vs disintegrants

[00178] The dissolution rate of granules can also be enhanced by incorporating disintegrants. The swelling or wicking of disintegrants can help to break down granule structures quickly during dissolving, therefore leading to short dissolution time. To compare porosity to disintegrants in terms of granule dissolution time, disintegrants were added to the compact of Example 2. Disintegrants are classified as 1) traditional disintegrants, such as starch, alginates; and 2) superdisintegrants, such as, croscarmellose sodium, crospovidone, sodium starch glycolate, and soy polysaccharides. Superdisintegrants can function quicker and can promote disintegration at lower concentrations comparing to traditional disintegrants. Two superdisintegrants were chosen for the study in this section for their quick disintegration ability.

[00179] Two batches of compact antiseptic granules containing different superdisintegrants were produced using a jet-valving method. Croscarmellose sodium was used in the formulation detailed in Table 14 to make granules. The granules were cone shaped, with bottom circle diameter around 2mm. There was precipitation in the reconstituted solution due to the low solubility of Croscarmellose sodium. Soy polysaccharides was used in the formulation detailed in Table 15. The granules were cone shaped, with bottom circle diameter around 2mm. There was precipitation in the reconstituted solution due to the low solubility of Soy polysaccharides. The dissolution time of granules with croscarmellose sodium was about 6.5min, while the dissolution time of granules with soy polysaccharides was about 4 min.

[00180] Comparing the dissolution time of compact granules with disintegrants (6.5 min or 4 min) with the dissolution time of porous granules (2 min), the effect of disintegrants to dissolution rate did not surpass porosity.

[00181] In addition to providing a slower dissolving granule, superdisintegrants have low water solubility, undissolved disintegrants precipitate in the reconstituted solutions from their respective granules. Therefore, the utilization of disintegrants or superdisintegrants can induce turbidity or cloudiness in the reconstituted solutions, which maybe undesirable in clear solutions.

Table 14: Formulation of antiseptic emulsion with Croscarmellose Sodium as dissolving aid.

Table 15: Formulation of anticavity emulsion with Soy polysaccharide as dissolving aid.

Claims

What is claimed is:

1. A free-flowing, water-soluble dentifrice granule comprising a flavor agent, a dentifrice active and an emulsifier, wherein said granule has a porosity of from about 10% to about 70%.

2. The granule of claim 1 wherein the flavor agent is menthol, thymol, eucalyptol, methyl salicylate, wintergreen oil, myrrh oil, fennel oil, tea tree oil, peppermint oil, lemon oil, spearmint oil, mint flavor, vanilla flavor, cinnamon flavor, berry flavor (preferably strawberry, raspberry or blueberry), orange flavor, mango flavor, cherry flavor, bubblegum flavor, chocolate flavor or a combination thereof.

3. The granule of claim 2 wherein the flavor agent is peppermint oil.

4. The granule of any of claims 1 to 3 wherein flavor retention is more than 75%.

5. The granule of any of claims 1 to 4 wherein the dentifrice active is a fluoride, an essential oil, triclosan, cetylpyridinium chloride, a hydrogen peroxide source, an enzyme, chlorhexidine, strontium chloride, potassium nitrate or a vitamin.

6. The granule of claim 5 wherein the dentifrice active is an essential oil.

7. The granule of claim 6 wherein the essential oil is menthol, eucalyptol, methyl salicylate, myrrh oil, fennel oil, tea tree oil or thymol.

8. The granule of claim 7 wherein the dentifrice active is a fluoride.

9. The granule of claim 8 wherein the fluoride is amine fluoride, silver diamine fluoride, sodium monofluorophosphate, stannous fluoride or sodium monofluorophosphate.

10. The granule of claim 9 wherein the dentifrice active is a hydrogen peroxide source.

11. The granule of claim 10 wherein the hydrogen peroxide source is carbamide peroxide, sodium percarbonate, calcium peroxide, peroxydone or perbenzoic acid.

12. The granule of any of claims 1 to 11 wherein the emulsifier is lecithin, monoglyceride, diglyceride, sodium stearoyl lactylate, celluloses, starches or modified starches, gums, sucrose esters, sucroglycerides, polyglycerol esters, polyglycerol polyricinoleate, sorbitan esters, pectin, proteins or combinations thereof.

13. The granule of any of claims 1 to 12 wherein the porosity is about 10% to about 70%.

14. The granule of claim 13 wherein the porosity is about 30% to about 60%.

15. The granule of any of claims 1 to 14 further comprising a disintegrant.

16. The granule of claim 15 wherein the disintegrant is an enzyme (such as amylase, protease, cellulase, or invertase), starch and/or starch derivatives (such as sodium starch glycolate), cellulose and/or cellulose derivatives (such as croscarmellose sodium, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and microcrystalline cellulose), a hydrophilic colloidal substance (such as alginate, alginic acid NF), natural gums (such as guar gum, xantham gum, locust bean gum), crosslinked polyvinylpyrrolidone, soy polysaccharides or combinations thereof.

17. The granule of any of claims 1 to 16 further comprising a surfactant.

18. The granule of claim 17 wherein the surfactant is sodium lauryl sulfate, polysorbate, poloxamers, sodium coconut monoglycerides sulfonate, glycerol fatty acid ester, propylene glycol fatty acid ester, polyethylene glycol (PEG), sorbitan fatty acid ester, sucrose ester, taurine, sarcosine, or combinations thereof.

19. The granule of any of claims 1 to 18 further comprising an effervescent agent.

20. The granule of claim 19 wherein the effervescent agent is a bicarbonate salt or carbonate salt such as sodium carbonate, sodium bicarbonate, sodium percarbonate, potassium carbonate, potassium bicarbonate or a combination thereof.

21. The granule of any of claims 1 to 20 further comprising an effervescent activator.

22. The granule of claim 20 wherein the effervescent activator is citric acid, ascorbic acid, malic acid, fumaric acid, tartaric acid, succinic acid, adipic acid, pyruvic acid, oxaloacetic acid, maleic acid, alpha-ketoglutaric acid, alginic acid, amino acids, aconitic acid, lactic acid, and acid salt such as monosodium citrate, disodium citrate, or a combination thereof.

23. The granule of any of claims 1 to 22 wherein said granule dissolves in water at 23°C ± 1.0°C in less than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 minute.

24. A method for producing a free-flowing, water-soluble dentifrice granule having a porosity of from about 10% to about 70%, said method comprising the steps of:

(a) dispensing discrete droplets of a slurry comprising a flavor agent, a dentifrice active and an emulsifier onto a non-stick surface;

(b) drying the dispensed droplets of (a) to produce the free-flowing, water-soluble dentifrice granule having the porosity of from about 10% to about 70%.

25. The method of claim 24 wherein the flavor agent is menthol, thymol, eucalyptol, methyl salicylate, wintergreen oil, myrrh oil, fennel oil, tea tree oil, peppermint oil, lemon oil, spearmint oil, mint flavor, vanilla flavor, cinnamon flavor, berry flavor (preferably strawberry, raspberry or blueberry), orange flavor, mango flavor, cherry flavor, bubblegum flavor, chocolate flavor or a combination thereof.

26. The method of claim 25 wherein the flavor agent is peppermint oil.

27. The method of any of claims 24 to 26 wherein the granule has flavor retention of more than 75%.

28. The method of any of claims 24 to 27 wherein the dentifrice active is a fluoride, an essential oil, triclosan, cetylpyridinium chloride, a hydrogen peroxide source, an enzyme, chlorhexidine, strontium chloride, potassium nitrate or a vitamin.

29. The method of claim 28 wherein the dentifrice active is an essential oil.

30. The method of claim 29 wherein the essential oil is menthol, eucalyptol, methyl salicylate, myrrh oil, fennel oil, tea tree oil or thymol.

31. The method of claim 28 wherein the dentifrice active is a fluoride.

32. The method of claim 31 wherein the fluoride is amine fluoride, silver diamine fluoride, sodium monofluorophosphate, stannous fluoride or sodium monofluorophosphate.

33. The method of any of claims 24 to 28 wherein the dentifrice active is a hydrogen peroxide source.

34. The method of claim 33 wherein the hydrogen peroxide source is carbamide peroxide, sodium percarbonate, calcium peroxide, peroxydone or perbenzoic acid.

35. The method of any of claims 24 to 34 wherein the emulsifier is lecithin, monoglyceride, diglyceride, sodium stearoyl lactylate, celluloses, starches or modified starches, gums, sucrose esters, sucroglycerides, polyglycerol esters, polyglycerol polyricinoleate, sorbitan esters, pectin, proteins or combinations thereof.

36. The method of any of claims 26 to 35 wherein the porosity of the granule is about 10% to about 70%.

37. The method of claim 36 wherein the porosity is about 30% to about 60%.

38. The method of any of claims 24 to 37 wherein the slurry further comprises a disintegrant.

39. The method of claim 38 wherein the disintegrant is an enzyme (such as amylase, protease, cellulase, or invertase), starch and/or starch derivatives (such as sodium starch glycolate), cellulose and/or cellulose derivatives (such as croscarmellose sodium, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose and microcrystalline cellulose), a hydrophilic colloidal substance (such as alginate, alginic acid NF), natural gums (such as guar gum, xantham gum, locust bean gum), crosslinked polyvinylpyrrolidone, soy polysaccharides or combinations thereof.

40. The method of any of claims 24 to 39 wherein the slurry further comprises a surfactant.

41. The method of claim 40 wherein the surfactant is sodium lauryl sulfate, polysorbate, poloxamers, sodium coconut monoglycerides sulfonate, glycerol fatty acid ester, propylene glycol fatty acid ester, polyethylene glycol (PEG), sorbitan fatty acid ester, sucrose ester, taurine, sarcosine, or combinations thereof.

42. The method of any of claims 24 to 41 wherein the slurry further comprises an effervescent agent.

41. The method of claim 40 wherein the effervescent agent is a bicarbonate salt or carbonate salt such as sodium carbonate, sodium bicarbonate, sodium percarbonate, potassium carbonate, potassium bicarbonate or a combination thereof.

42. The method of any of claims 23 to 41 wherein the slurry further comprises an effervescent activator.

43. The method of claim 42 wherein the effervescent activator is citric acid, ascorbic acid, malic acid, fumaric acid, tartaric acid, succinic acid, adipic acid, pyruvic acid, oxaloacetic acid, maleic acid, alpha-ketoglutaric acid, alginic acid, amino acids, aconitic acid, lactic acid, and acid salt such as monosodium citrate, disodium citrate, or a combination thereof.

44. The method of any of claims 24 to 43 wherein said granule dissolves in water in less than 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 minute in water at 23°C ± 1.0°C.

45. The granule of any of claims 1 to 4 wherein the dentifrice active is one or more of an anticavity agent, an antimicrobial, an antiseptic agent, a tooth whitening agent, a tooth desensitizing agent, a disclosing agent, dental preventative or aesthetic enhancers.

46. The granule of claim 45 wherein the dentifrice active is an anticavity agent.

47. The granule of claim 46 wherein the anticavity agent is a fluoride, a xylitol or a remineralizer.

48. The granule of claim 47 wherein the anticavity agent is a remineralizer.

49. The granule of claim 48 wherein the remineralizer is hydroxyapatite, silver nanoparticles, calcium phosphate, casein phosphopeptide- amorphous calcium phosphate, calcium glycerophosphate, or other dentifrice designed to rehabilitate dentin or enamel.

50. The granule of claim 45 wherein the dentifrice active is an antimicrobial agent.

51. The granule of claim 50 wherein the antimicrobial agent is triclosan, an essential oil, cetylpyridinium chloride, chlorhexidine, chlorine dioxide, or aloe vera.

52. The granule of claim 5 wherein the dentifrice active is an enzyme.

53. The granule of claim 52 wherein the enzyme is one or more of papain, bromelain, tannase, or glucose oxidase.

54. The granule of claim 45 wherein the dentifrice active is a tooth desensitizing agent.

55. The granule of claim 54 wherein the tooth desensitizing agent is potassium nitrate, strontium chloride, strontium acetate, baking soda, fluorides, bonding resins, oxalate, arginine, casein phosphopeptide-amorphous calcium phosphate, calcium phosphate, calcium carbonate, gluma, or vitamins.

56. The granule of claim 45 wherein the dentifrice active is a dental preventative.

57. The granule of claim 56 wherein the dental preventative is an anti-gingivitis, antiplaque, anti-fungal agents.

58. The method of any of claims 24 to 27 wherein the dentifrice active is one or more of an anticavity agent, an antimicrobial, an antiseptic agent, a tooth whitening agent, a tooth desensitizing agent, a disclosing agent, dental preventative or aesthetic enhancers.

59. The method of claim 58 wherein the dentifrice active is an anticavity agent.

60. The method of claim 59 wherein the anticavity agent is a fluoride, a xylitol or a remineralizer.

61. The method of claim 60 wherein the anticavity agent is a remineralizer.

62. The method of claim 61 wherein the remineralizer is hydroxyapatite, silver nanoparticles, calcium phosphate, casein phosphopeptide-amorphous calcium phosphate, calcium glycerophosphate, or other dentifrice designed to rehabilitate dentin or enamel.

63. The method of claim 58 wherein the dentifrice active is an antimicrobial agent.

64. The method of claim 63 wherein the antimicrobial agent is triclosan, an essential oil, cetylpyridinium chloride, chlorhexidine, chlorine dioxide, or aloe vera.

65. The method of claim 28 wherein the dentifrice active is an enzyme.

66. The method of claim 65 wherein the enzyme is one or more of papain, bromelain, tannase, or glucose oxidase.

67. The method of claim 58 wherein the dentifrice active is a tooth desensitizing agent.

68. The method of claim 67 wherein the tooth desensitizing agent is potassium nitrate, strontium chloride, strontium acetate, baking soda, fluorides, bonding resins, oxalate, arginine, casein phosphopeptide-amorphous calcium phosphate, calcium phosphate, calcium carbonate, gluma, or vitamins.

69. The method of claim 58 wherein the dentifrice active is a dental preventative.

70. The method of claim 69 wherein the dental preventative is an anti-gingivitis, antiplaque, or anti-fungal agent.

71. The granule of claim 1 wherein the porosity is controlled by formulation parameters and processing conditions.

72. The granule of claim 14, wherein the porosity in the range of about 30% to about 60%, exhibits an improved dissolution rate and favorable friability characteristics.