WO2023173104A1 - Disques contenant des phospholipides et procédés de fabrication - Google Patents

Disques contenant des phospholipides et procédés de fabrication Download PDF

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Publication number
WO2023173104A1
WO2023173104A1 PCT/US2023/064163 US2023064163W WO2023173104A1 WO 2023173104 A1 WO2023173104 A1 WO 2023173104A1 US 2023064163 W US2023064163 W US 2023064163W WO 2023173104 A1 WO2023173104 A1 WO 2023173104A1
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WO
WIPO (PCT)
Prior art keywords
dissolvable
matrix
sheet
per
dissolvable sheet
Prior art date
Application number
PCT/US2023/064163
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English (en)
Inventor
Stephen M. PHIPPS
Michael A SCHMIDT
Caleb M. SCHMIDT
Original Assignee
Thorne Healthtech, Inc.
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Filing date
Publication date
Application filed by Thorne Healthtech, Inc. filed Critical Thorne Healthtech, Inc.
Publication of WO2023173104A1 publication Critical patent/WO2023173104A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals

Definitions

  • Dissolvable compositions comprising pharmaceuticals, nutritional supplements, other substances, and complex mixtures represent an efficient method of delivery or administration.
  • these compositions often suffer from low percentages of active ingredients, high hygroscopicity, slow/incomplete dissolution, or structural instability.
  • the present disclosure relates to solid, dissolvable matrices comprising active ingredients and excipients that release the active ingredient when added to a liquid.
  • An aspect of the present disclosure is method for manufacturing a dissolvable sheet.
  • the method comprising: mixing one or more scaffolding agents, one or more blowing agents, one or more active ingredients, one or more phospholipids, and water to form a mixture having a viscosity from 4,000 to 15,000 cP; depositing the mixture onto a surface having a predefined shape; and removing water from the deposited mixture to form a dissolvable sheet having a water content of less than 4% (w/w).
  • depositing the mixture comprises depositing the mixture onto a stencil.
  • the stencil has a fillable height of from 0.7 mm to 4.0 mm.
  • the dissolvable sheet has a thickness of between 100 microns and 3000 microns, such as between 300 microns and 3000 microns or between 500 microns and 2000 microns.
  • removing the water from the deposited mixture comprises heating the deposited mixture.
  • the deposited mixture is heated by exposure to a temperature of between 45 and 110 degrees Celsium.
  • the deposited mixture is heated for between 15 and 180 minutes.
  • depositing the mixture onto the surface comprises delivering the material via a printer with a squeegee pressure of 1-100 kgf.
  • the one or more phospholipids are selected from Phosphatidylcholine (PC), Lyso-Phosphatidylcholine (LPC), Phosphatidylinositol (PI), Phosphatidylethanolamine (PE), Lyso-Phosphatidylethanolamine (LPE), and Phosphatidic Acid (PA).
  • PC Phosphatidylcholine
  • LPC Lyso-Phosphatidylcholine
  • PI Phosphatidylinositol
  • PE Phosphatidylethanolamine
  • LPE Lyso-Phosphatidylethanolamine
  • PA Phosphatidic Acid
  • the one or more phospholipids may comprise from about 19% to about 23% Phosphatidylcholine (PC), from about 15% to about 22% Phosphatidylinositol (PI), from about 6 to about 13% Phosphatidylethanolamine (PE), and from about 2% to about 6% Phosphatidic Acid (PA).
  • the one or more phospholipids comprise fatty acid chains may be selected from Palmitic acid (C16:0), Stearic acid (C18:0), Oleic acid (C18: l), Linoleic acid (C18:2), and Linolenic acid (C18:3).
  • the the fatty acid chains may comprise from about 14% to about 18% Palmitic (C16:0), from about 3% to about 5% Stearic (C18:0), from about 12% to about 14% Oleic (C18: l), from about 62% to about 66% Linoleic (C18:2), and from about 2% to about 4% Linolenic (C18:3).
  • the dissolvable sheet comprises from about 0.01% to about 5%, (w/w) phospholipids.
  • the dissolvable sheet comprises at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%,
  • the dissolvable sheet comprises between 0.17% to 1.15% (w/w) phospholipids. In some embodiments, the dissolvable sheet comprises between 0.17% to 1.15%, between 0.20% to 0.8%, between 0.20% to 0.7%, between 0.20% to 0.60%, between 0.2% to 0.5%, between 0.2% to 0.4%, between 0.2% to 0.3%, between 0.25% to 0.7%, between 0.25% to 0.6%, between 0.25% to 0.5%, between 0.25% to 0.4%, between 0.25% to 0.3%, between 0.3% to 0.7%, between 0.3% to 0.6%, between 0.3% to 0.5%, or between 0.3% to 0.4% (w/w) phospholipids.
  • the one or more phospholipids is derived from lecithin.
  • the lecithin may be obtained from soybeans (including soybean oil), grains (e.g., com, rice, barley), peanuts (including peanut oil), wheat germ, hemp, pumpkin seed, sesame seed, rice bran, almonds, yeast, algae, plant oils (e.g., sunflower, canola, safflower, olive, coconut, rapeseed, flaxseed, sesame, and cottonseed), egg, milk, organ meat, or shellfish.
  • the lecithin is a de-oiled sunflower lecithin.
  • the sunflower lecithin is combined with avocado oil.
  • the de-oiled sunflower lecithin may comprise chemical and physical characteristics of one or more of acetone insoluble matter of at least 96%, toluene insoluble matter of at most 0.3%, moisture of at most 2%, acid value of at most 35 mg KOH/g, peroxide value of at most 10 meq/kg, and particle size in which 100% of particles pass through 60 mesh.
  • the dissolvable sheet comprises from about 0.1% to about 10% (w/w) lecithin.
  • the dissolvable sheet comprises at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%,
  • the dissolvable sheet comprises between 0.17% to 1.15% (w/w) lecithin. In some embodiments, the dissolvable sheet comprises between 0.17% to 1.15%, between 0.20% to 0.8%, between 0.20% to 0.7%, between 0.20% to 0.60%, between 0.2% to 0.5%, between 0.2% to 0.4%, between 0.2% to 0.3%, between 0.25% to 0.7%, between 0.25% to 0.6%, between 0.25% to 0.5%, between 0.25% to 0.4%, between 0.25% to 0.3%, between 0.3% to 0.7%, between 0.3% to 0.6%, between 0.3% to 0.5%, or between 0.3% to 0.4% (w/w) lecithin.
  • the dissolvable sheet comprises about 10 mg lecithin per 1.4 grams of dissolvable sheet. In some embodiments, the dissolvable sheet comprises between 5 mg and 10 mg lecithin per 1.8 grams of dissolvable sheet.
  • the dissolvable sheet has a dry weight from about 1 gram to about 2 grams, e.g., about 1.4 grams or 1.8 grams.
  • the active ingredient is or comprises a pharmaceutical composition; a nutraceutical composition; a plant extract, an animal extract, or a fungal extract; a prebiotic; or a sleep enhancer.
  • the active ingredient is or comprises blueberry powder, green tea decaffeinated extract (leaf), pomegranate polyphenol powder, Preforpro, Chamomile Extract, L-Theanine, Melatonin, Quercetin, Vitamin D3, Ascorbic Acid, Zinc Picolinate, mango extract, methyl cobalamin, 1-5-methyltetrahydrofolate, pyridoxal-5-phosphate, or riboflavin-5-phosphate sodium.
  • the active ingredient is or comprises one or more of Lutein (from Lutemax 2020 (Tagetes erecta)), Zeaxanthin (from Lutemax 2020 (Tagetes erecta)), Vitamin A (120 mcg RAE as Beta Carotene), Vitamin C (as Ascorbic Acid), Vitamin D (as Healthy Vitamin D3) (800 IU), Vitamin E (as d-Alpha Tocopherol from Mixed Tocopherols), Vitamin K2 (as MK-7), Zinc (as Zinc Bisglycuouse), Riboflavin (as Riboflavin 5' - Phosphate Sodium), Vitamin B6 (as Pyridoxal 5'-Phosphate), Folate (as L-5-Methyltetrahydrofolate), Vitamin B 12 (as Methylcobalamin), Choline (as Choline Citrate), iodine (as Potassium Iodide), Magnesium
  • the active ingredient when present, comprises Lutein in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Zeaxanthin in an amount of about 0.2 mg per 1.4 g dry dissolvable matrix, Vitamin A in an amount of about 0.12 mg per 1.4 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.4 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 0.02 mg per 1.4 g dry dissolvable matrix, Vitamin E in an amount of about 7.5 mg per 1.4 g dry dissolvable matrix, Vitamin K2 in an amount of about 0.05 mg per 1.4 g dry dissolvable matrix, Zinc in an amount of about 5 mg per 1.4 g dry dissolvable matrix, Riboflavin in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Vitamin B6 in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Folate in an amount of about 0.3 mg per 1.4 g dry dissolvable
  • the active ingredient when present, comprises Lutein in an amount of about 1 mg per 1.8 g dry dissolvable matrix, zeaxanthin in an amount of about 0.20 mg per 1.8 g dry dissolvable matrix, Vitamin A in an amount of about 1.34 mg per 1.8 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.8 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 0.02 mg per 1.8 g dry dissolvable matrix, Vitamin E in an amount of about 7.5 mg per 1.8 g dry dissolvable matrix, Vitamin K2 in an amount of about 0.05 mg per 1.8 g dry dissolvable matrix, Zinc in an amount of about 5 mg per 1.8 g dry dissolvable matrix, Riboflavin in an amount of about 1 mg per 1.8 g dry dissolvable matrix, Vitamin B6 in an amount of about 1 mg per 1.8 g dry dissolvable matrix, Folate in an amount of about 0.3 mg per 1.8 dry dissolvable
  • the one or more active ingredients are from about 0.05% to about 70% of the dissolvable sheet by weight, e.g., from about 0.05% to about 5%, from about 1% to about 30%, from about 5% to about 30%, or from about 1% to about 50% of the dissolvable sheet by weight.
  • the at least one excipient comprises powdered cellulose and/or quillaja extract.
  • the powdered cellulose is in an amount of 10-35% (w/w) and/or the quillaja extract in an amount of 0.5-10% (w/w).
  • the dissolvable sheet is 5- 10% powdered cellulose (w/w).
  • the quillaja extract is 0.5-10% (w/w) relative to the dissolvable sheet.
  • the at least one excipient may be configured for pore size/distribution modification and/or emulsifier stabilization, e.g., the excipient has a D50 of 50-150 microns.
  • the excipient comprises microcrystalline cellulose. In some cases, the microcrystalline cellulose in an amount of 5-15% (w/w).
  • the excipient comprises tapioca starch, microcrystalline cellulose, or Oat fiber.
  • the dissolvable sheet is 5-20% Oat fiber.
  • the microcrystalline cellulose in an amount of 5-15% (w/w).
  • the excipient comprises tapioca starch or Oat fiber.
  • the microcrystalline cellulose in an amount of 5-15% (w/w).
  • the at least one excipient comprises an emulsifier, e.g., the emulsifier comprises carboxymethyl cellulose (CMC) gum or gum acacia.
  • the emulsifier comprises carboxymethyl cellulose (CMC) gum or gum acacia.
  • the at least one excipient comprises a hygroscopicity modifier.
  • the hygroscopicity modifier comprises medium chain triglycerides (MCTs), e.g., the MCTs are 1-5% (w/w).
  • the at least one excipient comprises a mineral ion donor.
  • the mineral ion donor comprises a calcium salt, e.g., calcium carbonate.
  • the mineral ion donor comprises a magnesium salt, e.g., magnesium malate or magnesium citrate. The mineral ion donor in an amount of 1-10% (w/w).
  • the at least one excipient comprises a pullulan, e.g., the pullulan in an amount of 1-5% (w/w).
  • the amount of pullulan in a dissolvable sheet is less than the amount of pullulan in a dissolvable sheet that lacks one or more phospholipids.
  • the amount of pullulan in a dissolvable sheet may be from about 10% to about 15%, e.g., 13%, less than the amount of pullulan in a dissolvable sheet that lacks one or more phospholipids.
  • a phospholipid-containing matrix comprises less than 3.4% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.8% pullulan, a phospholipid-containing matrix comprises less than 3.2% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.5% pullulan, a phospholipid-containing matrix comprises less than 3.7% pullulan whereas an equivalent matrix yet lacking phospholipids comprises more than 4% pullulan, a phospholipid-containing matrix comprises less than 3.2% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.5% pullulan, a phospholipid-containing matrix comprises less than 2.1% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 2.3% pullulan.
  • the at least one excipient comprises a glycerin, e.g., the glycerin in an amount of 2-15% (w/w).
  • the at least one excipient comprises plant fibers, oils, gums, or collagen.
  • a void volume is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, or at least about 70% (v/v) relative to the dissolvable sheet.
  • a void volume is about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, or about 70% (v/v) relative to the dissolvable sheet. In some cases, the void volume is about 33% (v/v) relative to the dissolvable sheet.
  • dissolvable sheet comprises a balance of pore size, pore number, and pore distribution that provides desirable tensile strength, dissolution speed, and moisture transfer rates.
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.01 to about 0.04 mm 2
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.02 to about 0.03 mm 2
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.026 mm 2 .
  • the median pore area on the bottom surface of the dissolvable sheet is from about 0.01 to about 0.04 mm 2
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.015 to about 0.025 mm 2
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.020 mm 2 .
  • the average number of pores per area of the bottom surface of the dissolvable sheet is from about 15 to about 45 pores/mm 2
  • the average number of pores per area of the bottom surface of the dissolvable sheet is from about 25 to about 40 pores/mm 2
  • the average number of pores per area of the bottom surface of the dissolvable sheet is from about 30 to about 35 pores/mm 2
  • the average number of pores per area of the bottom surface of the dissolvable sheet is about 34 pores/mm 2 .
  • the mean pore area on the top surface of the dissolvable sheet is from about 1000 to about 6000 pm 2 . In some embodiments, the mean pore area on the top surface of the dissolvable sheet is from about 3000 to about 5000 pm 2 . In some embodiments, the mean pore area on the top surface of the dissolvable sheet is about 4500 pm 2 . In some embodiments, the median pore area on the top surface of the dissolvable sheet is from about 500 to about 2000 pm 2 . In some embodiments, the mean pore area on the top surface of the dissolvable sheet is from about 1000 to about 1500 pm 2 . In some embodiments, the mean pore area on the top surface of the dissolvable sheet is about 1280 pm 2 .
  • the average number of pores per area of the top surface of the dissolvable sheet is from about 15 to about 45 pores/mm 2 . In some embodiments, the average number of pores per area of the top surface of the dissolvable sheet is from about 30 to about 50 pores/mm 2 . In some embodiments, the average number of pores per area of the top surface of the dissolvable sheet is from about 35 to about 45 pores/mm 2 . In some embodiments, the average number of pores per area of the top surface of the dissolvable sheet is about 42 pores/mm 2 .
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 1000 to about 5000 pm 2 . In some embodiments, the mean pore area on the bottom surface of the dissolvable sheet is from about 1000 to about 3000 pm 2 . In some embodiments, the mean pore area on the bottom surface of the dissolvable sheet is about 2300 pm 2 . In some embodiments, the median pore area on the bottom surface of the dissolvable sheet is from about 100 to about 2000 pm 2 . In some embodiments, the mean pore area on the bottom surface of the dissolvable sheet is from about 100 to about 1000 pm 2 . In some embodiments, the mean pore area on the bottom surface of the dissolvable sheet is about 440 pm 2 .
  • the average number of pores per area of the bottom surface of the dissolvable sheet is from about 50 to about 150 pores/mm 2 . In some embodiments, the average number of pores per area of the bottom surface of the dissolvable sheet is from about 80 to about 120 pores/mm 2 . In some embodiments, the average number of pores per area of the bottom surface of the dissolvable sheet is about 96 pores/mm 2 .
  • the dissolvable sheet is shelf stable.
  • Another aspect of the present disclosure is dissolvable sheet formed by any herein- disclosed method.
  • a further aspect of the present disclosure is dissolvable sheet comprising one or more scaffolding agents, one or more blowing agents, one or more active ingredients, one or more phospholipids, and having a water content of less than 4% (w/w).
  • depositing the mixture comprises depositing the mixture onto a stencil, e.g., a stencil having a fillable height of from 0.7 mm to 4.0 mm.
  • the dissolvable sheet has a thickness of between 100 microns and 3000 microns, such as between 300 microns and 3000 microns or between 500 microns and 2000 microns.
  • removing the water from the deposited mixture comprises heating the deposited mixture, e.g., the deposited mixture is heated by exposure to a temperature of between 45 and 110 degrees Celsius.
  • the deposited mixture may be heated for between 15 and 180 minutes.
  • depositing the mixture onto the surface comprises delivering the material via a printer with a squeegee pressure of 1-100 kgf.
  • the one or more phospholipids are selected from Phosphatidylcholine (PC), Lyso-Phosphatidylcholine (LPC), Phosphatidylinositol (PI), Phosphatidylethanolamine (PE), Lyso-Phosphatidylethanolamine (LPE), and Phosphatidic Acid (PA).
  • PC Phosphatidylcholine
  • LPC Lyso-Phosphatidylcholine
  • PI Phosphatidylinositol
  • PE Phosphatidylethanolamine
  • LPE Lyso-Phosphatidylethanolamine
  • PA Phosphatidic Acid
  • the one or more phospholipids may comprise from about 19% to about 23% Phosphatidylcholine (PC), from about 15% to about 22% Phosphatidylinositol (PI), from about 6 to about 13% Phosphatidylethanolamine (PE), and from about 2% to about 6% Phosphatidic Acid (PA).
  • the one or more phospholipids comprise fatty acid chains may be selected from Palmitic acid (C16:0), Stearic acid (C18:0), Oleic acid (C18: l), Linoleic acid (C18:2), and Linolenic acid (C18:3).
  • the the fatty acid chains may comprise from about 14% to about 18% Palmitic (C16:0), from about 3% to about 5% Stearic (C18:0), from about 12% to about 14% Oleic (C18: l), from about 62% to about 66% Linoleic (C18:2), and from about 2% to about 4% Linolenic (C18:3).
  • the dissolvable sheet comprises from about 0.01% to about 5%, (w/w) phospholipids.
  • the dissolvable sheet comprises at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%,
  • the dissolvable sheet comprises between 0.17% to 1.15% (w/w) phospholipids. In some embodiments, the dissolvable sheet comprises between 0.17% to 1.15%, between 0.20% to 0.8%, between 0.20% to 0.7%, between 0.20% to 0.60%, between 0.2% to 0.5%, between 0.2% to 0.4%, between 0.2% to 0.3%, between 0.25% to 0.7%, between 0.25% to 0.6%, between 0.25% to 0.5%, between 0.25% to 0.4%, between 0.25% to 0.3%, between 0.3% to 0.7%, between 0.3% to 0.6%, between 0.3% to 0.5%, or between 0.3% to 0.4% (w/w) phospholipids.
  • the one or more phospholipids is derived from lecithin.
  • the lecithin may be obtained from soybeans (including soybean oil), grains (e.g., com, rice, barley), peanuts (including peanut oil), wheat germ, hemp, pumpkin seed, sesame seed, rice bran, almonds, yeast, algae, plant oils (e.g., sunflower, canola, safflower, olive, coconut, rapeseed, flaxseed, sesame, and cottonseed), egg, milk, organ meat, or shellfish.
  • the lecithin is a de-oiled sunflower lecithin.
  • the sunflower lecithin is combined with avocado oil.
  • the de-oiled sunflower lecithin may comprise chemical and physical characteristics of one or more of acetone insoluble matter of at least 96%, toluene insoluble matter of at most 0.3%, moisture of at most 2%, acid value of at most 35 mg KOH/g, peroxide value of at most 10 meq/kg, and particle size in which 100% of particles pass through 60 mesh.
  • the dissolvable sheet comprises at least 0.05%, 0.1%, 0.2%, 0.3%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, 6%, 8%, 10%, 15%, 20%, or 30%, (w/w) lecithin.
  • the dissolvable sheet comprises from about 0.1% to about 10% (w/w) lecithin. In various embodiments, the dissolvable sheet comprises at most 30% (w/w) lecithin. In various embodiments, the dissolvable sheet comprises at most 10% (w/w) lecithin.
  • the dissolvable sheet comprises at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%,
  • the dissolvable sheet comprises between 0.17% to 1.15% (w/w) lecithin. In some embodiments, the dissolvable sheet comprises between 0.17% to 1.15%, between 0.20% to 0.8%, between 0.20% to 0.7%, between 0.20% to 0.60%, between 0.2% to 0.5%, between 0.2% to 0.4%, between 0.2% to 0.3%, between 0.25% to 0.7%, between 0.25% to 0.6%, between 0.25% to 0.5%, between 0.25% to 0.4%, between 0.25% to 0.3%, between 0.3% to 0.7%, between 0.3% to 0.6%, between 0.3% to 0.5%, or between 0.3% to 0.4% (w/w) lecithin.
  • the dissolvable sheet comprises about 10 mg lecithin per 1.4 grams of dissolvable sheet. In some embodiments, the dissolvable sheet comprises between 5 mg and 10 mg lecithin per 1.8 grams of dissolvable sheet.
  • the dissolvable sheet has a dry weight from about 1 gram to about 2 grams, e.g., about 1.4 grams or about 1.8 grams.
  • the active ingredient is or comprises a pharmaceutical composition; a nutraceutical composition; a plant extract, an animal extract, or a fungal extract; a prebiotic; or a sleep enhancer.
  • the active ingredient is or comprises blueberry powder, green tea decaffeinated extract (leaf), pomegranate polyphenol powder, Preforpro, Chamomile Extract, L-Theanine, Melatonin, Quercetin, Vitamin D3, Ascorbic Acid, Zinc Picolinate, mango extract, methyl cobalamin, 1-5-methyltetrahydrofolate, pyridoxal-5-phosphate, or riboflavin-5-phosphate sodium.
  • the active ingredient is or comprises one or more of Lutein (from Lutemax 2020 (Tagetes erecta)), Zeaxanthin (from Lutemax 2020 (Tagetes erecta)), Vitamin A (120 mcg RAE as Beta Carotene), Vitamin C (as Ascorbic Acid), Vitamin D (as Healthy Vitamin D3) (800 IU), Vitamin E (as d-Alpha Tocopherol from Mixed Tocopherols), Vitamin K2 (as MK-7), Zinc (as Zinc Bisglycuouse), Riboflavin (as Riboflavin 5' - Phosphate Sodium), Vitamin B6 (as Pyridoxal 5'-Phosphate), Folate (as L-5-Methyltetrahydrofolate), Vitamin B 12 (as Methylcobalamin), Choline (as Choline Citrate), iodine (as Potassium Iodide), Magnesium
  • the active ingredient when present, comprises Lutein in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Zeaxanthin in an amount of about 0.2 mg per 1.4 g dry dissolvable matrix, Vitamin A in an amount of about 0.12 mg per 1.4 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.4 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 0.02 mg per 1.4 g dry dissolvable matrix, Vitamin E in an amount of about 7.5 mg per 1.4 g dry dissolvable matrix, Vitamin K2 in an amount of about 0.05 mg per 1.4 g dry dissolvable matrix, Zinc in an amount of about 5 mg per 1.4 g dry dissolvable matrix, Riboflavin in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Vitamin B6 in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Folate in an amount of about 0.3 mg per 1.4 g dry dissolvable
  • the active ingredient when present, comprises Lutein in an amount of about 1 mg per 1.8 g dry dissolvable matrix, zeaxanthin in an amount of about 0.20 mg per 1.8 g dry dissolvable matrix, Vitamin A in an amount of about 1.34 mg per 1.8 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.8 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 0.02 mg per 1.8 g dry dissolvable matrix, Vitamin E in an amount of about 7.5 mg per 1.8 g dry dissolvable matrix, Vitamin K2 in an amount of about 0.05 mg per 1.8 g dry dissolvable matrix, Zinc in an amount of about 5 mg per 1.8 g dry dissolvable matrix, Riboflavin in an amount of about 1 mg per 1.8 g dry dissolvable matrix, Vitamin B6 in an amount of about 1 mg per 1.8 g dry dissolvable matrix, Folate in an amount of about 0.3 mg per 1.8 dry dissolvable
  • the one or more active ingredients are from about 0.05% to about 70% of the dissolvable sheet by weight, e.g., from about 0.05% to about 5%, from about 1% to about 30%, from about 5% to about 30%, or from about 1% to about 50% of the dissolvable sheet by weight.
  • the at least one excipient comprises powdered cellulose and/or quillaja extract.
  • the powdered cellulose is in an amount of 10-35% (w/w) and/or the quillaja extract in an amount of 0.5-10% (w/w).
  • the dissolvable sheet is 5- 10% powdered cellulose (w/w).
  • the quillaja extract is 0.5-10% (w/w).
  • the at least one excipient may be configured for pore size/distribution modification and/or emulsifier stabilization, e.g., the excipient has a D50 of 50-150 microns.
  • the excipient comprises microcrystalline cellulose. In some cases, the microcrystalline cellulose in an amount of 5-15% (w/w).
  • the excipient comprises tapioca starch, microcrystalline cellulose, or Oat fiber.
  • the dissolvable sheet is 5-20% Oat fiber (w/w).
  • the microcrystalline cellulose in an amount of 5-15% (w/w).
  • the excipient comprises tapioca starch or Oat fiber.
  • the dissolvable sheet is 5-20% Oat fiber (w/w).
  • the microcrystalline cellulose in an amount of 5-15% (w/w).
  • the at least one excipient comprises an emulsifier, e.g., the emulsifier comprises carboxymethyl cellulose (CMC) gum or gum acacia.
  • the emulsifier comprises carboxymethyl cellulose (CMC) gum or gum acacia.
  • the at least one excipient comprises a hygroscopicity modifier.
  • the hygroscopicity modifier comprises medium chain triglycerides (MCTs), e.g., the MCTs are 1-5% (w/w).
  • the at least one excipient comprises a mineral ion donor.
  • the mineral ion donor comprises a calcium salt, e.g., calcium carbonate.
  • the mineral ion donor comprises a magnesium salt, e.g., magnesium malate or magnesium citrate. In some cases, the mineral ion donor in an amount of 1-10% (w/w).
  • the at least one excipient comprises a pullulan, e.g., the pullulan in an amount of 1-5% (w/w).
  • the amount of pullulan in a dissolvable sheet is less than the amount of pullulan in a dissolvable sheet that lacks one or more phospholipids.
  • the amount of pullulan in a dissolvable sheet may be from about 10% to about 15%, e.g., 13%, less than the amount of pullulan in a dissolvable sheet that lacks one or more phospholipids.
  • a phospholipid-containing matrix comprises less than 3.4% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.8% pullulan, a phospholipid-containing matrix comprises less than 3.2% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.5% pullulan, a phospholipid-containing matrix comprises less than 3.7% pullulan whereas an equivalent matrix yet lacking phospholipids comprises more than 4% pullulan, a phospholipid-containing matrix comprises less than 3.2% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.5% pullulan, a phospholipid-containing matrix comprises less than 2.1% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 2.3% pullulan.
  • the at least one excipient comprises a glycerin, e.g., the glycerin in an amount of 2-15% (w/w).
  • the at least one excipient comprises plant fibers, oils, gums, or collagen.
  • At least 80%, at least 90%, or at least 95% by mass of the dissolvable sheet dissolves in about 15 °C water in about 10 to 30 seconds without agitation.
  • a void volume is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, or at least about 70% (v/v) relative to the dissolvable sheet.
  • a void volume is about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, or about 70% (v/v) relative to the dissolvable sheet. In some cases, the void volume is about 33% (v/v) relative to the dissolvable sheet.
  • dissolvable sheet comprises a balance of pore size, pore number, and pore distribution that provides desirable tensile strength, dissolution speed, and moisture transfer rates.
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.01 to about 0.04 mm 2
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.02 to about 0.03 mm 2
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.026 mm 2 .
  • the median pore area on the bottom surface of the dissolvable sheet is from about 0.01 to about 0.04 mm 2
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.015 to about 0.025 mm 2
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 0.020 mm 2 .
  • the average number of pores per area of the bottom surface of the dissolvable sheet is from about 15 to about 45 pores/mm 2
  • the average number of pores per area of the bottom surface of the dissolvable sheet is from about 25 to about 40 pores/mm 2
  • the average number of pores per area of the bottom surface of the dissolvable sheet is from about 30 to about 35 pores/mm 2
  • the average number of pores per area of the bottom surface of the dissolvable sheet is about 34 pores/mm 2 .
  • the mean pore area on the top surface of the dissolvable sheet is from about 1000 to about 6000 pm 2 . In some embodiments, the mean pore area on the top surface of the dissolvable sheet is from about 3000 to about 5000 pm 2 . In some embodiments, the mean pore area on the top surface of the dissolvable sheet is about 4500 pm 2 . In some embodiments, the median pore area on the top surface of the dissolvable sheet is from about 500 to about 2000 pm 2 . In some embodiments, the mean pore area on the top surface of the dissolvable sheet is from about 1000 to about 1500 pm 2 . In some embodiments, the mean pore area on the top surface of the dissolvable sheet is about 1280 pm 2 .
  • the average number of pores per area of the top surface of the dissolvable sheet is from about 15 to about 45 pores/mm 2 . In some embodiments, the average number of pores per area of the top surface of the dissolvable sheet is from about 30 to about 50 pores/mm 2 . In some embodiments, the average number of pores per area of the top surface of the dissolvable sheet is from about 35 to about 45 pores/mm 2 . In some embodiments, the average number of pores per area of the top surface of the dissolvable sheet is about 42 pores/mm 2 .
  • the mean pore area on the bottom surface of the dissolvable sheet is from about 1000 to about 5000 pm 2 . In some embodiments, the mean pore area on the bottom surface of the dissolvable sheet is from about 1000 to about 3000 pm 2 . In some embodiments, the mean pore area on the bottom surface of the dissolvable sheet is about 2300 pm 2 . In some embodiments, the median pore area on the bottom surface of the dissolvable sheet is from about 100 to about 2000 pm 2 . In some embodiments, the mean pore area on the bottom surface of the dissolvable sheet is from about 100 to about 1000 pm 2 . In some embodiments, the mean pore area on the bottom surface of the dissolvable sheet is about 440 pm 2 .
  • the average number of pores per area of the bottom surface of the dissolvable sheet is from about 50 to about 150 pores/mm 2 . In some embodiments, the average number of pores per area of the bottom surface of the dissolvable sheet is from about 80 to about 120 pores/mm 2 . In some embodiments, the average number of pores per area of the bottom surface of the dissolvable sheet is about 96 pores/mm 2 .
  • the dissolvable sheet is shelf stable.
  • FIG. 1 depicts a workflow for the formulation of dissolvable compositions based on an active ingredient’s properties (water soluble, not hygroscopic active (Matrix 1), water soluble, hygroscopic active (Matrix la), lipophilic active (Matrix 2), and a lecithinized-extract active (Matrix 2a)).
  • an active ingredient water soluble, not hygroscopic active (Matrix 1), water soluble, hygroscopic active (Matrix la), lipophilic active (Matrix 2), and a lecithinized-extract active (Matrix 2a)).
  • FIGS. 2A-2C are light microscope images (lOOx) of a dissolvable matrix lacking phospholipids.
  • FIG. 2A is a top surface of a matrix lacking phospholipids, with the top surface defined as the surface exposed to the air during matrix formation and distal to a stencil’s surface.
  • FIG. 2B is the bottom surface of the matrix lacking phospholipids.
  • FIG. 2C reproduces FIG. 2B (left), showing a GNU Image Manipulation Program (GIMP) manipulation of the image in FIG. 2B.
  • GIMP GNU Image Manipulation Program
  • FIGS. 3A-3C are light microscope images (lOOx) of a herein-disclosed dissolvable matrix, i.e., a phospholipid-containing matrix.
  • FIG. 3A is a top surface of a dissolvable phospholipid-containing matrix, with the top surface defined as the surface exposed to the air during matrix formation and distal to a stencil’s surface.
  • FIG. 3B is the bottom surface of the phospholipid-containing matrix.
  • FIG. 3C reproduces FIG. 3B (left) and FIG. 3C shows a GNU Image Manipulation Program (GIMP) manipulation of the image in FIG. 3B.
  • GIMP GNU Image Manipulation Program
  • FIGS. 4A-4E are images captured from a video in which an illustrative phospholipidcontaining matrix is dissolved in water. No agitation was given to the disc in FIG. 4A to FIG. 4D; once the swelling, break, and incorporation of the suspension into the water occurred, moderate agitation assisted further dissolution (as shown in FIG. 4E).
  • FIG. 5A depicts SEM images used to calculate quantitative characteristics of the top surface of a dissolvable phospholipid-containing matrix 3 comprising multivitamins and minerals.
  • FIG. 5B depicts histograms of pore size distributions on the top surface of a dissolvable phospholipid-containing matrix 3 comprising multivitamins and minerals. Note the histograms correspond to the SEM images in FIG. 5A.
  • FIG. 5C depicts SEM images used to calculate quantitative characteristics of the top surface of a dissolvable matrix with low phospholipids comprising multivitamins and minerals.
  • FIG. 5D depicts histograms of pore size distributions on the top surface of a dissolvable matrix with low phospholipids comprising multivitamins and minerals. Note the histograms correspond to the SEM images in FIG. 5C.
  • FIG. 5E depicts SEM images used to calculate quantitative characteristics of the top surface of a dissolvable matrix with high phospholipids comprising multivitamins and minerals.
  • FIG. 5F depicts histograms of pore size distributions on the top surface of a dissolvable matrix with low phospholipids comprising multivitamins and minerals. Note the histograms correspond to the SEM images in FIG. 5E.
  • FIG. 6A depicts SEM images used to calculate quantitative characteristics of the bottom surface of a dissolvable phospholipid-containing matrix 3 comprising multivitamins and minerals.
  • FIG. 6B depicts histograms of pore size distributions on the bottom surface of a dissolvable phospholipid-containing matrix 3 comprising multivitamins and minerals. Note the histograms correspond to the SEM images in FIG. 6A.
  • FIG. 6C depicts SEM images used to calculate quantitative characteristics of the bottom surface of a dissolvable matrix with low phospholipids comprising multivitamins and minerals.
  • FIG. 6D depicts histograms of pore size distributions on the bottom surface of a dissolvable matrix with low phospholipids comprising multivitamins and minerals. Note the histograms correspond to the SEM images in FIG. 6C.
  • FIG. 6E depicts SEM images used to calculate quantitative characteristics of the top surface of a dissolvable matrix with high phospholipids comprising multivitamins and minerals.
  • FIG. 6F depicts histograms of pore size distributions on the top surface of a dissolvable matrix with low phospholipids comprising multivitamins and minerals. Note the histograms correspond to the SEM images in FIG. 6E.
  • FIGS. 7A-7C are light microscope images (100*) showing the Z-axis of dissolvable matrices.
  • FIG. 7A shows the Z-axis of a dissolvable phospholipid-containing matrix 3.
  • FIG. 7B shows the Z-axis of a dissolvable phospholipid-containing matrix with low phospholipids.
  • FIG. 7C shows the Z-axis of a dissolvable phospholipid-containing matrix with high phospholipids.
  • the present disclosure relates to solid, dissolvable matrices comprising active ingredients and excipients that release the active ingredient when added to a liquid.
  • the matrices’ formulations of the present disclosure i.e., phospholipid-containing matrices, take into consideration three dominant aspects that are desired for the finished product to perform against manufacturing forces, environmental forces, and to satisfy the end-user experience. This would then take into consideration the need to control the balance of pore size and pore distribution to ensure tensile strength, dissolution speed, and moisture transfer rates to ensure a finished product that is shelf stable and meets the needs of the end user.
  • Solid, dissolvable matrices of the present disclosure have a surprisingly advantageous balance of water solubility (which is promoted in part by a higher number and volume of pores) and tensile strength/stability of the matrix (during manufacture, transportation and storage).
  • too many or too large of pores reduces the strength of the matrix, and such a matrix may be brittle (i.e., lack flexibility) and/or fracture.
  • certain excipients described herein provide an ideal number of pores and size of pores in an matrix; however, above these certain amounts, the pores are undesirably irregular, large, and even form channels that transverse the matrix. It has been challenging to discover dissolvable matrix formulations that provide the proper balance to provide a desirable final product.
  • a matrix’s formulation including amounts and types of excipients and other ingredients, will vary depending on characteristics of its active ingredient.
  • the types and amounts of active ingredients, excipients, and other ingredients provide the matrix an architecture, comparing particular pore sizes, ranges, distribution, density, and volume, that affects the matrix’s dissolution rate and ability to load desirable amounts of active ingredient in the matrix.
  • illustrative phospholipid-containing matrices of the present disclosure include pore forming (blowing and scaffolding, respectively) quillaja and powdered cellulose as excipients; these excipients serve as a blowing agent coupled with a scaffolding agent, respectively, which promote pore formation and help create structure in the matrix.
  • phospholipids are one class of excipient that is included in each dissolvable matrix of the present disclosure.
  • the dissolvable matrices of the present disclosure provide consistent delivery of active ingredients having various characteristics to a liquid.
  • FIG. 1 illustrates methods for designing a matrix’s formulation based on characteristics of its active ingredients. Whether or not the active ingredient (or combination of more than one active ingredient) is water soluble is considered first. Agent(s) are deemed water soluble when the material dissolves in a water-based solvent and water insoluble when the material does not dissolve in a water-based solvent. In some instances, solubility in water is determined by a threshold amount of agent/mL solvent at a temperature for a given time. If the active ingredient(s) is water soluble, the next consideration is whether or not the active ingredient is hygroscopic, i.e., water absorbing or adsorbing.
  • Agent(s) are deemed water soluble when the material dissolves in a water-based solvent and water insoluble when the material does not dissolve in a water-based solvent. In some instances, solubility in water is determined by a threshold amount of agent/mL solvent at a temperature for a given time. If the active ingredient(s) is water soluble, the next
  • agent(s) are deemed hygroscopic when raw materials that pick up >5% mass at room temperature within nominal relative humidity conditions and not hygroscopic when raw materials that pick less than 5% at room temperature within nominal rh (relative humidity) conditions.
  • nominal relative humidity conditions comprise 30-50% relative humidity.
  • a hygroscopic agent picks up >5% mass when placed in an environment for one day at standard temperature and pressure in an environment with a relative humidity of 30%.
  • a non-hygroscopic agent picks up less than 5% mass at standard temperature and pressure for one day in an environment with a relative humidity of 30%.
  • the active ingredient (or combination of more than one active ingredient) is not hygroscopic, a formulation of dissolvable Matrix 1, as disclosed herein, can be used; if the active ingredient(s) is hygroscopic, a formulation of dissolvable Matrix la, as disclosed herein, can be used.
  • active ingredients or combinations of more than one active ingredient that are water insoluble, the next consideration is whether or not the active ingredient(s) is lipophilic, i.e., tends to dissolve in fats, oils, lipids, and non-polar solvents.
  • Agent(s) are deemed lipophilic when there is a notable bilayer formation within system and to which the addition of emulsifier rectifies the bilayer formation and not lipophilic when there is no notable bilayer formation within system.
  • lipophilicity is defined by a logP value. If the active ingredient(s) is lipophilic (as determined by a threshold value), a formulation of dissolvable Matrix 2, as disclosed herein, can be used.
  • the threshold value for a lipophilic agent is a logP more than 2.
  • the active ingredient(s) is not lipophilic and the active ingredient is lecithinized, i.e., a lipid-based vesicular delivery system, a formulation of dissolvable Matrix 2a, as disclosed herein, is used.
  • % are expressed as (w/w) of the dissolvable matrix, i.e., dissolvable sheet, after drying.
  • Table IB hydrophilic and lipophilic components. Certain features of the Matrices 3 useful in the phospholipid-containing matrices of the present disclosure are described in Table 1C:
  • % are expressed as (w/w) of the dissolvable matrix, i.e., dissolvable sheet, after drying.
  • the solid dissolvable matrices of the present disclosure comprise one or more active ingredients.
  • the one or more active ingredients provide a useful biological activity to a consumer; examples of such active ingredients include nutritional supplements, vitamins, minerals, drug therapeutics, botanicals, amino acids, proteins, oligopeptides, polypeptides, lipids (including but not limited to fatty acids, phospholipids, ceramides, sphingolipids, etc.), carbohydrates, polysaccharides, probiotics, and prebiotics.
  • the phospholipid-containing matrices allow for rapid preparation, by an end user and when needed/desired, of consumable liquid compositions comprising pharmaceuticals, nutritional supplements, and other substances.
  • the dissolvable matrices provide rapid dissolution and release of the one or more active ingredients in cold, cool, or room temperature liquid. This ability allows active ingredient delivery to and use of the matrices in numerous consumable beverages, e.g., juice, milk, and soda, which are normally served cold. Thereby, providing a palatable and desirable method for ingesting the one or more active ingredients.
  • the solid dissolvable matrices of the present disclosure i.e., phospholipid-containing matrices, have high mechanical stability and structural integrity (including being shelf-stable), rapidly dissolve in liquid, have predictable pore sizes and pore numbers, and low hygroscopicity. Many of these desirable properties are achieved by the choice of and amounts of excipients in a formulation; in some cases, the methods used to manufacture the dissolvable matrix helps provide the desirable properties.
  • dissolvable matrices are stable when stored for a period of time.
  • dissolvable matrices comprise a reproducible shelf life that meets a set of expected properties (e.g., industry or other standard).
  • dissolvable matrices retain function, dissolution rate, and handling properties over a period of time. In some instances, dissolvable matrices retain activity of one or more active ingredients over a period of time. In some instances, dissolvable matrices substantially retain structural integrity over a period of time. In some instances, dissolvable matrices do not substantially interact with primary packaging over a period of time. In some instances, dissolvable matrices do not substantially change moisture content over a period of time. In some instances, the period of time is at least 1 day, 5 days, 10 days, 30 days, 2 months, 6 months, 12 months, 18 months, 2 years, 3 years, or more than 3 years.
  • the period of time is no more than 1 day, 5 days, 10 days, 30 days, 2 months, 6 months, 12 months, 18 months, 2 years, 3 years, or no more than 5 years. In some instances, the period of time is 1-6, 1-12, 1-18, 1-24, 1-36, or 1-64 months. In some instances, dissolvable matrices are stored at a temperature of 0-25, 4-20, 4-15, 4-10, 0-10, -20 to 10, -20 to -4, or 1-8 degrees C.
  • a dissolvable matrix includes one or more excipients.
  • Excipients are distinct from the active ingredients in that they do not provide a useful biological activity to a consumer; instead, they help provide desirable properties, as disclosed herein, to a dissolvable matrix.
  • Various classes of excipients that are useful in the dissolvable matrices of the present disclosure include: phospholipids (such as lecithin-derived phospholipids), pore-creating excipients, pore-size modifying excipients, mineral ion/mineral ion donors, hygroscopicity modifiers, and emulsifiers.
  • Dissolvable matrices of the present disclosure comprise phospholipids, such as lecithin-derived phospholipids.
  • Lecithin and the phospholipids found therein are amphiphilic compounds (they attract both water and fatty substances and so are both hydrophilic and lipophilic) found in plant and animal products.
  • lecithins are mixtures of glycerophospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and phosphatidic acid.
  • Lecithins have low solubility in water, but are an excellent emulsifiers. Due to their amphiphilic nature, in aqueous solution, lecithin’s phospholipids can form either liposomes, bilayer sheets, micelles, or lamellar structures, depending on hydration and temperature.
  • Any source of phospholipids may be used in the dissolvable matrices of the present disclosure, i.e., phospholipid-containing matrices.
  • Any food- or pharmaceutical-grade phospholipid may be used in dissolvable matrices of the present disclosure, i.e., the phospholipid-containing matrices.
  • the phospholipids can be natural or synthetic.
  • Synthetic phospholipids with specific polar head group, fatty acid composition can be manufactured using various synthesis routes.
  • Synthetic phospholipids with the natural stereochemical configuration can be prepared from glycerol or glycero-3 -phosphocholine (GPC) derived from a plant or animal source, using acylation and enzyme catalyzed reactions.
  • GPC glycerol or glycero-3 -phosphocholine
  • Such phospholipids are sometimes referred to as semi-synthetic lipid because a portion of the molecule is derived from a natural source.
  • the phospholipids can be isolated from their natural source, e.g., lecithin, or they may be provided within their natural source, e.g., as lecithin.
  • Examples of vegan-type lecithins include lecithin obtained from soybeans (including soybean oil), grains (e.g., com, rice, barley), peanuts (including peanut oil), wheat germ, hemp, pumpkin seed, sesame seed, rice bran, almonds, yeast, algae, and plant oils (e.g., avocado, sunflower, canola, safflower, olive, coconut, rapeseed, flaxseed, sesame, adand cottonseed).
  • Non-vegan, vegetarian sources of lecithin include egg and milk.
  • Animal tissue-derived lecithin may also be used, e.g., from organ meat or shellfish. Additional lecithin sources are disclosed in Alhajj, Maria J., et al. "Lecithins from vegetable, land, and marine animal sources and their potential applications for cosmetic, food, and pharmaceutical sectors.” Cosmetics 7.4 (2020): 87; the contents of which is incorporated by reference in its entirety.
  • a commercially-available de-oiled sunflower lecithin is included in a phospholipid-containing matrix of the present disclosure.
  • An illustrative de-oiled sunflower lecithin may have the following characteristics: [0114]
  • the lecithin provides a variety of phospholipids. More specifically, the lecithin will comprise phospholipids having a range of structural characteristics at the Rl, R2 and R3 terminal positions according to the below triacylglycerol (TAG) molecule of Formula (I):
  • Fatty acids vary in their length and degree of unsaturation at each of the three stereospecific positions (sn-1, sn-2 and sn-3).
  • the boxed area represents the glycerol “backbone” of the molecule.
  • the Rl and R2 terminal positions comprise specific fatty acids of 8 - 22 carbon chains, e.g., C8, CIO, C12, C14, C16, C18, C20, or C22.
  • Rl and R2 fatty acids can be either saturated, unsaturated, or any combination thereof.
  • Unsaturated fatty acids can be comprised of 1, 2, 3, 4, 5, or 6 double bonds, including omega -3, -6, -7, and/or -9 fatty acids.
  • Examples of fatty acids bound to sn-1 and/or sn-2 include 8:0, 8: 1, 10:0, 10: 1, 12:0, 12: 1, 14:0, 14:1, 14:2, 16:0, 16:1 (®7), 18:0, 18: 1, 18:2 (®6), 18:3 (®6), 18:3 (®3), 18:4 (®3), 20:0, 20:1 (®9), 20:2 (®6), 20:3 (®6), 20:4 (®6), 20:4 (®3), 20.5 (®3), 22.0, 22.1 (roll), 22.1 (®9), 22.4 (®6), 22.5 (®6), 22.5 (®3), or 22.6 (®3), with the first number being the number of carbons, the number after the decimal point being the number of double bonds and the “®” number being the number of carbons from the carboxylic acid end to the first carbon in the double bond.
  • the R3 or polar position of Formula I often defines the type of phospholipid; as examples, when R3 is choline, the phospholipid is phosphatidylcholine; when R3 is inositol, the phospholipid is phosphatidylinositol; and when R3 is ethanolamine, the phospholipid is phosphatidylethanolamine.
  • An illustrative de-oiled sunflower lecithin includes a plurality of phospholipids. See, e.g., the World Wide Web (at) fda.report/media/145167/GRAS-Notice-GRN-939-Sunflower- Lecithin-part-l.pdf; the entire contents of which is incorporated by reference in its entirety.
  • the de-oiled lecithin may comprise the following components and at the specified percentages:
  • fatty acid ranges represent the total amount of each individual fatty acid bound to the phospholipids irrespective of the individual phospholipid molecular form.
  • the fatty acid percentages shown represent the percentage of a specified fatty acid bound to phospholipids and yielded upon hydrolysis of the phospholipids in the de-oiled lecithin.
  • the phospholipid percentages shown represent the percentage of a specified phospholipid relative to the total amount of phospholipids in the de-oiled lecithin.
  • each fatty acid listed in the left columns is included in one or more phospholipid of the right columns.
  • the term “conforms to standard” represent a variable amount of the specific phospholipid that may be present in a de-oiled lecithin.
  • the de-oiled lecithin is sunflower de-oiled lecithin.
  • the sunflower de-oiled lecithin is combined with avocado oil or some other oil that is principally composed of fatty acids of greater than 16 carbons in length.
  • the combination of lecithin with avocado oil or some other oil is princiapply composed of fatty acids of greater than 17 carbons in length may protect an active ingredient (e.g., DHA) from oxidative damage.
  • a “de-oiled” lecithin has its free fatty acids and triglycerides removed.
  • the de-oiled lecithin also is enriched in phospholipids. De-oiled has enhanced dispersion in water relative to is corresponding natural lecithin. De-oiled lecithin acts as an emulsifier, wetting agent, antioxidant, surfactant, dispersant, viscosity modifier, and lubricant.
  • a “phospholipid-containing matrices of the disclosure”, “herein-disclosed dissolvable matrix”, “dissolvable matrix of the present disclosure” and the like comprises phospholipids, such as lecithin-derived phospholipids, whereas a “matrix lacking phospholipids” lacks phospholipids, such as lecithin-derived phospholipids.
  • a dissolvable matrix of the present disclosure can comprise from about 0.01% to about 5% (w/w) phospholipids, such as lecithin-derived phospholipids.
  • the dissolvable matrix can comprise about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, or about 1.00% (w/w) phospholipids, such as lecithin-derived phospholipids.
  • a dissolvable matrix of the present disclosure can comprise about 1.10%, 1.20%, 1.30%, 1.40%, 1.50%,
  • a dissolvable matrix of the present disclosure can comprise at least about 0.01%, at least about 0.02%, at least about 0.03%, at least about 0.04%, at least about 0.05%, at least about 0.06%, at least about 0.07%, at least about 0.08%, at least about 0.09%, at least about 0.10%, at least about 0.20%, at least about 0.30%, at least about 0.40%, at least about 0.50%, at least about 0.60%, at least about 0.70%, at least about 0.80%, at least about 0.90%, at least about or about 1.00% (w/w) phospholipids, such as lecithin-derived phospholipids.
  • a dissolvable matrix of the present disclosure can comprise at least about 1.10%, at least about 1.20%, at least about 1.30%, at least about 1.40%, at least about 1.50%, at least about 1.60%, at least about 1.70%, at least about 1.80%, at least about 1.90%, at least about 2.00%, at least about 2.10%, at least about 2.20%, at least about 2.30%, at least about 2.40%, at least about 2.50%, at least about 2.60%, at least about 2.70%, at least about 2.80%, at least about 2.90%, at least about 3.00%, at least about 3.10%, at least about 3.20%, at least about 3.30%, at least about 3.40%, at least about 3.50%, at least about 3.60%, at least about 3.70%, at least about 3.80%, at least about 3.90%, at least about 4.00%, at least about 4.10%, at least about 4.20%, at least about 4.30%, at least about 4.40%, at least about 4.50%, at least about
  • a dissolvable matrix of the present disclosure can comprise no more than 0.01%, no more than 0.02%, no more than 0.03%, no more than 0.04%, no more than 0.05%, no more than 0.06%, no more than 0.07%, no more than 0.08%, no more than 0.09%, no more than 0.10%, no more than 0.20%, no more than 0.30%, no more than 0.40%, no more than 0.50%, no more than 0.60%, no more than 0.70%, no more than 0.80%, no more than 0.90%, no more than or about 1.00% (w/w) phospholipids, such as lecithin-derived phospholipids.
  • a dissolvable matrix of the present disclosure can comprise no more than 1.10%, no more than 1.20%, no more than 1.30%, no more than 1.40%, no more than 1.50%, no more than 1.60%, no more than 1.70%, no more than 1.80%, no more than 1.90%, no more than 2.00%, no more than 2.10%, no more than 2.20%, no more than 2.30%, no more than 2.40%, no more than 2.50%, no more than 2.60%, no more than 2.70%, no more than 2.80%, no more than 2.90%, no more than 3.00%, no more than 3.10%, no more than 3.20%, no more than 3.30%, no more than 3.40%, no more than 3.50%, no more than 3.60%, no more than 3.70%, no more than 3.80%, no more than 3.90%, no more than 4.00%, no more than 4.10%, no more than 4.20%, no more than 4.30%, no more than 4.40%, no more than 4.50%, no more than
  • lecithin-derived phospholipids may be present in a dissolvable matrix in an amount that is between 0.01% and 4%, between 0.01% and 3%, between 0.01% and 2%, between 0.01% and 1%, between 0.01% and 0.5%, between 0.02% and 3%, between 0.02% and 2%, between 0.02% and 1%, between 0.02% and 1.5%, between 0.02% and 0.5%, between 0.1% and 4%, between 0.1% and 3%, between 0.1% and 2%, between 0.1% and 1.5%, between 0.1% and 1.15%, between 0.17% and 4%, between 0.17% and 3%, between 0.17% and 2%, between 0.17% and 1.5%, between 0.17% and 1.15%, between 0.20% and 0.8%, between 0.20% and 0.7%, between 0.20% and 0.6%, between 0.20% and 0.5%, between 0.2% and 0.4%, between 0.2% and 0.3%, between 0.25% and 0.7%, between 0.25% and 0.6%, between 0.25% and 0.2% and 0.3%
  • a dissolvable matrix i.e., dissolvable sheet, which has a dry weight of between 1 gram to 2 grams, such as about 1.4 g or about 1.8 g, comprises from about 1 mg to about 20 mg of phospholipids.
  • the matrix may comprise about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, or about 20 mg of phospholipids.
  • the matrix may comprise at least about 1 mg, at least about 2 mg, at least about 3 mg, at least about 4 mg, at least about 5 mg, at least about 6 mg, at least about 7 mg, at least about 8 mg, at least about 9 mg, at least about 10 mg, at least about 11 mg, at least about 12 mg, at least about 13 mg, at least about 14 mg, at least about 15 mg, at least about 16 mg, at least about 17 mg, at least about 18 mg, at least about 19 mg, or at least about 20 mg of phospholipids.
  • the matrix may comprise no more than about 1 mg, no more than about 2 mg, no more than about 3 mg, no more than about 4 mg, no more than about 5 mg, no more than about 6 mg, no more than about 7 mg, no more than about 8 mg, no more than about 9 mg, no more than about 10 mg, no more than about 11 mg, no more than about 12 mg, no more than about 13 mg, no more than about 14 mg, no more than about 15 mg, no more than about 16 mg, no more than about 17 mg, no more than about 18 mg, no more than about 19 mg, or no more than about 20 mg of phospholipids.
  • the dissolvable matrix can comprise between about 1-20 mg, 2-15 mg, 5-10 mg, 10-20 mg, 10-15 mg, 15-20 mg, 1-15 mg, or 5-15 mg of phospholipids and any range therebetween.
  • Dissolvable sheets having greater or lesser weights (relative to the above-mentioned 1.4 grams or 1.8 grams) will have relatively greater amounts of phospholipids or relatively lesser amounts of phospholipids, respectively.
  • a dissolvable matrix can comprise at least 0.1% to 10% (w/w) lecithin.
  • the dissolvable matrix of the present disclosure can comprise about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, or about 1.00% (w/w) phospholipids, such as lecithin-derived phospholipids.
  • a dissolvable matrix of the present disclosure can comprise about 1.10%, 1.20%, 1.30%, 1.40%, 1.50%, 1.60%, 1.70%, 1.80%, 1.90%, 2.00%, 2.10%, 2.20%, 2.30%,
  • the dissolvable matrix of the present disclosure can comprise at least about 0.10%, at least about 0.20%, at least about 0.30%, at least about 0.40%, at least about 0.50%, at least about 0.60%, at least about 0.70%, at least about 0.80%, at least about 0.90%, or at least about 1.00% (w/w) lecithin.
  • a dissolvable matrix of the present disclosure can comprise at least about 1.10%, at least about 1.20%, at least about 1.30%, at least about 1.40%, at least about 1.50%, at least about 1.60%, at least about 1.70%, at least about 1.80%, at least about 1.90%, at least about 2.00%, at least about 2.10%, at least about 2.20%, at least about 2.30%, at least about 2.40%, at least about 2.50%, at least about 2.60%, at least about 2.70%, at least about 2.80%, at least about 2.90%, at least about 3.00%, at least about 3.10%, at least about 3.20%, at least about 3.30%, at least about 3.40%, at least about 3.50%, at least about 3.60%, at least about 3.70%, at least about 3.80%, at least about 3.90%, at least about 4.00%, at least about 4.10%, at least about 4.20%, at least about 4.30%, at least about 4.40%, at least about 4.50%, at least about
  • a dissolvable matrix of the present disclosure can comprise at least about 6.10%, at least about 6.20%, at least about 6.30%, at least about 6.40%, at least about 6.50%, at least about 6.60%, at least about 6.70%, at least about 6.80%, at least about 6.90%, at least about 7.00%, at least about 7.10%, at least about 7.20%, at least about 7.30%, at least about 7.40%, at least about 7.50%, at least about 7.60%, at least about 7.70%, at least about 7.80%, at least about 7.90%, at least about 8.00%, at least about 8.10%, at least about 8.20%, at least about 8.30%, at least about 8.40%, at least about 8.50%, at least about 8.60%, at least about 8.70%, at least about 8.80%, at least about 8.90%, at least about 9.00%, at least about 9.10%, at least about 9.20%, at least about 9.30%, at least about 9.40%, at least about 9.50%, at
  • a dissolvable matrix of the present disclosure can comprise no more than about 0.10%, no more than about 0.20%, no more than about 0.30%, no more than about 0.40%, no more than about 0.50%, no more than about 0.60%, no more than about 0.70%, no more than about 0.80%, no more than about 0.90%, or no more than about 1.00% (w/w) lecithin.
  • a dissolvable matrix of the present disclosure can comprise no more than about 1.10%, no more than about 1.20%, no more than about 1.30%, no more than about 1.40%, no more than about 1.50%, no more than about 1.60%, no more than about 1.70%, no more than about 1.80%, no more than about 1.90%, no more than about 2.00%, no more than about 2.10%, no more than about 2.20%, no more than about 2.30%, no more than about 2.40%, no more than about 2.50%, no more than about 2.60%, no more than about 2.70%, no more than about 2.80%, no more than about 2.90%, no more than about 3.00%, no more than about 3.10%, no more than about 3.20%, no more than about 3.30%, no more than about 3.40%, no more than about 3.50%, no more than about 3.60%, no more than about 3.70%, no more than about 3.80%, no more than about 3.90%, no more than about 4.00%, no more than about 4.10%, no
  • a dissolvable matrix of the present disclosure can comprise no more than about 6.10%, no more than about 6.20%, no more than about 6.30%, no more than about 6.40%, no more than about 6.50%, no more than about 6.60%, no more than about 6.70%, no more than about 6.80%, no more than about 6.90%, no more than about 7.00%, no more than about 7.10%, no more than about 7.20%, no more than about 7.30%, no more than about 7.40%, no more than about 7.50%, no more than about 7.60%, no more than about 7.70%, no more than about 7.80%, no more than about 7.90%, no more than about 8.00%, no more than about 8.10%, no more than about 8.20%, no more than about 8.30%, no more than about 8.40%, no more than about 8.50%, no more than about 8.60%, no more than about 8.70%, no more than about 8.80%, no more than about 8.90%, no more than about 9.00%, no more than about 9.10
  • a dissolvable matrix of the present disclosure can comprise ranges of about 0.1 -0.5%, 0.1-0.3%, 0.1-0.2%, 0.1-0.3%, 0.17-0.3%, 0.17-0.4%, 0.17-0.5% 0.17-0.6%, 0.17-0.7%, 0.2-0.3%, 0.2-0.4%, 0.2-0.5%, 0.25-0.3%, 0.25-0.4%, 0.25-0.5%, 0.25-0.6%, 0.25- 0.7%, 0.3-0.6%, 0.5-1%, 0.5-2%, 0.
  • a dissolvable matrix of the present disclosure can comprise ranges of about 1.0%-2.0%, 1.0%-3.0%, 1.0%-4.0%, 1.0%-5.0%, 1.0%-6.0%, 1.0%- 7.0%, 1.0%-8.0%, 1.0%-9.0%, 1.0%-10%, 2.0%-3.0%, 2.0%-4.0%, 2.0%-5.0%, 2.0%-6.0%, 2.0%-7.0%, 2.0%-8.0%, 2.0%-9.0%, 2.0%-10%, 3.0%-4.0%, 3.0%-5.0%, 3.0%-6.0%, 3.0%- 7.0%, 3.0%-8.0%, 3.0%-9.0%, 3.0%-10%, 4.0%-5.0%, 4.0%-6.0%, 4.0%-7.0%, 4.0%-8.0%, 4.0%-9.0%, 4.0%-10%, 5.0%-6.0%, 5.0%-7.0%, 5.0%-8.0%, 5.0%-9.0%, 5.0%-10%, 6.0%- 7.0%, 6.0%-8.0%, 6.0%-9.0%, 6.0%-10%, 6.0%- 7.0%, 6.0%-8.0%
  • dissolvable sheet which has a dry weight of about 1.4 g or 1.8 g, comprises from about 5 mg to about 30 mg of lecithin.
  • about the matrix may comprise about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, about 10 mg, about 11 mg, about 12 mg, about 13 mg, about 14 mg, about 15 mg, about 16 mg, about 17 mg, about 18 mg, about 19 mg, about 20 mg, about 21 mg, about 22 mg, about 23 mg, about 24 mg, about 25 mg, about 26 mg, about 27 mg, about 28 mg, about 29 mg, about or 30 mg lecithin.
  • at least about the matrix may comprise at least about 5 mg, at least about
  • no more than about the matrix may comprise no more than about 5 mg, no more than about 6 mg, no more than about
  • the dissolvable matrix can comprise between about 1-30 mg, 2-25 mg, 5-25 mg, 5-20 mg, 5-10 mg, 10-25 mg, 10-20 mg, 15-20 mg, 15-25 mg, or 20-25 mg of lecithin.
  • Dissolvable sheets having greater or lesser weights (relative to the above-mentioned 1.4 grams or 1.8 grams) will have relatively greater amounts of lecithin or relatively lesser amounts of lecithin, respectively.
  • Some useful excipients regulate pore creation examples include but are not limited to, scaffolding agents (e.g., powdered cellulose), and blowing agents (e.g., a saponin, quillaja extract powder (e.g., from Quillaja saponaria), Yucca schidigera, agar, citric acid plus bicarbonate, azodicarbonamide, or other soaps/amphiphilic agents).
  • scaffolding agents e.g., powdered cellulose
  • blowing agents e.g., a saponin, quillaja extract powder (e.g., from Quillaja saponaria), Yucca schidigera, agar, citric acid plus bicarbonate, azodicarbonamide, or other soaps/amphiphilic agents.
  • pore-creating excipients comprising an acid and a base (organic or mineral) are combined to produce a gas which contributes to pore creation.
  • a porecreating excipient comprises a soap which traps air or other gases in the dissolvable matrix.
  • a dissolvable matrix comprises a plurality of pores.
  • a dissolvable matrix comprises one or more of a scaffolding agent, a blowing agent, and an active ingredient.
  • a dissolvable matrix can comprise at least 1%, 2%, 5%, 8%, 10%, 15%, 20%, or 30%, (w/w) of one or more pore-creating excipients relative to the entire dissolvable matrix, when in the condition provided to a user, e.g., in its shelf stable form and not the w/w in a formulation prior to the final product.
  • a dissolvable matrix comprises at least 1%, 2%, 5%, 8%, 10%, 15%, 20%, or 30%, (w/w) of one or more pore-creating excipients relative to the dissolvable matrix, not including the mass of the one or more active ingredients.
  • the dissolvable matrix can comprise between about 1-30%, 2-25%, 5-25%, 10- 25%, 10-20%, 15-20%, 15-25%, or 20-25% (w/w) of one or more pore-creating excipients; or about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% (w/w) of each pore-creating excipient in the one or more pore-creating excipients.
  • a dissolvable matrix comprises at least 1%, 2%, 5%, 8%, 10%, 15%, 20%, or 30%, (w/w) of one or more blowing agent excipients relative to the dissolvable matrix, not including the mass of the one or more active ingredients.
  • the dissolvable matrix can comprise between about 1-30%, 2-25%, 5-25%, 10-25%, 10-20%, 15-20%, 15-25%, or 20-25% (w/w) of one or more blowing agent excipients; or about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% (w/w) of each blowing agent excipient in the one or more blowing agent excipients.
  • a dissolvable matrix comprises at least 1%, 2%, 5%, 8%, 10%, 15%, 20%, or 30%, (w/w) of one or more scaffolding excipients relative to the dissolvable matrix, not including the mass of the one or more active ingredients.
  • the dissolvable matrix can comprise between about 1-30%, 2-25%, 5-25%, 10-25%, 10-20%, 15-20%, 15-25%, or 20-25% (w/w) of one or more scaffolding excipients; or about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% (w/w) of each scaffolding excipient in the one or more scaffolding excipients.
  • Quillaja extract powder can act like an emulsifier as well as pore-creating excipient, since it is saponin rich. Therefore, in a matrix comprising a water insoluble active ingredient(s), quillaja extract powder can be present in a higher amount, e.g., over 6% (w/w), whereas in a matrix comprising water soluble active ingredient(s), quillaja extract powder is present in about 1-2% (w/w) each relative to the entire dissolvable matrix, with respect to the final dissolvable matrix.
  • a dissolvable matrix can comprise between 1-6%, 2-6%, 3-6%, 4-6%, 5-6%, 2-3%, 2-4%, 2-5%, 3-4%, 3-5% or 4-5% (w/w) relative to the entire dissolvable matrix.
  • quillaja extract comprises saponins. In some instances, quillaja extract comprises at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or at least 90% saponins (w/w).
  • quillaja extract comprises 10-95%, 10-90%, 10-80%, 10- 70%, 10-60%, 10-50%, 10-25%, 20%-90%, 20%-70%, 20%-50%, 30%-75%, 40%-85%, 40%- 90%, 50%-75%, 50%-85%, 60%-90%, or 70%-95% saponins (w/w). In some instances, quillaja extract comprises at least 20% saponins (w/w). [0127] The pore-creating excipient can comprise saponins.
  • a dissolvable matrix comprises 0.1-5%, 0.1-3%, 0.1-2%, 0.1-1%, 0.2-2%, 0.2-1%, 0.3-3%, 0.5-2%, 0.5-3%, 0.5-9%, 0.5-8%, 0.5-7%, 0.5-6%, 0.5-5%, 1-2.5%, 2%-9%, 2%-7%, 2%-10%, 5-10%, 3%- 20%, 5-40%, or 10-40% saponins (w/w).
  • a dissolvable matrix comprises at least 0.05%, 0.1%, 0.2%, 0.3%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, 6%, 8%, or at least 10% (w/w) saponins.
  • the pore-creating excipient can comprise powdered cellulose and quillaja extract powder.
  • the amount of powdered cellulose can vary from about 5% to about 30% (w/w) or from 8% to about 30% (w/w) and the amount of quillaja extract powder can vary from about 1% to about 7% (w/w); each with respect to the final dissolvable matrix.
  • the amount of powdered cellulose can be about 5%, 5.5%, 6.0%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%, 12%, 12.5%, 13%, 13.5%, 14%, 14.5%, 15%, 15.5%, 16%, 16.5%, 17%, 17.5%, 18%, 18.5%, 19%, 19.5%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% (w/w) and the amount of quillaja extract powder can be about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3%, 3.2%, 3.4%, 3.6%, 3.8%, 4%, 4.2%, 4.4%, 4.6%, 4.8%, 5%, 5.2%, 5.4%, 5.6%, 5.8%,
  • a formulation of dissolvable Matrix 1, as disclosed herein, can comprise between about 16% and about 33% (w/w) of the pore-creating excipient relative to the entire dissolvable matrix.
  • the pore-creating excipients may comprise about 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, or 33% (w/w) with respect to the final dissolvable matrix.
  • the pore-creating excipient can comprise powdered cellulose and quillaja extract powder.
  • the amount of powdered cellulose can vary from about 15% to about 30% (w/w) and the amount of quillaja extract powder can vary from about 1% to about 3% (w/w); each with respect to the final dissolvable matrix.
  • the amount of powdered cellulose can be about 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% (w/w) and the amount of quillaja extract powder can be about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, or 3% (w/w).
  • a formulation of dissolvable Matrix 1 comprises about 17.73% powdered cellulose and about 1.48% quillaja extract powder (w/w), about 17.23% powdered cellulose and about 1.44% quillaja extract powder (w/w); about 18.83% powdered cellulose and about 1.57% quillaja extract powder (w/w), about 22.73% powdered cellulose and about 1.42% quillaja extract powder (w/w), each relative to the final dissolvable matrix.
  • a formulation of dissolvable Matrix la can comprise between about 16% and about 33% (w/w) of the pore-creating excipient relative to the entire dissolvable matrix.
  • the pore-creating excipients may comprise about 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, or 33% (w/w) with respect to the final dissolvable matrix.
  • the pore-creating excipient can comprise powdered cellulose and quillaja extract powder.
  • the amount of powdered cellulose can vary from about 17% to about 20% (w/w) and the amount of quillaja extract powder can vary from about 1% to about 3% (w/w); each with respect to the final dissolvable matrix.
  • the amount of powdered cellulose can be about 17%, 17.2%, 17.4%, 17.6%, 17.8%, 18%, 18.2%, 18.4%, 18.6%, 18.8%, 19%, 19.2%, 19.4%, 19.6%, 19.8%, or 20% (w/w) and the amount of quillaja extract powder can be about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, or 3% (w/w).
  • a formulation of dissolvable Matrix la comprises about 17.73% powdered cellulose and about 1.48% quillaja extract powder (w/w), about 17.23% powdered cellulose and about 1.44% quillaja extract powder (w/w), or about 18.83% powdered cellulose and about 1.57% quillaja extract powder (w/w), each relative to the final dissolvable matrix.
  • a formulation of dissolvable Matrix 2, as disclosed herein, can comprise between about 15% and about 30% (w/w) of the pore-creating excipient relative to the entire dissolvable matrix.
  • the pore-creating excipients may comprise about 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% (w/w) with respect to the final dissolvable matrix.
  • the pore-creating excipient can comprise powdered cellulose and quillaja extract powder.
  • the amount of powdered cellulose can vary from about 12% to about 20% (w/w) and the amount of quillaja extract powder can vary from about 3% to about 8% (w/w); each with respect to the final dissolvable matrix.
  • the amount of powdered cellulose can be about 14%, 14.2%, 14.4%, 14.6%, 14.8%, 15%, 15.2%, 15.4%, 15.6%, 15.8%, 16%, 16.2%, 16.4%, 16.6%, 16.8%, 17%, 17.2%, 17.4%, 17.6%, 17.8%, or 18% (w/w) and the amount of quillaja extract powder can be about 5%, 5.2%, 5.4%, 5.6%, 5.8%, 6%, 6.2%, 6.4%, 6.6%, 6.8%, or 7% (w/w).
  • a formulation of dissolvable Matrix 2 comprises about 15.81% powdered cellulose and about 6.32% quillaja extract powder (w/w) relative to the final dissolvable matrix.
  • a formulation of dissolvable Matrix 2a can comprise between about 15% and about 30% (w/w) of the pore-creating excipient relative to the entire dissolvable matrix.
  • the pore-creating excipients may comprise about 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% (w/w) with respect to the final dissolvable matrix.
  • the pore-creating excipient can comprise powdered cellulose and quillaja extract powder.
  • the amount of powdered cellulose can vary from about 12% to about 20% (w/w) and the amount of quillaja extract powder can vary from about 2% to about 7% (w/w); each with respect to the final dissolvable matrix.
  • the amount of powdered cellulose can be about 15%, 15.2%, 15.4%, 15.6%, 15.8%, 16%, 16.2%, 16.4%, 16.6%, 16.8%, 17%, 17.2%, 17.4%, 17.6%, 17.8%, or 18% (w/w) and the amount of quillaja extract powder can be about 2%, 2.2%, 2.4%, 2.6%, 2.8%, 3%, 3.2%, 3.4%, 3.6%, 3.8%, 4%, 4.2%, 4.4%, 4.6%, 4.8%, 5%, 5.2%, 5.4%, 5.6%, 5.8%, or 6% (w/w).
  • a formulation of dissolvable Matrix 2a comprises about 16.71% powdered cellulose and about 4.18% quillaja extract powder (w/w) relative to the final dissolvable matrix.
  • a formulation e.g., a formulation of dissolvable Matrix 3
  • the pore-creating excipient can comprise powdered cellulose and quillaja extract powder.
  • the dissolvable sheet can comprise between 3% to 10% (w/w) (e.g., between 3% and about 8%) powdered cellulose and between about 3% to about 8% (w/w) quillaja extract powder.
  • a formulation of dissolvable Matrix 3 comprises about 5.61% powdered cellulose and about 4.49% quillaja extract powder (w/w) relative to the final dissolvable matrix.
  • pore size modifiers which are also capable of being emulsifier stabilizers
  • examples of pore size modifiers include but are not limited to fibers (e.g., oat fiber), cellulose or cellulose derivatives, (e.g., cellulose, microcrystalline cellulose), starches (e.g., tapioca starch), wheat bran, or lignins.
  • Such pore size modifier/emulsifier stabilizers also act as bulking agents to a dissolvable matrix.
  • pore size modifiers have different density or volume properties relative to other components in the dissolvable matrix.
  • the pore size modifier or emulsifier stabilizer has an average particle size of 10-300, 10-200, 10-100, 20-100, 40-80, 50-200, 100-200, 50-100, or 150-250 microns. In some instances, the pore size modifier or emulsifier stabilizer has a D50 (size in microns that splits the distribution of particles equally above and below a set diameter) of about 5, 10, 20, 25, 50, 75, 100, 125, 150, 200, or about 500 microns.
  • the pore size modifier or emulsifier stabilizer has a D50 (portion of particles with diameters smaller or larger than a size in microns) of 5-500, 10-200, 10-100, 5-25, 50-500, 75-125, 100-500, 200-500, 10- 500, or 50-100 microns.
  • a dissolvable matrix can comprise at least 1%, 2%, 5%, 8%, 10%, 15%, or 20% (w/w) of one or more pore-size modifying excipients relative to the entire dissolvable matrix, when in the condition provided to a user, e.g., in its shelf stable form and not the w/w in a formulation prior to the final product.
  • the dissolvable matrix can comprise between about 1-20%, 2-20%, 5-20%, 10-15%, 10-20%, or 15-20% (w/w) of one or more pore-size modifying excipients; or about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 11% (w/w) of each poresize modifying excipient in the one or more pore-size modifying excipients.
  • a formulation of dissolvable Matrix 1, as disclosed herein, can comprise between about 5% and 15% (w/w) of the pore-size modifying excipient relative to the entire dissolvable matrix.
  • the pore-creating excipients may comprise about 5%, 5.2%, 5.4%, 5.6%, 5.8%, 6%, 6.2%, 6.4%, 6.6%, 6.8%, 7%, 7.2%, 7.4%, 7.6%, 7.8%, 8%, 8.2%, 8.4%, 8.6%, 8.8%, 9%, 9.2%, 9.4%, 9.6%, 9.8%, 10%, 10.2%, 10.4%, 10.6%, 10.8%, 11%, 11.2%, 11.4%, 11.6%, 11.8%, 12%, 12.2%, 12.4%, 12.6%, 12.8%, 13%, 13.2%, 13.4%, 13.6%, 13.8%, 14%, 14.2%, 14.4%, 14.6%, 14.8%, or 15% (w/w) with respect to the final dissolvable matrix.
  • the porecreating excipient can comprise microcrystalline cellulose.
  • the amount of microcrystalline cellulose can vary from about 8% to about 13% (w/w). As examples, the amount of microcrystalline cellulose can be about 8%, 9%, 10%, 11%, 12%, or 13%.
  • a formulation of dissolvable Matrix 1 comprises about 11.37% microcrystalline cellulose (w/w), relative to the final dissolvable matrix.
  • a pore-creating excipient comprises a cellulose derivative (e.g., methylcellulose, hydroxypropyl cellulose, and carboxymethyl cellulose (CMC)).
  • CMC carboxymethyl cellulose
  • a formulation of dissolvable Matrix la can comprise between about 5% and 10% (w/w) of the pore-size modifying excipient relative to the entire dissolvable matrix.
  • the pore-creating excipients may comprise about 5%, 5.2%, 5.4%, 5.6%, 5.8%, 6%, 6.2%, 6.4%, 6.6%, 6.8%, 7%, 7.2%, 7.4%, 7.6%, 7.8%, 8%, 8.2%, 8.4%, 8.6%, 8.8%, 9%, 9.2%, 9.4%, 9.6%, 9.8%, 10% (w/w) with respect to the final dissolvable matrix.
  • the porecreating excipient can comprise microcrystalline cellulose.
  • the amount of microcrystalline cellulose can vary from about 6% to about 8% (w/w).
  • the amount of microcrystalline cellulose can be about 6%, 6.2%, 6.4%, 6.6%, 6.8%, 7%, 7.2%, 7.4%, 7.6%, 7.8%, 8% (w/w).
  • a formulation of dissolvable Matrix la comprises about 6.82%, 7.02%, or 7.45% microcrystalline cellulose (w/w), each relative to the final dissolvable matrix.
  • a formulation of dissolvable Matrix 2, as disclosed herein, can comprise between about 1% and 13% (w/w) of the pore-size modifying excipient relative to the entire dissolvable matrix.
  • the pore-size modifying excipients may comprise about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, and 13% (w/w) with respect to the final dissolvable matrix.
  • the pore-size modifying excipient can comprise a fiber, e.g., oat fiber.
  • the amount of oat fiber can vary from about 2.5% to about 4.5% (w/w) with respect to the final dissolvable matrix.
  • the amount of oat fiber can be about 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4%, 4.1%, 4.2%, 4.3%, 4.4%, or 4.5% (w/w).
  • a formulation of dissolvable Matrix 2 comprises about 3.32% oat fiber relative to the final dissolvable matrix.
  • a formulation of dissolvable Matrix 2a can comprise between about 0.5% and 2.5% (w/w) of the pore-size modifying excipient relative to the entire dissolvable matrix.
  • the pore-size modifying excipients may comprise about 0.5%, 1%, 1.5%, 2%, or 2.5% (w/w) with respect to the final dissolvable matrix.
  • the pore-size modifying excipient can comprise tapioca starch. The amount of tapioca starch can vary from about 1% to about 2% (w/w) with respect to the final dissolvable matrix.
  • the amount of tapioca starch can be about 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, or 2% (w/w).
  • a formulation of dissolvable Matrix 2a comprises about 1.19% tapioca starch (w/w) relative to the final dissolvable matrix.
  • a formulation of dissolvable Matrix 2a can comprise between about 1% and 13% (w/w) of the pore-size modifying excipient relative to the entire dissolvable matrix.
  • the pore-size modifying excipients may comprise about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, and 13% (w/w) with respect to the final dissolvable matrix.
  • the pore-size modifying excipient can comprise a fiber, (e.g., oat, brown rice, buckwheat, bulgur, millet, oatmeal, popcorn, quinoa, whole grain barley, whole-grain corn, whole oats/oatmeal, whole rye, whole wheat, rolled oats, or wild rice ).
  • the amount of fiber can vary from about 2.5% to about 4.5% (w/w) with respect to the final dissolvable matrix.
  • the amount of fiber can be about 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4%, 4.1%, 4.2%, 4.3%, 4.4%, or 4.5% (w/w).
  • the amount of oat fiber can vary from about 2.5% to about 4.5% (w/w) with respect to the final dissolvable matrix. In some instances, oat fiber is used.
  • the amount of oat fiber can be about 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4%, 4.1%, 4.2%, 4.3%, 4.4%, or 4.5% (w/w).
  • a formulation of dissolvable Matrix 2a comprises about 3.32% oat fiber relative to the final dissolvable matrix.
  • the pore-size modifying excipients may comprise about 8.5%, 9%, 9.5%, 10%, 10.5%, or 11% (w/w) with respect to the final dissolvable matrix.
  • the pore-size modifying excipient can comprise tapioca starch.
  • the amount of tapioca starch can vary from about 8% to about 10% (w/w) with respect to the final dissolvable matrix.
  • the amount of tapioca starch can be about 8%, 8.1%, 8.2%, 8.3%, 8.4%, 8.5%, 8.6%, 8.7%, 8.8%, 8.9%, 9%, 9.1%, 9.2%, 9.3%, 9.4%, 9.5%, 9.6%, 9.7%, 9.8%, 9.9%, or 10% (w/w).
  • a formulation of dissolvable Matrix 2a comprises about 9.46% tapioca starch (w/w) relative to the final dissolvable matrix.
  • a formulation e.g., a formulation of dissolvable Matrix 3
  • the pore-size modifying excipient can comprise a fiber, e.g., oat fiber.
  • the amount of oat fiber can vary between 5-10%, 5-15%, 5-20%, 10-15%, 10-20% or 15-20% (w/w) with respect to the final dissolvable matrix.
  • a formulation of dissolvable Matrix 3 comprises about 16.83% oat fiber relative to the final dissolvable matrix.
  • mineral ions or mineral ion donors.
  • mineral ion/mineral ion donors in some instances reverse solubility (i.e., increased dissolution of the mineral at lower solvent temperatures) and allow for the disruption of the surface layer to increase the disintegration potential.
  • mineral ion/mineral ion donors work synergistically with the blowing agent to produces pores.
  • a mineral ion/mineral ion donors in some instances produces a gas upon mixing.
  • Example of mineral ion donors include, but are not limited to, calcium, magnesium, potassium, sodium, iron, cobalt, zinc, copper, or manganese.
  • Such mineral ions can be present as a phosphate, a carbonate, a sulfate, an iodide, a fluoride, or other counterion.
  • a mineral ion comprises a carbonate and is mixed with an organic or inorganic acid.
  • the mineral ion comprises a carbonate and/or citrate.
  • one or more active ingredients have specific pH requirements for use in a dissolvable matrix.
  • mineral ions are used to adjust the pH when formulating a dissolvable matrix described herein.
  • a dissolvable matrix can comprise between about 0.5% and about 20% (w/v), e.g., about or at least 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% (w/w) of one or more mineral ions/mineral ion donors relative to the entire dissolvable matrix, when in the condition provided to a user, e.g., in its shelf stable form and not the w/w in a formulation prior to the final product.
  • the dissolvable matrix can comprise between about 0.5-6%, 1-5%, 1.5-4%, 2-4%, 3-5%, 4-5%, 1- 10%, 1-15%, 1-20%, 5-10%, 5-15%, 5-20%, 10-15%, 10-20% or 15-20% (w/w) of one ormore mineral ions/mineral ion donors; or about 0.25%, 0.5%, 0.8%, 1.1%, 1.4%, 1.7%, 2%, 2.3%, 2.6%, 2.9%, 3.2%, 3.5%, 3.8%, 4.1%, 4.4%, 4.7%, 5%, 5.3%, 5.6%, or 5.9% (w/w) of each mineral ions/mineral ion donors in the one or more mineral ions/mineral ion donors.
  • the relative concentration of a mineral ion/mineral ion donors may be depend on the amount of lecithin that included a matrix.
  • mineral ions in some instances e.g., calcium
  • mineral ions may disrupt film forming properties of a matrix described herein.
  • mineral ions are added to matrices comprising a lecithinized botanical extract.
  • calcium ions are added to matrices comprising lecithinized botanical extract.
  • a formulation of dissolvable Matrix 2a can comprise between about 0.8% and 5% (w/w) of the mineral ions/mineral ion donors relative to the entire dissolvable matrix.
  • the mineral ions/mineral ion donors may comprise about 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, or 5% (w/w) with respect to the final dissolvable matrix.
  • the mineral ion/mineral ion donor may be calcium carbonate.
  • the amount of calcium carbonate can vary from about 0.8% to about 3% (w/w) with respect to the final dissolvable matrix.
  • the amount of calcium carbonate can be about 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, or 3% (w/w).
  • the amount of calcium carbonate can vary from about 3.5% to about 5% (w/w) with respect to the final dissolvable matrix.
  • the amount of calcium carbonate can be about 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, or 5% (w/w).
  • formulations of dissolvable Matrix 2a comprise about 1.19% or about 4.19% calcium carbonate (w/w) each relative to the final dissolvable matrix.
  • a formulation e.g., a formulation of dissolvable Matrix 3
  • the mineral ion/mineral ion donor may comprise magnesium malate.
  • the mineral ion/mineral ion donor may comprise magnesium citrate.
  • the amount of magnesium malate is from 1% to 10% (w/w) with respect to the final dissolvable matrix.
  • the amount of magnesium citrate is from 1% to 15% (w/w) with respect to the final dissolvable matrix.
  • the amount of magnesium malate can be between 1-2%, 1-5%, 1-8%, 1-10%, 2-5%, 2-8%, 2-10%, 5-8%, 5- 10% or 8-10% (w/w) of the final dissolvable matrix.
  • the amount of magnesium citrate can be between 1-5%, 1-10%, 1-15%, 5-8%, 5-10%, 5-15% or 10-15% (w/w) of the final dissolvable matrix.
  • formulations of dissolvable Matrix 3 comprise both 5.12% magnesium malate and 8.13% magnesium citrate (w/w), each relative to the final dissolvable matrix.
  • An excipient may be a hygroscopicity modifier, designed to modulate the rate at which the matrix absorbs moisture in the air.
  • the hygroscopicity modifier comprises a hydrophilic substance.
  • the hygroscopicity modifier comprises an oil.
  • the hygroscopicity modifier comprises a vegetable oil.
  • the hygroscopicity modifier comprises an dairy-derived oil or fat.
  • the hygroscopicity modifier comprises a triglyceride.
  • a hygroscopicity modifier can comprise a triglyceride oil such as a short-chain triglyceride (SCT) oil, a medium chain triglyceride (MCT) oil (e.g., MCT oil powder), or long chain triglyceride (LCT) oil.
  • SCT short-chain triglyceride
  • MCT medium chain triglyceride
  • LCT long chain triglyceride
  • hygroscopicity modifiers herein include coconut oil, palm kernel oil, avocado oil, whole milk, and butter.
  • a hygroscopicity modifier comprises a fatty acid.
  • a hygroscopicity modifier is a C6-C12 fatty acid.
  • a hygroscopicity modifier is a C12-C18 fatty acid.
  • a dissolvable matrix can comprise at least 1%, 2%, 3%, 4%, or 5% (w/w) of one or more hygroscopicity modifiers relative to the entire dissolvable matrix, when in the condition provided to a user, e.g., in its shelf stable form and not the w/w in a formulation prior to the final product.
  • the dissolvable matrix can comprise between about 1-5%, 2-5%, 2-4%, 3- 5%, 3-4%, or 4-5% (w/w) of one or more mineral ions/mineral ion donors; or about 0.4%, 0.6%, 0.8%, 1%, 1.2%, 1.4%, 1.6%, 1.8%, 2%, 2.2%, 2.4%, 2.6%, 2.8%, 3%, 3.2%, 3.4%, 3.6%, 3.8%, 4%, 4.2%, 4.4%, 4.6%, 4.8%, or 5% (w/w) of each mineral ions/mineral ion donors in the one or more mineral ions/mineral ion donors.
  • a formulation of dissolvable Matrix 1, as disclosed herein, can comprise between about 1% and 5% (w/w) of the hygroscopicity modifiers relative to the entire dissolvable matrix.
  • the hygroscopicity modifiers may comprise about 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5% (w/w) with respect to the final dissolvable matrix.
  • the hygroscopicity modifier may be medium-chain triglyceride (MCT) oil powder.
  • MCT medium-chain triglyceride
  • the amount of MCT oil powder can be about 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4%, .2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, or 5% (w/w).
  • formulations of dissolvable Matrix 2a comprise about 4.26% MCT oil powder (w/w) each relative to the final dissolvable matrix.
  • a formulation of dissolvable Matrix la can comprise between about 1% and 5% (w/w) of the hygroscopicity modifiers relative to the entire dissolvable matrix.
  • the hygroscopicity modifiers may comprise about 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5% (w/w) with respect to the final dissolvable matrix.
  • the hygroscopicity modifier may be MCT oil powder.
  • the amount of MCT oil powder can vary from about 0.8% to about 3% (w/w) with respect to the final dissolvable matrix.
  • the amount of MCT oil powder can be about 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, or 4% (w/w).
  • formulations of dissolvable Matrix 2a comprise about 2.96% or about 3.14% MCT oil powder (w/w) each relative to the final dissolvable matrix.
  • excipients are emulsifiers.
  • emulsifier include but are not limited to carboxymethyl cellulose gum (CMC gum), mustard, soy and egg lecithin, mono- and diglycerides, polysorbates, carrageenan, guar gum, xanthan gum, gum acacia or canola oil.
  • An emulsifier can affect the inherent homogeneity of the ink, and the overall dispersion and suspension of the material within an aqueous form.
  • a formulation of dissolvable Matrix 2, as disclosed herein, can comprise between about 0.05% and 1.0% (w/w) of an emulsifier relative to the entire dissolvable matrix.
  • the emulsifier may comprise about 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, or 1% (w/w) carboxymethyl cellulose gum (CMC) gum with respect to the final dissolvable matrix.
  • the emulsifier may be CMC gum.
  • the amount of CMC gum can vary from about 0.05% to about 0.25% (w/w) with respect to the final dissolvable matrix.
  • the amount of MCT oil powder can be about 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.2%, 0.21%, 0.22%, 0.23%, 0.24%, or 0.25% (w/w).
  • a formulation of dissolvable Matrix 2 comprises about 0.16% CMC gum (w/w) relative to the final dissolvable matrix.
  • a formulation of dissolvable Matrix 2a can comprise between about 0.05% and 1.0% (w/w) of an emulsifier relative to the entire dissolvable matrix.
  • the emulsifier may comprise about 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, or 1% (w/w) carboxymethyl cellulose gum (CMC) gum with respect to the final dissolvable matrix.
  • the emulsifier may be CMC gum.
  • the amount of CMC gum can vary from about 0.05% to about 0.25% (w/w) with respect to the final dissolvable matrix.
  • the amount of MCT oil powder can be about 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19%, 0.2%, 0.21%, 0.22%, 0.23%, 0.24%, or 0.25% (w/w).
  • a formulation of dissolvable Matrix 2 comprises about 0.16% CMC gum (w/w) relative to the final dissolvable matrix.
  • Matrix 2a which includes a lecithinized-active ingredient
  • lower amounts of emulsifiers are needed in a dissolvable matrix. This is because the lecithin comprises phosphatidylcholine, which is an emulsifier.
  • a formulation e.g., a formulation of dissolvable Matrix 3
  • the emulsifier may be gum acacia.
  • the gum acacia may be present in the final dissolvable composition in an amount between 1-2%, 1-3%, 1-4%, 1-5%, 2-3%, 2-4%, 2-5%, 3-4%, 3-5% or 4-5% (w/w).
  • any of the dissolvable matrices disclosed herein may comprise an excipient that comprises a humectant.
  • Humectants can be present in 2-20% 2-15%, 2-10%, 2-5%, 3-5%, 3- 10%, 3-6%, 4-8%, 4-15%, 5-10%, 5-15%, 5-20%, 6-10%, 6-15%, 8-15%, 8-20%, 10-20%, 12- 20%, 15-20%, 15-30% (w/w) with respect to the final dissolvable matrix.
  • humectants are present in about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15% (w/w) with respect to the final dissolvable matrix.
  • a formulation of dissolvable Matrix la comprises about 3.14% humectant (w/w), a formulation of dissolvable Matrix la comprises about 4.43% humectant (w/w), a formulation of dissolvable Matrix la comprises about 5.74% humectant (w/w), a formulation of dissolvable Matrix 2 comprises about 12.65% humectant (w/w), a formulation of dissolvable Matrix 2a comprises about 7.16% humectant (w/w), and a formulation of dissolvable Matrix 3 comprises about 2.81% humectant (w/w), each relative to the final dissolvable matrix.
  • glycerin is used as an excipient.
  • Glycerin can be present in 2-20% 2-15%, 2-10%, 2-5%, 3-5%, 3-10%, 3-6%, 4-8%, 4-15%, 5-10%, 5-15%, 5-20%, 6-10%, 6-15%, 8-15%, 8-20%, 10-20%, 12-20%, 15-20%, 15-30% (w/w) with respect to the final dissolvable matrix. In some instances glycerin is present in about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15% (w/w) with respect to the final dissolvable matrix.
  • a formulation of dissolvable Matrix la comprises about 3.14% glycerin (w/w), a formulation of dissolvable Matrix la comprises about 4.43% glycerin (w/w), a formulation of dissolvable Matrix la comprises about 5.74% glycerin (w/w), a formulation of dissolvable Matrix 2 comprises about 12.65% glycerin (w/w), a formulation of dissolvable Matrix 2a comprises about 7.16% glycerin (w/w), and a formulation of dissolvable Matrix 3 comprises about 2.81% glycerin (w/w), each relative to the final dissolvable matrix.
  • humectants include but are not limited to glycerin, alpha hydroxyl acids (e.g., glycolic acid, lactic acid), sodium pyrrolidine carboxylic acid, propylene glycol, butylene glycol, hyaluronic acid, urea, panthenol, aluminum lactate, sodium lactate, gelatin, sorbitol, or honey.
  • alpha hydroxyl acids e.g., glycolic acid, lactic acid
  • sodium pyrrolidine carboxylic acid e.g., glycolic acid, lactic acid
  • propylene glycol e.g., butylene glycol, hyaluronic acid, urea
  • panthenol e.g., aluminum lactate, sodium lactate, gelatin, sorbitol, or honey.
  • any of the dissolvable matrices disclosed herein may comprise a film forming excipient.
  • film forming excipients generate a film on the outside of a dissolvable matrix.
  • a film forming excipient is present in 1-5%, 1-4%, 1-3%, 1-2%, 2-8%, 2-5%, 2-4%, or 2-5%, 3-5%, or 4-5% (w/w) with respect to the final dissolvable matrix.
  • a film forming excipient is present in about 1%, 2%, 3%, 4%, or 5% (w/w), e.g., about 2%, 2.2%, 2.4%, 2.6%, 2.8%, 3%, 3.2%, 3.4%, 3.6%, 3.8%, 4%, 4.2%, 4.4%, 4.6%, 4.8%, or 5% (w/w) with respect to the final dissolvable matrix.
  • a formulation of dissolvable Matrix la comprises about 3.81% film forming excipient (w/w), a formulation of dissolvable Matrix la comprises about 3.59% film forming excipient (w/w), a formulation of dissolvable Matrix la comprises about 4.16% film forming excipient (w/w), a formulation of dissolvable Matrix 2 comprises about 3.64% film forming excipient (w/w), a formulation of dissolvable Matrix 2a comprises about 2.39% film forming excipient (w/w), and a formulation of dissolvable Matrix 3 comprises about 1.40% film forming excipient (w/w), each relative to the final dissolvable matrix.
  • film-forming excipients include but are not limited to starch, polymerized rosin, pullulan, sodium alginate, Pectin, gelatin, and maltodextrins, Polyvinyl alcohol, hydroxy propyl methyl cellulose, sodium carboxy methyl cellulose, polyvinyl pyrrolidone, proteins (e.g., collagen) and hydroxy propyl cellulose.
  • pullulan is used as an excipient.
  • pullulan acts as a film former to a dissolvable matrix.
  • pullulan is present in 1-5%, 1-4%, 1- 3%, 1-2%, 2-8%, 2-5%, 2-4%, or 2-5%, 3-5%, or 4-5% (w/w) with respect to the final dissolvable matrix.
  • Pullulan is present in about 1%, 2%, 3%, 4%, or 5% (w/w), e.g., about 2%, 2.2%, 2.4%, 2.6%, 2.8%, 3%, 3.2%, 3.4%, 3.6%, 3.8%, 4%, 4.2%, 4.4%, 4.6%, 4.8%, or 5% (w/w) with respect to the final dissolvable matrix.
  • a formulation of dissolvable Matrix la comprises about 3.32% pullulan (w/w)
  • a formulation of dissolvable Matrix la comprises about 3.12% pullulan (w/w)
  • a formulation of dissolvable Matrix 1 comprises about 3.62% pullulan (w/w)
  • a formulation of dissolvable Matrix 2 comprises about 3.16% pullulan (w/w)
  • a formulation of dissolvable Matrix 2a comprises about 2.08% pullulan (w/w)
  • a formulation of dissolvable Matrix 3 comprises about 1.40% pullulan (w/w), each relative to the final dissolvable matrix.
  • the Matrix la-type phospholipidcontaining matrices comprises less than 3.4% pullulan; in contrast, Matrix la-type lacking phospholipids comprise more than 3.8% pullulan.
  • the Matrix la-type phospholipid- containing matrices comprises less than 3.2% pullulan; in contrast, Matrix la-type lacking phospholipids comprise more than 3.5% pullulan.
  • the Matrix 1-type phospholipidcontaining matrices comprises less than 3.7% pullulan; in contrast, the Matrix 1-type lacking phospholipids comprise more than 4% pullulan.
  • the Matrix 2-type phospholipidcontaining matrices comprises less than 3.2% pullulan; in contrast, the Matrix 2-type lacking phospholipids comprise more than 3.5% pullulan.
  • the Matrix 2a-type phospholipidcontaining matrices comprises less than 2.1% pullulan; in contrast, the Matrix 2a-type lacking phospholipids comprise more than 2.3% pullulan.
  • the dissolvable matrices of the present disclosure (which comprise phospholipids, such as lecithin-derived phospholipids) include a reduced amount of pullulan when compared to dissolvable matrices that lack phospholipids.
  • the phospholipid-containing matrices of the present disclosure provide superior flexibility and rate of dissolution when compared to dissolvable matrices that lack phospholipids and have increased amounts of pullulan.
  • Additional classes of excipients useful in the phospholipid-containing matrices of the present disclosure include bulking agents and/or flowing agents.
  • a dissolvable matrix can include other ingredients and/or excipients, including one or more of polymers, defoamers, flow aides, flavor enhancers, rheological modifiers, humectants, waxes, and the like and other components that are utilized to print a layer from an ink, such as dyes, pigments, etc.
  • Exemplary polymers in some instances are water soluble, water swellable, or water insoluble.
  • Defoamers may include, but are not limited thereto, alcohol or polysiloxane type defoamers both in water and alcohol.
  • Flow aids may contain food grade glycols and polyglycols, xylitol, glycerol.
  • Waxes may include, but are not limited to, paraffin or carnauba waxes.
  • Humectants may include, but are not limited to, all molecular weight polyethylene glycols and propylene glycols, xylitol, glycerol sugars and starches.
  • Rheology modifiers may include, but are not limited to, sodium salts of an acrylic polymer, various starches and gums. Colorants may also be used to tint printed compositions to specific colors.
  • Desirable properties of the solid phospholipid-containing matrices of the present disclosure include high mechanical stability and structural integrity (including being shelf- stable), rapidly dissolution in liquid, predictable pore sizes and pore numbers, and low hygroscopicity. Many of these desirable properties are achieved by the choice of and amounts of excipients in a formulation, as disclosed above. In some cases, the methods used to manufacture the dissolvable matrix helps provide the desirable properties.
  • Dissolvable matrices described herein may be sufficiently robust in terms of shelf stability and/or mechanical stability. In some instances, matrices have sufficient stiffness to handle and/or orally ingest and/or place in a food product, such as a beverage, without sagging to a degree that makes handling difficult. Matrices are formulated to not be brittle, such that they resist crumbling when handled under normal conditions.
  • Dissolvable matrices described herein have specific dissolution profiles in a solvent.
  • Solvents can be substantially or mostly pure (e.g., water), but more complex solvents are also contemplated. Solvents include but are not limited to juice, water, tea, milk, coffee, carbonated beverage, fermented beverages (beer, wine, kombucha), soda, or other solvent.
  • a matrix may dissolve (or disintegrate) in a solvent with no or minimal mechanical stirring.
  • a matrix may dissolve in a solvent by active mechanical stirring, such as that achievable by a hand stirring with a spoon, or even a blender or other electrical mixing device.
  • Dissolutions rates of the matrix may be affected by solvent volumes, solvent temperatures, solvent pH, time, or other property of the solvent or the matrix.
  • the surface area of the matrix may affect dissolution rates. In some instances, a larger surface area results in faster dissolution. In some instances, surface is controlled by the shape of the matrix, or pores therein.
  • Dissolvable matrices are configured to dissolve (or disintegrate) in a certain temperature of water (or other aqueous solution) after a certain period of time.
  • immersion comprises contacting dissolvable matrices with excess water (or other aqueous solution).
  • excess water comprises an amount of water (or other aqueous solution) at least 2, 3, 5, 10, 20, 50, or at least 100 times the mass of the dissolvable matrix.
  • a dissolvable matrix e.g., 1.5 inch x 1.5 inch x 200 micron thick matrix
  • dissolution conditions are measured using mechanical stirring.
  • dissolution conditions are measured without the use of mechanical stirring.
  • dissolvable matrices disintegrate without the use of mechanical stirring.
  • dissolution is controlled by formulation (e.g., the choice and amount of excipients or additional components, and whether the active ingredient(s) place the matrix in a category 1, la, 2, or 2a class), the size/ surface area of the matrix, the size/number of pores, and so forth.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than about 15 °C in less than 1, 2, 5, 10, 15, 20, 30, 45, 60, 90, or 120 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than about 15 °C in between 10 and 30 seconds, e.g., about 15 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than 30 °C in less than 1, 2, 5, 10, 15, 20, 30, 45, 60, 90, or 120 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than 30 °C in less than 10 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than 20 °C in less than 1, 2, 5, 10, 15, 20, 30, 45, 60, 90, or 120 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than 20 °C in less than 60 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than 10 °C in less than 1, 2, 5, 10, 15, 20, 30, 45, 60, 90, or 120 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than 10 °C in less than 60 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than 5 °C in less than 1, 2, 5, 10, 15, 20, 30, 45, 60, 90, or 120 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of no more than 5 °C in less than 60 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of about 0 °C in less than 1, 2, 5, 10, 15, 20, 30, 45, 60, 90, or 120 seconds.
  • the dissolvable matrix may be configured to dissolve in water (or other aqueous solution) having a temperature of about 0 °C in less than 60 seconds.
  • the dissolvable matrix may be configured to dissolve in no more than 8 oz of water (or other aqueous solution) having a temperature of no more than 20 °C in less than 60 seconds.
  • the dissolvable matrix may be configured to dissolve in no more than 8 oz of water having a temperature of no more than 20 °C in less than 30 seconds.
  • the dissolvable matrix may be configured to dissolve in an aqueous solution having a pH of about 2 to 10.
  • dissolvable matrix may be configured to dissolve in water (or other aqueous solution) [at a specified temperature and for a specified length of time]” means that at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%, or 100% by mass of the original dissolvable matrix has dissolved into the aqueous solution.
  • Dissolvable matrices described herein may have different surface areas which may influence dissolution.
  • the dissolvable matrix surface area is not measured to include pores (i.e., treated as a flat external surface based on overall shape).
  • a dissolvable matrix has a surface area of at least 100, 200, 500, 800, 1000, 2000, 5000, 8000, 10,000, 12,000, 15,000, or at least 20,000 mm 2 .
  • a dissolvable matrix may have the size and dimensions of an 8 1/2” by 11” sheet.
  • a dissolvable matrix may have a surface area of about 100, 200, 500, 800, 1000, 2000, 5000, 8000, 10,000, 12,000, 15,000, or about 20,000 mm 2 .
  • a dissolvable matrix has a surface area of 100-10,000, 100-20,000, 200-10,000, 500-10,000, 1000-10,000, 5000-10,000, 9000-15,000, or 7000-20,000 mm 2 .
  • a formulation may additionally or alternatively comprise one or more of polyvinyl alcohol, polysaccharides (e.g., Pullulan), sodium alginate, carrageenan, xanthan gum, or guar gum to regulate dissolution.
  • polysaccharides e.g., Pullulan
  • sodium alginate e.g., carrageenan
  • xanthan gum e.g., xanthan gum
  • guar gum e.g., guar gum
  • a dissolvable matrix may be configured such that the dissolution of the active or other ingredients (e.g., sweeteners and flavors) within the dissolvable matrix may be released over a period of time.
  • the period of dissolution or dispersion may be adjusted based on the amount of starch, as an example, such as a slower period of dissolution or dispersion when more starch is used and quicker dissolution or dispersion when less starch is used (or vice versa).
  • a binder may be added to the dissolvable matrix to maintain the structural integrity of the substances therein. Binders may include one or more of polysaccharides (e.g., Pullulan,) sodium alginate, etc.
  • the entire dissolvable matrix and/or individual layers of the dissolvable matrix may include be subjected to micro-scoring and/or pinholes. By doing such, the surface area of the dissolvable matrix and/or layers is increased, thereby allowing for faster dissolution/dispersion.
  • the support substrate may be configured such that the dissolution or dispersion of the support substrate may be performed over a period of time.
  • additional components such as starches may be mixed with polyvinyl alcohol and into one of the materials for generating the printable support substrate such as carrageenan, xanthan gum, guar gum, etc.
  • the period of dissolution or dispersion may be adjusted by adjusting the formulation of the composition. For instance, based on the ingredients contained in the composition, such as the amount starch, the dissolution or dispersion rate may be adjusted. In one such example, a slower period of dissolution or dispersion may occur when more starch is used and quicker dissolution or dispersion when less starch is used.
  • a binder may be added to the dissolvable matrix to maintain the structural integrity of the substances therein.
  • the support substrate may include supplements or other active ingredients.
  • Dissolvable matrices described herein comprise a plurality of pores, which form during the manufacturing process, e.g., as a result a blowing agents, which promote pore formation and help create structure in the matrix.
  • the blowing agents Prior to curing, the blowing agents incorporate or trap air (or other gas, e.g., CO2), e.g., create a froth, from a liquid composition comprising the active ingredients and excipients.
  • air or other gas, e.g., CO2
  • a froth e.g., a froth
  • a void in the matrix e.g., a volume that is not occupied by solid matter.
  • these pores contribute to improved handling and dissolution properties of the matrix.
  • the voids increase the surface area contactable by a liquid solvent when dissolving a matrix.
  • the matrix comprises at least 0.5%, 1%, 1.5%, 2%, 3%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, or at least 70% void space (v/v).
  • the matrix comprises about 0.5%, 1%, 1.5%, 2%, 3%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, or about 70% void space (v/v).
  • the matrix comprises no more than 0.5%, 1%, 1.5%, 2%, 3%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, or no more than 70% void volume/space (v/v). ).
  • the matrix comprises a void volume of 1-70%, 1-60%, 1-50%, 1-40%, 1-30%, 1-25%, 2-70%, 2-50%, 2-30%, 3-75%, 3-50%, 3-30%, 3-25%, 4-40%, 4-30%, 4-25%, 4-20%, 4-10%, 5-50%, 5-75%, 5-25%, 10-70%, 10-50%, 25-75%, or 50-75%.
  • the pore size is expressed as the longest linear dimension of a pore (e.g., longest cross-sectional length).
  • the average pore size e.g., based on light microscopy images, for a bottom surface of a phospholipid-containing matrix of the present wis about 0.1, 0.2, 0.3, 0.5, 1, 2, 3, 5, 10, 20, 50, or about 100 microns. In some instances, the average pore size is no more than 0.1, 0.2, 0.3, 0.5, 1, 2, 3, 5, 10, 20, 50, or no more than 100 microns.
  • the average pore size is 0.1-50, 0.2-20, 0.5-50, 1- 20, 1-50, 1-100, 5-100, 10-100, 10-200, 50-200, 100-200, 100-300, 150-300, 10-50, or 5-50 microns.
  • the median pore size is no more than 0.1, 0.2, 0.3, 0.5, 1, 2, 3, 5, 10, 20, 50, or no more than 100 microns.
  • the median pore size is 0.1-50, 0.2-20, 0.5-50, 1-20, 1-50, 1-100, 5-100, 10-100, 10-200, 50-200, 100-200, 100-300, 150-300, 10-50, or 5-50 microns.
  • the mean pore size is 100-1000, 100-2000, 100- 3000, 100-4000, 100-5000, 100-6000, 500-1000, 500-2000, 500-3000, 500-4000, 1000-2000, 1000-3000, 1000-5000, 2000-3000, 2000-4000, 2000-5000, 3000-4000, 3000-5000, 3000- 6000, 4000-6000 or 5000-6000 square microns.
  • the median pore size is 100-1000, 100-2000, 100-3000, 100-4000, 100-5000, 100-6000, 500-1000, 500-2000, 500- 3000, 500-4000, 1000-2000, 1000-3000, 1000-5000, 2000-3000, 2000-4000, 2000-5000, 3000-4000, 3000-5000, 3000-6000, 4000-6000 or 5000-6000 square microns.
  • pores are approximated as spherical.
  • pore size is measured as the longest cross-sectional diameter of the pore.
  • the pore size is expressed as a cross-sectional area of a pore.
  • the average cross-sectional area of pores is 1000-25,000, 1000-20,000, 1000-10,000, 1000-5000, 1500-12,000, 1500-7000, 1500-5000, 2500-25,000, 5000-25,000, 10,000-25,000, 15,000-25,000, or 7000-12000 square microns. In some instances, the average cross-sectional area of pores has a standard deviation of 1 GOO- 25, 000, 1000-20,000, 1000-10,000, 1000-5000, 1500-12,000, 1500-7000, 1500-5000, 2500- 25,000, 5000-25,000, 10,000-25,000, 15,000-25,000, or 7000-12000 square microns.
  • the bottom surface of a dissolvable matrix of the present disclosure is the surface that contacted the stencil’s surface during formation of the matrix.
  • Dissolvable matrices may have a pore density.
  • the pore density is expressed in two dimensions as pores per unit area.
  • the pore density is expressed in three dimensions as pores per unit volume.
  • the pore density is between about 1-500, 1-250, 1-200, 1-150, 1-100, 10-500, 10-300, 10-200, 10-100, 25-150, 25-250, 50-100, 50-250, or between about 50-500 pores per square mm.
  • the pore density is at least 1, 2, 5, 10, 15, 20, 25, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 300, 350, or at least 400 pores per square mm.
  • a dissolvable matrix comprises at least 1, 5, 10, 50, 100, 500, 1000, 5000, 10,000, or at least 50,000 pores per cubic mm. In some instances, a dissolvable matrix comprises about 1, 5, 10, 50, 100, 500, 1000, 5000, 10,000, or about 50,000 pores per cubic mm. In some instances, a dissolvable matrix comprises no more than 1, 5, 10, 50, 100, 500, 1000, 5000, 10,000, or no more than 50,000 pores per cubic mm.
  • a dissolvable matrix comprises 1-100,000, 1-50,000, 1-10,000, 1-5000, 1-1000, 1-100, 10-100, 10-1000, 50-500, 50-1000, 100-10,000, 100-5,000, 1000-100,000, 1000-50,000, 100-10,000, 100-1000, or 500-5000 pores per cubic mm.
  • the dissolvable matrices of the present disclosure may have — on a bottom surface — pores that substantially lack jagged edges and/or interpore regions that substantially lack trabeculated structures. Compare the smooth pores and interpore regions shown in FIG. 3B of an illustrative phospholipid-containing matrix of the present disclosure with the jagged edges and trabeculated interpore regions for a matrix lacking phospholipids (as shown in FIG. 2B). Thus, the phospholipid-containing matrices of the present disclosure show signs of proper emulsification and homogeneity.
  • the porosity of a dissolvable matrix described herein may be measured analytically.
  • a dissolvable matrix is analyzed using microscopy.
  • microscopy comprises light, electron, scanning probe, or x-ray spectroscopy.
  • a matrix is imaged by light microscopy and pores are measured and quantified using ImageJ or similar software.
  • a matrix is mounted directly to a scanning electron microscopy (SEM) stud.
  • SEM scanning electron microscopy
  • microscopy comprises SEM.
  • SEM is performed at 3.0kV.
  • a dissolvable matrix is frozen (e.g., with liquid nitrogen or other agent) and fractured to produce a cross-section for mounting and analysis.
  • images are obtained from different planes of a dissolvable matrix.
  • images are obtained from one or more of x-y and z planes, where the x-y plane is a plane that corresponds with or is parallel to a principal surface of a matrix or disk, while the z plane is perpendicular to the x-y plane.
  • a dissolvable matrix is cut or fractured at room temperature to produce a cross-section for analysis. Images may then be obtained from the cross-section, and analyzed using a computer algorithm. The analysis in some instances measures void volume (% of total focal area, assuming spherical pores), average pore size, pore distribution, surface area per volume (taking into account the pores, and/or other measurement).
  • the x-y plane corresponding to the top (distal to a curing surface) of the dissolvable matrix is imaged.
  • one or more computer transformation steps are utilized to generate data for pores.
  • steps comprise one or more of opening an SEM image file, setting or defining the scale of the image, duplicating the image, converting the image to 8-bit grayscale type, setting a color threshold to represent pores in original image, processing or touching up the image based on features in the original image, sorting particles by minimum pore size, and logging data.
  • Calculation of values in some instances comprises removal of one or more SEM images which do not meet minimum quality standards.
  • at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 images are analyzed.
  • 1-10, 1-6, 2-6, 2-4, or 6-12 images are analyzed, e.g.,. using ImageJ or a similar program.
  • Dissolvable matrices described herein may have sufficiently low hygroscopicity to allow facile handling under various humidity conditions.
  • standard temperature and pressure (STP) used for measuring hygroscopicity were 0 degrees C at 1 atm.
  • temperature and pressure used for measuring hygroscopicity were 20 degrees C at 1 atm.
  • absorbance of moisture is measured as an initial rate. In some instances, the initial rate is measured during about the first minute, two minutes, five minutes, 10 minutes, 15 minutes, 30 minutes, hour, two hours, three hours, four hours, or 12 hours.
  • the initial rate is measured during 0-30 minutes, 0-60 minutes, 0-2 hours, 0-3 hours, 0-4 hours, 0-5 hours, or 0-6 hours. In some instances, the initial rate is no more than 0.1, 0.05, 0.04, 0.03, 0.02, 0.015, 0.010, or no more than 0.005 % per minute. In some instances, the initial rate (measured for the first 4 hours) is no more than 0.1, 0.05, 0.04, 0.03, 0.02, 0.015, 0.010, or no more than 0.005 % per minute.
  • the initial rate is 0.010-0.1, 0.010-0.2, 0.010-0.3, 0.010-0.04, 0.010-0.05, 0.010-0.07, 0.010-0.080, 0.02-0.05, 0.01-0.03, 0.015-0.03, or 0.03-0.05 % per minute. In some instances, the initial rate is 0.010- 0.1, 0.010-0.2, 0.010-0.3, 0.010-0.04, 0.010-0.05, 0.010-0.07, 0.010-0.080, 0.02-0.05, 0.01- 0.03, 0.015-0.03, or 0.03-0.05 % per minute for the first 4 hours.
  • a matrix may absorb less than 1% (w/w) moisture per min at 50% humidity, e.g., less than 0.1%, 0.01%, or 0.01% (w/w) moisture per min at 50% humidity at standard temperature and pressure.
  • a matrix may absorb less than 1% (w/w) moisture per min at 75% humidity, e.g., less than 0.1%, 0.01%, or 0.01% (w/w) moisture per min at 75% humidity at standard temperature and pressure.
  • a matrix may absorb less than 1% (w/w) moisture per min at 90% humidity, e.g., less than 0.1%, 0.01%, or 0.01% (w/w) moisture per min at 90% humidity at standard temperature and pressure.
  • a matrix may absorb less than 1% (w/w) moisture per min at 50% humidity, e.g., less than 0.1%, 0.01%, or 0.01% (w/w) moisture per min at 50% humidity at standard temperature and pressure.
  • a matrix may absorb less than 1% (w/w) moisture per min at 75% humidity, e.g., less than 0.1%, 0.01%, or 0.01% (w/w) moisture per min at 75% humidity at standard temperature and pressure.
  • a matrix may absorb less than 1% (w/w) moisture per min at 90% humidity, e.g., less than 0.1%, 0.01%, or 0.01% (w/w) moisture per min at 90% humidity at standard temperature and pressure.
  • a dissolvable matrix may be generated such that the matrix resists reaching a threshold water content (e.g., water activity or percent moisture). In some instances this facilitates handling of the matrix and/or removal of the matrix from a substrate or support (e.g., foil, wrapper, or other substrate).
  • a dissolvable matrix comprises a water activity of no more than 0.5, 0.45, 0.4, 0.35, 0.3, 0.25 0.2, or no more than 0.1.
  • a dissolvable matrix comprises a water activity of no more than 0.5, 0.45, 0.4, 0.35, 0.3, 0.25 0.2, or no more than 0.1 under conditions comprising 20 degrees C, latm, and 45% relative humidity.
  • a dissolvable matrix comprises a water activity of no more than 0.5, 0.45, 0.4, 0.35, 0.3, 0.25 0.2, or no more than 0.1 under conditions comprising 20 degrees C, latm, and 45% relative humidity after no more than 2 hours. In some instances, a dissolvable matrix comprises a water activity of no more than 0.5, 0.45, 0.4, 0.35, 0.3, 0.25 0.2, or no more than 0.1 under conditions comprising 20 degrees C, latm, and 45% relative humidity after no more than 4 hours.
  • a dissolvable matrix comprises a water activity of no more than 0.5, 0.45, 0.4, 0.35, 0.3, 0.25 0.2, or no more than 0.1 under conditions comprising 20 degrees C, latm, and 45% relative humidity after no more than 1 hour.
  • a matrix herein can include one or more active ingredients, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 active ingredients.
  • Such active ingredients include but are not limited to pharmaceuticals, nutraceuticals, plant, animal, or fungal extracts, or other active ingredients that promote health.
  • Active ingredients can comprise prebiotics, fruit or vegetable extracts, minerals, amino acids, vitamins or another active ingredient.
  • Active ingredients such as prebiotics for example, can promote gut flora or microbiota health.
  • Prebiotics include, but are not limited to, bacteriophages, polyphenols, and other.
  • Other examples of active ingredients include sleep enhancers configured to promote sleep (quantity, quality, etc.), stimulants such as caffeine, steroids and the like.
  • Active ingredients can be immunity enhancers, configured to promote enhanced immunity from diseases or conditions. In some instances, the active ingredient comprises a pharmaceutical or nutraceutical.
  • the percentage of active ingredients in some instances is measured as a percent dry weight after curing.
  • the percentage of active ingredients in some instances is measured as a percent weight prior to mixing.
  • Dissolvable matrices comprise a surprisingly high percentage of active ingredients(s).
  • a phospholipid-containing matrix of the present disclosure may comprise between about 35% and 65% (w/w) of active ingredient(s) relative to the entire dissolvable matrix.
  • the total active ingredients may comprise about 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, or 65% (w/w) with respect to the final dissolvable matrix.
  • a dissolvable matrix may comprise one to ten active ingredients.
  • the amount of each active ingredient in a matrix can be the same or differ.
  • One active ingredient may be present in a greater amount the other active ingredients, e.g., 2-fold, 5-fold, 10-fold, 50-fold 100-fold, and 200-fold more; one active ingredient may be present in a lesser amount that the other active ingredients.
  • One active ingredients may comprise less than 1% of the total weight of a dissolvable matrix, e.g., about 0.1%, 0.2%, 0.5%, or 0.8%; another active ingredient may comprise more than 30% of the total weight of a dissolvable matrix, e.g., about 30%, 31%, 32%, 33%, 34%, and 35%.
  • an active ingredient in a dissolvable matrix can be at least 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% (w/w) relative to relative to the entire dissolvable matrix.
  • the totality of the active ingredients in a dissolvable matrix can be between 35-45%, 35-55%, 35-65%, 45- 55%, 45-65% or 55-65% (w/w) relative to relative to the entire dissolvable matrix.
  • Active ingredients can be present in at least 10, 20, 30, 40 50, 100, 200, 500, 800, 1000, 2000, or at least 5000 mg per 10 cm 2 of a matrix. In some instances, active ingredient(s) are present in 500-800, 100-800, 50-200, 100-500, 200-800, 500-1000, or 500-1500 mg per 10 cm 2 of a matrix.
  • the prebiotic can comprise a bacteriophage component.
  • the bacteriophage component can comprise one or more lytic bacteriophages, such as, e.g., Siphoviridae or Myoviridae family, or more specifically, CHOI -My oviridae, LL5- Siphoviridae , l ⁇ D-Myoviridae, or LL ⁇ 2-Myoviridae.
  • a bacteriophage component is one that accelerates growth of one or more ofB. bifidum; B breve; B. animalis subsp. lactis; B. longum; L. acidophilus; L.
  • a bacteriophage component can be one that supports increases in the concentration of butyrate-producing Eubacteria, decreases the concentration of Clostridium perfringens, or decreases interleukin 4 (IL-4) cytokine.
  • a bacteriophage can be one targets one or more pathogenic bacteria. In some instances, the bacteriophage targets Escherichia coli and related species.
  • a matrix described herein can comprise between about 1-5%, 0.5-5%, 0.5- 10%, 0.1-5%, 1-10%, 1.5-8%, 2-5%, or 2-6% (w/w) of a bacteriophage component or alternatively about 0.5%, 0.8%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4% or about 5% of a prebiotic component (w/w) relative to the entire dissolvable matrix.
  • a dissolvable matrix comprises about 2.9% the bacteriophage component (w/w) relative to the entire dissolvable matrix.
  • PreforPro is an illustrative prebiotic comprising a bacteriophage component.
  • a dissolvable matrix can comprise one or more extracts.
  • extracts contemplated herein include a fruit extract, a vegetable extract, or a tea leaf extract. Any of the extracts herein can comprise one or more polyphenols.
  • Examples of fruit extracts include blueberry, cherry, pomegranate, strawberry, banana, coconut, elderberry, currant, grape skin, pineapple, mango, papaya, kiwi, orange, paw, mangosteen, acai, lemon, lime, grapefruit, cumquat, bergamot, tomato, and apple extract.
  • a blueberry extract herein can be derived from, e.g., Vaccinium spp. such as Vaccinium alaskaense How; Vaccinium ovaliforium Sm; Vaccinium membranaceum L. Vaccinium uliginosum L. or Vaccinium cespitosum Mich X.
  • a matrix described herein can comprise about 1-15%, 1-20%, 5-25%, 10-20%, 10-25%, 15-25%, 5-10%, or 8-18% (w/w) of a blueberry extract or about 5%, 7%, 9%, 10%, 12%, 15%, 16%, 17%, 20%, 22%, 25%, or about 30% of a blueberry extract (w/w) each relative to the entire dissolvable matrix.
  • a pomegranate extract e.g., a pomegranate polyphenol powder
  • Punica spp. such as Punica granatum. Examples of pomegranate be, e.g., ellagitannins or punicalagins.
  • a matrix described herein can comprise about 0.5-15%, 1-10%, 5-10%, 5-15%, 2-17%, 4-16%, 2-8%, or 2-15% (w/w) of a pomegranate extract or about 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 15%, or about 20% of a pomegranate extract (w/w) each relative to the entire dissolvable matrix.
  • a dissolvable matrix comprises about 15.69% blueberry powder and about 7.85% pomegranate extract (w/w) each relative to the entire dissolvable matrix.
  • An illustrative cherry extract is acerola (cherry) powder.
  • a dissolvable matrix comprises about 1.63% acerola powder (w/w) relative to the entire dissolvable matrix.
  • a vegetable extract can be any one or more of the following: turmeric, beet root, broccoli, daikon, garlic, chicory, asparagus, cucumber, celery, fennel, potato, legume, resistant starch, ginger, onion, artichoke, olive, spinach, cabbage, brussels sprouts, carrot, leek, pepper, or mushroom extract. Vegetable extracts can be used as coloring agents as well as active ingredients.
  • Active ingredients may comprise one or more polyphenols.
  • the polyphenol comprises flavonoids, phenolic acids, polyphenolic amides, or other type of polyphenol.
  • flavonoids comprise quercetin, kaempferol, catechins, and anthocyanins.
  • phenolic acids comprise stilbenes or lignans.
  • polyphenolic amides comprise capsaicinoids or avenanthramides.
  • polyphenols comprise resveratrol, ellagic acid, curcumin, or lignans.
  • polyphenols comprise Anthocyanidins (e.g., cyanidin), Anthoxanthins, Flavones (e.g., apigenin), Flavanols (e.g., catechin), Flavanones (e.g., naringenin) Flavonols (e.g., quercetin and kaempferol), Flavans (e.g., leucoanthocyanidin), Isoflavones (e.g., daidzein), Isoflavanes (e.g., laxiflorane), Isoflavandiols, Isoflavenes (e.g., glabrene), Coumestans (e.g., wedelolactone) Pterocarpans (e.g., glyceollins), Stilbenoids (e.g., resveratrol), or Proanthocyanidins, Oligostilbenoids
  • Active ingredients may comprise compounds or mixtures obtained from botanical sources.
  • an active ingredient comprises lecithinized botanical extracts.
  • a lecithinized botanical extract comprises phytosomes.
  • a lecithinized botanical extract comprises quercetin, grape seed, green tea, diindolylmethane (DIM), or curcuminoid.
  • a tea leaf extract can be a green tea extract or a black tea extract.
  • a green tea extract can be obtained from Camellia spp such as Camellia sinensis.
  • a green tea extract can include caffeine or be caffeine free (e.g., ⁇ 1 % w/w caffeine).
  • a green tea extract can include at least 19% catechins (w/w: weight of catechin relative to weight of the green tea extract).
  • a green tea extract can comprise at least 5%, 10%, 15%, 20%, or at least 25% catechins (w/w: weight of catechin relative to weight of the green tea extract).
  • Catechins contemplated can be selected from the group consisting of: (-)-epigallocatechin; (+)-catechin; (-)-epicatechin; (-)-epigallocatechin 3-O-gallate; (+)-gallocatechin 3-O-gallate; (-)- epigallocatechin 3-O-(3’-O-methyl)-gallate; and (-)-epicatechin 3-O-gallate.
  • the green tea extract comprises at least 5%, 10%, 12%, 13%, 14%, 15%, or at least 20% (-)-epigallocatechin 3-O-gallate (EGCG) (w/w: weight of EGCG relative to weight of the green tea extract).
  • any of the green tea extracts herein can include one or more of hydrobenzoic acids; hydroxycinnamic acids; or flavones.
  • a green tea extract can further comprises soy phospholipids.
  • a matrix described herein comprises between about 2-25%, 2-20%, 5-15%, 5- 10%, 6-9%, 10-20%, 26%, or 7-15% (w/w) of a green tea extract or about 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 16%, 17%, or 20% of a green tea extract (w/w) relative to the entire dissolvable matrix.
  • a dissolvable matrix comprises about 15.69% green tea extract (w/w) relative to the entire dissolvable matrix
  • An active ingredient can be a sleep enhancer that improves sleep quality and/or quantity.
  • the sleep enhancer can be a chamomile extract, L-theanine, melatonin, or a mixture thereof.
  • the chamomile extract can be obtained from matricaria recutita or Matricaria chamomilla.
  • Chamomile extracts comprise at least 0.5%, 0.7%, 0.9%, 1%, 1.1%, 1.2%, 1.5%, or at least 2% apigenin (w/w: weight apigenin relative to weight of the chamomile extracts).
  • a matrix described herein can comprise 1- 15%, 1-20%, 5-25%, 10-20%, 10-25%, 15-25%, 5-10%, or 8-18% (w/w) chamomile extract relative to the entire dissolvable matrix.
  • a matrix described herein can comprise about 5%, 7%, 9%, 10%, 12%, 15%, 16%, 17%, 20%, 22%, 25%, or about 30% (w/w) of a chamomile extract relative to the entire dissolvable matrix.
  • a matrix described herein can comprise 10-15%, 10-20%, 5-35%, 10-40%, 10-45%, 15-50%, 25-40%, or 25-45% (w/w) of L-theanine relative to matrix weight.
  • a matrix described herein can comprise about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or about 55% (w/w) of L-theanine relative to matrix weight.
  • a matrix described herein can comprise 0.1-0.15%, 0.1-0.2%, 0.01-0.3%, 0.1-0.25%, 0.1-0.3%, 0.15- 0.5%, 0.25-0.3%, or 0.08-0.2% (w/w) melatonin relative to matrix weight.
  • a matrix described herein can comprise about 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.40%, or about 0.5% (w/w) melatonin relative to matrix weight.
  • a dissolvable matrix comprises about 15.81% chamomile extracts (w/w), about 33.28% L-theanine (w/w), and about 0.17% melatonin (w/w), each relative to the entire dissolvable matrix.
  • An active ingredient can improve immunity.
  • An active ingredient that improves immunity can be a lecithinized.
  • the lecithinized product can be a quercetin lecithin complex.
  • a matrix described herein can comprise 10-15%, 10- 20%, 5-35%, 10-40%, 10-45%, 15-50%, 25-40%, or 25-45% (w/w) lecithin complex relative to the entire dissolvable matrix.
  • a matrix described herein can comprise about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or about 55% (w/w) lecithin complex relative to the entire dissolvable matrix.
  • An active ingredient that improves immunity can additionally or alternatively be a vitamin or mineral, e.g., vitamin D3, ascorbic acid (i.e., vitamin C), a zinc salt, or zinc chelate (e.g., zinc picolinate).
  • a matrix described herein can comprise 1-5%, 1-10%, 1-3%, 2-8%, 3-10%, 2.5-4%, 1-4%, or 0.5-4% (w/w) vitamin D3 relative to matrix weight.
  • a matrix described herein can comprise about 0.5%, 1%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, or about 5.5% (w/w) vitamin D3 relative to the entire dissolvable matrix.
  • a matrix described herein can comprise 10-15%, 10-20%, 5-35%, 10-40%, 10-45%, 15-50%, 25-40%, or 25-45% (w/w) of ascorbic acid or about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or about 55% (w/w) of ascorbic acid, each relative to the entire dissolvable matrix.
  • a matrix described herein can comprise about 5-15%, 5-20%, 5-35%, 10-40%, 10-45%, 15-50%, 25-40%, or 25-45% (w/w) of zinc salt or about 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or about 55% (w/w) zinc salt relative to matrix weight.
  • the zinc salt is a zinc chelate.
  • the zinc salt is zinc picolinate.
  • a dissolvable matrix comprises about 29.83% quercetin lecithin complex (w/w), about 3.58% vitamin D3 (w/w), about 13.72% ascorbic acid (w/w), and about 8.95% zinc picolinate (w/w), each relative to the entire dissolvable matrix.
  • Active ingredients may include supplements and the supplements may include those suitable for nutrition, flavor enhancement, and/or medicinal purposes that can be ingested.
  • Nutritional supplements can include a vitamin, a mineral, a protein, a probiotic, a fiber, an amino acid, and other dietary supplements.
  • vitamins in some instances include any suitable vitamin that can be ingested, such as vitamin A, B, C, D, E, B12, and the like found in a typical over the counter multivitamin.
  • Minerals in some instances include iron, magnesium, potassium, and the like found in a typical over the counter multivitamin/multimineral.
  • a protein in some instances includes whey protein or a plant-based protein.
  • the active and inactive ingredients include pharmaceuticals, such as acetylsalicylic acid, acetaminophen, ibuprofen, etc., as well as beverage and food items.
  • the active ingredient is or comprises one or more of Lutein (from Lutemax 2020 (Tagetes erecta)), Zeaxanthin (from Lutemax 2020 (Tagetes erecta)), Vitamin A (120 mcg RAE as Beta Carotene), Vitamin C (as Ascorbic Acid), Vitamin D (as Healthy Vitamin D3) (800 IU), Vitamin E (as d-Alpha Tocopherol from Mixed Tocopherols), Vitamin K2 (as MK-7), Zinc (as Zinc Bisglyccommune), Riboflavin (as Riboflavin 5' - Phosphate Sodium), Vitamin B6 (as Pyridoxal 5'-Phosphate), Folate (as L-5-Methyltetrahydrofolate), Vitamin B 12 (as Methylcobalamin), Choline (as Choline Citrate), iodine (as Potassium Iodide), Magnesium (Lutemax 2020 (Tage
  • the active ingredient is or comprise one or more of Lutein in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Zeaxanthin in an amount of about 0.2 mg per 1.4 g dry dissolvable matrix, Vitamin A in an amount of about 0.12 mg per 1.4 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.4 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 0.02 mg per 1.4 g dry dissolvable matrix, Vitamin E in an amount of about 7.5 mg per 1.4 g dry dissolvable matrix, Vitamin K2 in an amount of about 0.05 mg per 1.4 g dry dissolvable matrix, Zinc in an amount of about 5 mg per 1.4 g dry dissolvable matrix, Riboflavin in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Vitamin B6 in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Folate in an amount of about 0.3 mg per
  • a dissolvable matrix comprises two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or sixteen of the above mentioned active ingredients.
  • the amounts of the above listed active ingredients may be increased by a factor of 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 100, 1,000 or more.
  • the amounts of the above-listed active ingredients may be reduced by 1/2, 1/3, %, 1/5, 1/6, 1/7, 1/8, 1/9, 1/10, 1/20, 1/30, 1/40, 1/50, 1/100, or 1/1,000 and so forth.
  • the active ingredient(s) are or comprise one or more of Lutein in an amount of about 1 mg per 1.8 g dry dissolvable matrix, zeaxanthin in an amount of about 0.20 mg per 1.8 g dry dissolvable matrix, Vitamin A in an amount of about 1.34 mg per 1.8 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.8 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 0.02 mg per 1.8 g dry dissolvable matrix, Vitamin E in an amount of about 7.5 mg per 1.8 g dry dissolvable matrix, Vitamin K2 in an amount of about 0.05 mg per 1.8 g dry dissolvable matrix, Zinc in an amount of about 5 mg per 1.8 g dry dissolvable matrix, Riboflavin in an amount of about 1 mg per 1.8 g dry dissolvable matrix, Vitamin B6 in an amount of about 1 mg per 1.8 g dry dissolvable matrix, Folate in an amount of about
  • a dissolvable matrix comprises two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or sixteen of the above mentioned active ingredients.
  • the amounts of the above listed active ingredients may be increased by a factor of 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 100, 1,000 or more.
  • the amounts of the above-listed active ingredients may be reduced by 1/2, 1/3, %, 1/5, 1/6, 1/7, 1/8, 1/9, 1/10, 1/20, 1/30, 1/40, 1/50, 1/100, or 1/1,000 and so forth.
  • An active ingredient or mixture of two or more active ingredients described herein may comprise a lipophilicity value or be designated lipophilic. Such a classification in some instances is used to choose optimum conditions for generating a dissolvable matrix. In some instances, the lipophilicity is measured by a logP value, wherein higher values indicate more lipophilic character. In some instances, lipophilicity is compared to a threshold value to determine if the agent or mixture is lipophilic (e.g., if a threshold is 1.5 and the agent is 2, the agent is lipophilic).
  • the lipophilicity threshold is about -1.5, -1.25, -1, -0.5, -0.25, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9 or about 10. In some instances, the lipophilicity threshold is at least -1.5, -1.25, -1, -0.5, -0.25, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9 or at least 10.
  • the lipophilicity threshold is -1.5-10, -1.5-5, -1.5-5, -0.01-10, 0.01-7, 0.01-5, 0.01-2, 0.05-5, 0.1-10, 0.2-10, 0.5-10, 1-10, 1.5-10. 2-10, or 5-15.
  • a dissolvable matrix can have one or more colors added.
  • a natural colorant such as turmeric, beet root, or another colorant, is used. Colorants may be chosen to resist photobleaching or color change during sunlight exposure or storage. In some instances, an artificial colorant added, such a food-grade coloring.
  • a dissolvable matrix may comprise one or more excipients to create a flavor.
  • a dissolvable matrix may comprise a sweetener.
  • Sweeteners include but are not limited to xylitol, sugar, dextrose, acesulfame potassium, aspartame, neotame, saccharin, sucralose, or stevia extract. Natural or artificial sweeteners may be used.
  • a flavoring comprises an extract from a fruit, such as lemon (e.g., Meyer lemon), orange, cherry (e.g., acerola), raspberry, watermelon, apple, pomegranate, or other fruit. Extracts may be blended to produce additional flavors.
  • Citric acid may be used as a flavoring excipient, e.g., to provide acidity.
  • a solid dissolvable matrix can be in the form of a rectangular or square strip, sheets, a cube, a sphere, a disk, oval, star, snowflake, decorative design, recognizable shape (e.g., animal shape, logo, icon, or TV/movie/comic character) and the like.
  • the dissolvable matrix can vary in dimensions. Such variation in size may be dependent on application.
  • an individual matrix may range in length or diameter from about 1 mnv l mm to about 12 inches by 12 inches; these larger lengths or diameters are possible, for example, such as when the dissolvable matrix is formed (i.e., printed) as a sheet for large-scale production or when a large sheet is cut into individual matrices.
  • the matrix is substantially two dimensional (sheet, disk, rectangle, square, donut, strip, or other shape). In some instances, the matrix is substantially three dimensional (cylinder, sphere, cube, prism, pyramid, torus). In some instances, a two dimensional matrix comprises a smallest linear dimension that is about 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, or about 200 times smaller than the largest linear dimension.
  • a two dimensional matrix comprises a smallest linear dimension which is about 2-200, 2-150, 2-125, 2-100, 2-50, 2-25, 5-500, 5-250, 5-150, 10-100, 10-200, 10-300, 25-400, 25-300, 25-250, 25-100, 50-100, 50- 200, 50-300, 50-500 100-250, 100-500, 100-500, or 250-500 times smaller than the largest linear dimension.
  • a dissolvable matrix has a longest cross-sectional length of 0.1- 0.2, 0.2-0.3, 0.3-0.4, 0.5-4, 0.5-3, 0.5-3, 1-3, 1-2, 1.5-3.5 or 1.5-2.5 inches. In some instances, a dissolvable matrix has a longest cross-sectional length of about 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, or about 3 inches. In some instances, a dissolvable matrix has a longest cross-sectional length of no more than 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, or no more than 3 inches.
  • the dissolvable matrix may have the size and shape of an 8 ’ ” by 11” cover sheet.
  • the dissolvable matrix comprises a largest cross-sectional area of about 0.5, 1, 1.25, 1.5, 2.0, 2.25, 2.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 6.5, or about 7 square inches.
  • the dissolvable matrix comprises a largest cross-sectional area of no more than 0.5, 1, 1.25, 1.5, 2.0, 2.25, 2.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 6.5, or no more than 7 square inches.
  • the dissolvable matrix comprises a largest cross-sectional area of at least 0.5, 1, 1.25, 1.5, 2.0, 2.25, 2.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 6.5, or at least 7 square inches. In some instances the dissolvable matrix comprises a largest cross-sectional area of 0.2-10, 0.5-10, 1-10, 2-10, 0.5-7, 1-7, 2-5, 2-7, 2-12, 3-5, 3-10, or 5-10 square inches.
  • a dissolvable matrix may range in thickness from about 1 microns to about 50 mm, or greater than 15 mm. In some instances, a disc’s thickness is measured as an average thickness.
  • a dissolvable matrix may have a thickness of 50-500, 100-1000, 100-500, 200-700, 300-700, 400-500, or 400-1000 microns. In some instances, the thickness is about 1, 10, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, or about 2000 microns.
  • the thickness is no more than 1, 10, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, or no more than 2000 microns. In some instances, the thickness is 250 to 1000 microns. In some instances, the thickness is 150 to 1500 microns. In some instances, the thickness is between 50 to 500 microns. In some instances, the thickness is between 50-500, 25-1000, 25- 500, 25-250, 25-100, 50-250, 75-750, 100-250, 100-500, 100-1000, or between 45-750 microns. In some cases, a dissolvable matrix (e.g., that weighs about 1.4 grams) is from about 0.75 mm to about 1.0 mm for the z-axis.
  • a dissolvable matrix e.g., that weighs about 1.4 grams
  • the solid dissolvable matrix may comprise any shape.
  • the solid dissolvable matrix is in a disc shape.
  • the disc may have a diameter of 0.5-4, 0.5-3, 0.5-3, 1-3, 1-2, 1.5-3.5 or 1.5-2.5 inches and has a thickness of 100-2000, 100-5000, 100-1000, 100-500, 200-700, 300-700, 400-500, 400-1000, 500-2000, 750-2000, 800-2000, or 1200-5000 microns.
  • the disc has a diameter of 0.5-4, 0.5-3, 0.5-3, 1-3, 1-2, 1.5-3.5 or 1.5-2.5 inches.
  • the disc has a diameter of about 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, or about 3 inches. In some instances, the disc has a diameter of no more than 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, or no more than 3 inches. In some instances, the disc has a thickness of 100-2000, 100-5000, 100-1000, 100-500, 200-700, 300-700, 400- 500, 400-1000, 500-2000, 750-2000, 800-2000, or 1200-5000 microns.
  • the disc has athickness of about 100, 150, 200, 250, 300, 350, 400, 450, 500, or about 700 microns.
  • Dissolvable matrices may comprise a variety of weights. In some instances, the dissolvable matrix is at least 100, 200, 500, 800, 1000, 2000, or 5000 mg (in total, i.e., including active ingredients and excipients). In some instances, the dissolvable matrix is about 500-800, 100-800, 50-200, 100-500, 200-800, 500-1000, or 500-1500 mg. In some instances, a dissolvable matrix weighs from about 1 gram to about 2 grams, e.g., about 1.4 or 1.6 grams.
  • the dissolvable matrix is about 1 microgram or more, e.g., 1 pg, 2 pg, 3 pg, 4 pg, 5 pg, 6 pg, 7 pg, 8 pg, 9 pg, 10 pg, 20 pg, 30 pg profession 40 pg, 50 pg, 60 pg, 70 pg, 80 pg, 90 pg, 100 pg, 200 pg, 300 pg, 400 pg, 500 pg, 600 pg, 700 pg, 800 pg, 900 pg, 1000 pg or more.
  • the dissolvable matrix is about 1 milligram or more, e.g., 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 20 mg, 30 mghyroid 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 200 mg, 300 mg, 400 mg, or 500 mg.
  • each matrix is in some instances tailored depending upon its intended use, its packaging, and/or its shipping method.
  • the matrix is printed in a rectangular shape, such that the matrix is rectangular and capable of being positioned within a box for flat shipping.
  • the matrix is printed in a circular shape, such that the matrix is circular and capable of packaged in a tube.
  • Circular dissolvable matrices are particularly suitable for being added to beverages in a glass or another circular container for dissolution.
  • a dissolvable matrix described herein is placed in packaging for transport or commercial sale.
  • the packaging is substantially air and water tight.
  • packaging further comprises an ingredient label.
  • packaging further comprises instructions for use.
  • the dissolvable matrix may be arranged in various dispensing configurations.
  • a dispensing configuration comprises continuous tape with or without perforations for tearing.
  • the continuous tape arrangement of the dissolvable matrix is placed in a tape dispenser type device, where a portion of the strip may be torn off with the assistance of a cutting blade.
  • a support substrate such as release paper in some instances supports and or encloses the dissolvable matrix.
  • the dissolvable matrix is printed on a release paper in the form of dots, small particles, granules, or the like. The dissolvable matrix is then be removed from the release paper.
  • the dissolvable matrix may be stored in a dispenser such as a dispenser with openings similar manner to that of a salt shaker.
  • a dispenser such as a dispenser with openings similar manner to that of a salt shaker.
  • Other dispensing configurations include but are not limited to stacking the dissolvable matrix on top of each, such as similar to Pez® candy from a Pez® candy dispenser, or packaging the dissolvable matrix in a pouch or sealed packaging, similar to an individual bandage.
  • Packaging for dispensing in some instances is printed and/or individualized, for example, with a person's name, companies name, or company logo.
  • methods comprising promoting or maintaining a physical status or condition of a subject.
  • methods comprise administering a dissolvable composition described herein.
  • a dissolvable composition is administered wherein the dissolvable composition comprises one or more active ingredients.
  • the active ingredient comprises a nutraceutical.
  • a method for promoting a condition of a subject comprises administering a dissolvable composition described herein.
  • a method of maintaining a physical status or a condition of a subject comprises administering a dissolvable composition described herein.
  • the condition comprises youthfulness appearance (healthy skin and cell membranes, softness, wrinkle reduction, regulation of oil production, regulation of hydration, reduction of hyperkeratinization of hair follicles, reduction of premature aging, reduction of acne, and reduction or prevention of sun damage), reduced depression or anxiety (or associated symptoms such as sadness, lethargy, or general loss of interest in life), eye health (healthy visual acuity, night vision, and health of specific eye structures, such as retina or macula, tear production, or other eye-related health issue), cognitive function (intelligence, improved communication and social skills, decreasing hyperactivity, impulsiveness, restlessness, aggression, reduction in mood swings, reducing age-related mental decline, or related diseases), digestive health (microbiome composition, regularity, reduction in bloating) cardiovascular health (reduction in triglycerides, blood pressure, blood clots, arterial plaques, inflammation, regulation of cholesterol levels, such as by increasing levels of high-density lipids), healthy immune system (lowering the risk or symptoms of diseases such as
  • the condition comprises healthy sleep. In some instances, the condition comprises performance. In some instances, the condition comprises digestive health. In some instances, the condition comprises a healthy immune system.
  • the matrices herein can be used to promote or maintain a healthy brain, healthy mood, cardiovascular health, blood sugar, glucose metabolism, weight management or optimal weight, healthy aging, reduction of oxidative stress, a healthy inflammatory response (e.g., in the central nervous system), and/or reduction of lipid accumulation in fat cells. Also, they can be used to promote higher quality and/or quantity sleep.
  • a method comprises administering a dissolvable matrix herein for promoting a condition of a subject, wherein the condition comprises a healthy brain, healthy mood, cardiovascular health, blood sugar, glucose metabolism, weight management or optimal weight, healthy aging, reduction of oxidative stress, a healthy inflammatory response (c.g, in the central nervous system), and/or reduction of lipid accumulation in fat cells. Also, they can be used to promote higher quality and/or quantity sleep.
  • a method comprises administering a dissolvable matrix herein for maintaining a condition of a subject, wherein the condition comprises a healthy brain, healthy mood, cardiovascular health, blood sugar, glucose metabolism, weight management or optimal weight, healthy aging, reduction of oxidative stress, a healthy inflammatory response (e.g., in the central nervous system), and/or reduction of lipid accumulation in fat cells.
  • dissolvable matrices can be used to promote higher quality and/or quantity sleep.
  • the dissolvable matrices may be used sublingually, orally, added to a food or beverage item, etc., depending upon their configuration. For instance, dissolvable matrices which are configured to dissolve/disperse easily may be used sublingually, whereas a dissolvable matrix which is configured to dissolve may be used within a beverage item.
  • dissolvable matrices which are configured to dissolve/disperse easily may be used sublingually, whereas a dissolvable matrix which is configured to dissolve may be used within a beverage item.
  • the foregoing examples are in no way limiting, as slow dissolving/dispersing dissolvable matrices may be used in a beverage and a fast dissolving/dispersing dissolvable matrix may be used orally.
  • the beverage in some instances includes but is not limited to juice, water, tea, milk, coffee, fermented beverages (beer, wine, kombucha), soda, or other solvent.
  • the dissolvable matrix may be used in various applications that may benefit from a supplement.
  • the dissolvable matrix is added to a food or beverage, such as a tea bag, a coffee pod, and the like.
  • a supplement from the printed composition within the tea bag and/or coffee pod is released in the tea and/or coffee.
  • a dissolvable matrix disclosed herein can be produced using one or more of the following manufacturing methodologies.
  • a first method for making a dissolvable matrix comprises 1) mixing one or more active ingredients and at least one excipient in a solvent to produce a mixture, 2) printing the mixture, and 3) curing the mixture.
  • the method can further comprise the step of shaping the mixture.
  • a plurality of active ingredients and excipients are combined with a liquid (e.g., purified water) to create a homogenous liquid composition that is capable of being printed.
  • Ingredients e.g., active ingredients and excipients
  • solvents e.g., purified water
  • the liquid composition is mixed to achieve a desired initial viscosity.
  • An initial viscosity is measured in cP (millipascal-second).
  • An initial viscosity may be 1000-25000, 2000-25000, 5000-25000, 8000-25000, 1000-12000, 4000-15000 5000-20000, or 2000-15000 cP.
  • a mixture provided herein has an initial viscosity of 5000-13000 cP, 7000-20000 cP, or 3000-10000 cP.
  • the dissolvable matrix can be printed using any number of printing techniques.
  • the matrix may be made by screening printing, rotary screen printing, flexography, offset gravure, ink jet, bubble jet, dry toner, ribbon transfer, powder coating, spray coating, roll coating, reverse roll coating, slot die coating, hot and/or cold laminating, knife coating, sintering, padding, or curtain coating, and the like.
  • printing techniques are understood to cover coating techniques.
  • the matrix is made using printing.
  • Curing is notable in that a dissolvable acquires its final, solid shape after curing. In other words, during curing volatile and liquid components of the printed mixture are evaporated, dried, or the like, leaving a shelf-stable, solid dissolvable matrix. Curing can occur at room temperature up to about 95 °C.
  • Curing steps may be performed at a specific temperature or range of temperatures, for a period of time.
  • a curing step is performed for a time until the dissolvable matrix reaches a desired water content (e.g., dried), e.g., a water content of less than 10%, 8%, 7%, 6%, 5%, 4%, 3%, or less than 2% (w/w).
  • a matrix may be cured at a temperature of 50- 90, 50-70, 60-80, 65-90, 65-80, 70-80, 70-85, 60-70, or 65-75 °C.
  • a matrix may be dried for at least 1, 2, 5, 8, 10, or more than 10 hours, e.g., 0.5-5, 1-5, 2-5, 2-10, 3-15, 5-24, or 8-16 hours.
  • the moisture content may be measured by water balance.
  • Stencils of different sizes and shapes may be used to produce dissolvable matrices of a desired size and shape.
  • the stencil gauge is 10-25, 12-15, 12-22, 13-18, 15-20, or 14-20. In some instances, the stencil gauge is 14. In some instances, the stencil gauge is 20. In some instances, the stencil gauge is 14.
  • shaping comprises use of a blade and/or other cutting instrument to achieve a desired shape and size
  • indicia may include the identification codes, such as spatial codes, QR codes, bar codes, identification numbers, or other such indicia which can be used to identifying, track, and/or provide information.
  • identification codes such as spatial codes, QR codes, bar codes, identification numbers, or other such indicia which can be used to identifying, track, and/or provide information.
  • These indicia and decorative designs may be ink-jet or flexographic printed directly onto the dissolvable matrix.
  • the ink used may be culturally- and/or dietary-acceptable inks, e.g., vegetarian, vegan, halal, and kosher.
  • any other printing technique may be used, such as screening printing, rotary screen printing, flexography, offset gravure, ink jet, bubble jet, dry toner, ribbon transfer, powder coating, spray coating, roll coating, reverse roll coating, slot die coating, hot and/or cold laminating, knife coating, sintering, padding, curtain coating, and the like.
  • printing techniques are understood to cover coating techniques.
  • the ink may be aqueous or solvent based.
  • the ink may be ultraviolet (UV) curable, electron beam (EB) curable, thermally curable, cold curable, ambient catalyzed, ambient crosslinked, and the like.
  • the ink may be edible and/or dissolvable based on the desired application.
  • FIG. 1 illustrates a method for determining matrix classes based on an active ingredient or combinations of active ingredients.
  • each matrix type e.g., 1, la, 2, 2a, as disclosed herein
  • each matrix type is associated, at least, with a specific set and/or concentration of excipients.
  • a class 1 dissolvable matrix comprises one or more active ingredients in which the active ingredient or combination of active ingredients is water soluble and not hydroscopic.
  • Class 1 matrices comprise active ingredients, pore-creating excipients, pore-size modifying excipients, and emulsifiers.
  • An illustrative class 1 matrix comprises blueberry powder, green tea extract, pomegranate powder, and a bacteriophage component.
  • class 1 matrix comprises one or more B vitamins, e.g., riboflavin-5-phosphate, methylcobalamin, L-methyltetrahydrofolate (L-MTHF) calcium salt, pyridoxal-5-phosphate (P5P), and thiamine HC1.
  • B vitamins e.g., riboflavin-5-phosphate, methylcobalamin, L-methyltetrahydrofolate (L-MTHF) calcium salt, pyridoxal-5-phosphate (P5P), and thiamine HC1.
  • the pore-creating excipient is cellulose powder and/or quillaja extract.
  • a class la dissolvable matrix comprises one or more active ingredients in which the active ingredient or combination of active ingredients is water soluble and is hydroscopic.
  • Class la matrices comprise active ingredients, pore-creating excipients, pore-size modifying excipients, and mineral ions/mineral ion donors, and, optionally, hygroscopicity modifiers.
  • One illustrative class la matrix comprises blueberry powder, green tea extract, pomegranate powder, and a bacteriophage component as active ingredients.
  • Other illustrative class la matrices comprise Other illustrative class la matrices comprise Other illustrative class la matrices comprise mango leaf extract, methylcobalamin, L-methyltetrahydrofolate methyltetrahydrofolate Ca, and Pyridoxal-5- Phosphate as active ingredients.
  • the pore-creating excipients are cellulose powder and quillaja extract.
  • the hygroscopicity modifier, when present, is MCT oil powder.
  • the pore-size modifying excipient is microcrystalline cellulose.
  • a class 2 dissolvable matrix comprises one or more active ingredients in which the active ingredient or combination of active ingredients is water insoluble and is lipophilic.
  • Class 2 matrices comprise active ingredients, pore-creating excipients, pore-size modifying excipients, and emulsifiers.
  • One illustrative class 2 matrix comprises chamomile extract, L-Theanine, and melatonin as active ingredients.
  • the pore-creating excipients are cellulose powder and quillaja extract.
  • the pore-size modifying excipient is oat fiber.
  • the emulsifier is carboxymethyl cellulose gum (CMC gum).
  • a class 2a dissolvable matrix comprises one or more active ingredients in which the active ingredient or combination of active ingredients is water insoluble and is not lipophilic, and one of the active ingredients comprises lecithin.
  • Class 2a matrices comprise active ingredients (at least one of which is a lecithin), pore-creating excipients, pore-size modifying excipients, and mineral ions/mineral ion donors.
  • active ingredients at least one of which is a lecithin
  • pore-creating excipients e.g., ascorbic acid (vitamin C)
  • a zinc salt e.g., zinc picolinate
  • the pore-creating excipients are cellulose powder and quillaja extract.
  • the pore-size modifying excipient is tapioca starch.
  • the mineral ions/mineral ion donors is calcium carbonate.
  • An exemplary class 3 dissolvable matrix comprises one or more active ingredients.
  • Class 3 matrices may comprise active ingredients, pore-creating excipients, poresize modifying excipients, and mineral ions/mineral ion donors, and, optionally, hygroscopicity modifiers.
  • One illustrative class 3 matrix comprises blueberry powder, green tea extract, pomegranate powder, and a bacteriophage component as active ingredients.
  • Other illustrative class 3 matrices comprise multiple vitamins, magnesiums, iodine, zinc salts, and docosahexaenoic acid (DHA) as active ingredients.
  • the pore-creating excipients may be cellulose powder and quillaja extract.
  • the hygroscopicity modifier when present, may be gum acacia.
  • Embodiment 1 A method for manufacturing a dissolvable sheet, the method comprising: mixing one or more scaffolding agents, one or more blowing agents, one or more active ingredients, one or more phospholipids, and water to form a mixture having a viscosity from 4,000 to 15,000 cP; depositing the mixture onto a surface having a predefined shape; and removing water from the deposited mixture to form a dissolvable sheet having a water content of less than 4% (w/w).
  • Embodiment 2 The method of Embodiment 1, wherein depositing the mixture comprises depositing the mixture onto a stencil.
  • Embodiment 3 The method of Embodiment 2, wherein the stencil has a fillable height of from 0.7 mm to 4.0 mm.
  • Embodiment 4 The method of any one of Embodiments 1-3, wherein the dissolvable sheet has a thickness of between 100 microns and 3000 microns, such as between 300 microns and 3000 microns or between 500 microns and 2000 microns.
  • Embodiment 5 The method of any one of Embodiments 1-4, wherein removing the water from the deposited mixture comprises heating the deposited mixture.
  • Embodiment 6 The method of Embodiment 5, wherein the deposited mixture is heated by exposure to a temperature of between 45 and 110 degrees Celsius.
  • Embodiment 7 The method of Embodiment 5 or 6, wherein the deposited mixture is heated for between 15 and 180 minutes.
  • Embodiment 8 The method of any one of Embodiments 1-7, wherein depositing the mixture onto the surface comprises delivering the material via a printer with a squeegee pressure of 1-100 kgf.
  • Embodiment 9 The method of any one of Embodiments 1-8, wherein the one or more phospholipids are selected from Phosphatidylcholine (PC), Lyso-Phosphatidylcholine (LPC), Phosphatidylinositol (PI), Phosphatidylethanolamine (PE), Lyso-Phosphatidylethanolamine (LPE), and Phosphatidic Acid (PA).
  • PC Phosphatidylcholine
  • LPC Lyso-Phosphatidylcholine
  • PI Phosphatidylinositol
  • PE Phosphatidylethanolamine
  • LPE Lyso-Phosphatidylethanolamine
  • PA Phosphatidic Acid
  • Embodiment 10 The method of Embodiment 9, wherein the one or more phospholipids comprise from about 19% to about 23% Phosphatidylcholine (PC), from about 15% to about 22% Phosphatidylinositol (PI), from about 6 to about 13% Phosphatidylethanolamine (PE), and from about 2% to about 6% Phosphatidic Acid (PA).
  • PC Phosphatidylcholine
  • PI Phosphatidylinositol
  • PE Phosphatidylethanolamine
  • PA Phosphatidic Acid
  • Embodiment 11 The method of Embodiment 10, wherein the one or more phospholipids comprise fatty acid chains selected from Palmitic acid (C16:0), Stearic acid (C18:0), Oleic acid (C18: l), Linoleic acid (C18:2), and Linolenic acid (C18:3).
  • Palmitic acid C16:0
  • Stearic acid C18:0
  • Oleic acid C18: l
  • Linoleic acid C18:2
  • Linolenic acid C18:3
  • Embodiment 12 The method of Embodiment 11, wherein the fatty acid chains comprise from about 14% to about 18% Palmitic (C16:0), from about 3% to about 5% Stearic (Cl 8:0), from about 12% to about 14% Oleic (Cl 8: 1), from about 62% to about 66% Linoleic (C18:2), and from about 2% to about 4% Linolenic (C18:3).
  • the fatty acid chains comprise from about 14% to about 18% Palmitic (C16:0), from about 3% to about 5% Stearic (Cl 8:0), from about 12% to about 14% Oleic (Cl 8: 1), from about 62% to about 66% Linoleic (C18:2), and from about 2% to about 4% Linolenic (C18:3).
  • Embodiment 13 The method of any preceding Embodiment, wherein the dissolvable sheet comprises from about 0.01% to about 5%, (w/w) phospholipids.
  • Embodiment 14 The method of any preceding Embodiment, wherein the dissolvable sheet comprises at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, 1.00%, 1.10%,
  • Embodiment 15 The method of any one of the preceding Embodiments, wherein the one or more phospholipids is derived from lecithin.
  • Embodiment 16 The method of Embodiment 13, wherein the lecithin is obtained from soybeans (including soybean oil), grains (e.g., corn, rice, barley), peanuts (including peanut oil), wheat germ, hemp, pumpkin seed, sesame seed, rice bran, almonds, yeast, algae, plant oils (e.g., sunflower, canola, safflower, olive, coconut, rapeseed, flaxseed, sesame, and cottonseed), egg, milk, organ meat, or shellfish.
  • soybeans including soybean oil
  • grains e.g., corn, rice, barley
  • peanuts including peanut oil
  • wheat germ e.g., hemp, pumpkin seed, sesame seed, rice bran, almonds, yeast, algae
  • plant oils e.g., sunflower, canola, safflower, olive, coconut, rapeseed, flaxseed, sesame, and cottonseed
  • egg milk
  • organ meat or shellfish.
  • Embodiment 16a The method of Embodiment 15, wherein the lecithin is combined with avocado oil.
  • Embodiment 17 The method of Embodiment 14, wherein the lecithin is a de-oiled sunflower lecithin.
  • Embodiment 17a The method of Embodiment 17, wherein the de-oiled sunflower lecithin is combined with avocado oil.
  • Embodiment 18 The method of Embodiment 15, wherein the de-oiled sunflower lecithin comprise chemical and physical characteristics of one or more of acetone insoluble matter of at least 96%, toluene insoluble matter of at most 0.3%, moisture of at most 2%, acid value of at most 35 mg KOH/g, peroxide value of at most 10 meq/kg, and particle size in which 100% of particles pass through 60 mesh.
  • Embodiment 19 The method of any one of Embodiments 15-18, wherein the dissolvable sheet comprises from about 0.1% to about 10% (w/w) lecithin.
  • Embodiment 20 The method of any one of Embodiments 15-18, wherein the dissolvable sheet comprises at least about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.10%, 0.20%, 0.30%, 0.40%, 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, 1.00%,
  • Embodiment 21 The method of any one of Embodiments 15-20, wherein the dissolvable sheet comprises about 10 mg lecithin per 1.4 grams of dissolvable sheet.
  • Embodiment 21a The method of any one of Embodiments 15-20, wherein the dissolvable sheet comprises between 5 mg and 10 mg lecithin per 1.8 grams of dissolvable sheet.
  • Embodiment 22 The method of any one of the preceding Embodiments, wherein the dissolvable sheet has a dry weight from about 1 gram to about 2 grams, e.g., about 1.4 grams or 1.8 grams.
  • Embodiment 23 The method of any one of the preceding Embodiments, wherein the active ingredient is or comprises a pharmaceutical composition; a nutraceutical composition; a plant extract, an animal extract, or a fungal extract; a prebiotic; or a sleep enhancer.
  • Embodiment 24 The method of any one of the preceding Embodiments, wherein the active ingredient is or comprises blueberry powder, green tea decaffeinated extract (leaf), pomegranate polyphenol powder, Preforpro, Chamomile Extract, L-Theanine, Melatonin, Quercetin, Vitamin D3, Ascorbic Acid, Zinc Picolinate, mango extract, methyl cobalamin, 1- 5-methyltetrahydrofolate, pyridoxal-5-phosphate, or riboflavin-5-phosphate sodium.
  • the active ingredient is or comprises blueberry powder, green tea decaffeinated extract (leaf), pomegranate polyphenol powder, Preforpro, Chamomile Extract, L-Theanine, Melatonin, Quercetin, Vitamin D3, Ascorbic Acid, Zinc Picolinate, mango extract, methyl cobalamin, 1- 5-methyltetrahydrofolate, pyridoxal-5-phosphate, or riboflavin-5-phosphate sodium.
  • Embodiment 25 The method of any one of the preceding Embodiments, wherein the active ingredient is or comprises one or more of Lutein (from Lutemax 2020 (Tagetes erecta)), Zeaxanthin (from Lutemax 2020 (Tagetes erecta)), Vitamin A (120 mcg RAE as Beta Carotene), Vitamin C (as Ascorbic Acid), Vitamin D (as Healthy Vitamin D3) (800 IU), Vitamin E (as d- Alpha Tocopherol from Mixed Tocopherols), Vitamin K2 (as MK-7), Zinc (as Zinc Bisglyccommune), Riboflavin (as Riboflavin 5' - Phosphate Sodium), Vitamin B6 (as Pyridoxal 5'-Phosphate), Folate (as L-5-Methyltetrahydrofolate), Vitamin B12 (as Methylcobalamin), Choline (as Choline Citrate), iod
  • Embodiment 26 The method of Embodiment 21, wherein the active ingredient, when present, comprises Lutein in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Zeaxanthin in an amount of about 0.2 mg per 1.4 g dry dissolvable matrix, Vitamin A in an amount of about 0.12 mg per 1.4 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.4 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 0.02 mg per 1.4 g dry dissolvable matrix, Vitamin E in an amount of about 7.5 mg per 1.4 g dry dissolvable matrix, Vitamin K2 in an amount of about 0.05 mg per 1.4 g dry dissolvable matrix, Zinc in an amount of about 5 mg per 1.4 g dry dissolvable matrix, Riboflavin in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Vitamin B6 in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Folate
  • Embodiment 26a The method of Embodiment 21 , wherein the active ingredient, when present, comprises Lutein in an amount of about 1 mg per 1.8 g dry dissolvable matrix, zeaxanthin in an amount of about 0.20 mg per 1.8 g dry dissolvable matrix, Vitamin A in an amount of about 1.34 mg per 1.8 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.8 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 0.02 mg per 1.8 g dry dissolvable matrix, Vitamin E in an amount of about 7.5 mg per 1.8 g dry dissolvable matrix, Vitamin K2 in an amount of about 0.05 mg per 1.8 g dry dissolvable matrix, Zinc in an amount of about 5 mg per 1.8 g dry dissolvable matrix, Riboflavin in an amount of about 1 mg per 1.8 g dry dissolvable matrix, Vitamin B6 in an amount of about 1 mg per 1.8 g dry dissolvable
  • Embodiment 27 The method of any preceding Embodiment, wherein the one or more active ingredients are from about 0.05% to about 70% of the dissolvable sheet by weight, e.g., from about 0.05% to about 5%, from about 1% to about 30%, from about 5% to about 30%, or from about 1% to about 50% of the dissolvable sheet by weight.
  • Embodiment 28 The method of any preceding Embodiment, wherein the at least one excipient comprises powdered cellulose or quillaja extract.
  • Embodiment 29 The method of any preceding Embodiment, wherein the at least one excipient comprises powdered cellulose and quillaja extract.
  • Embodiment 30 The method of Embodiment 28 or Embodiment 29, wherein the powdered cellulose is 10-35% (w/w).
  • Embodiment 30a The method of Embodiment 28 or Embodiment 29, wherein the powdered cellulose is 5-10% (w/w) relative to the dissolvable sheet.
  • Embodiment 31 The method of any one of Embodiments 28-30, wherein the quillaja extract is 0.5-10% (w/w).
  • Embodiment 32 The method of any one of Embodiments 28-31, wherein the at least one excipient is configured for pore size/distribution modification and/or emulsifier stabilization.
  • Embodiment 33 The method of Embodiment 32, wherein the excipient has a D50 of 50-150 microns.
  • Embodiment 34 The method of any preceding Embodiment, wherein the excipient comprises microcrystalline cellulose.
  • Embodiment 35 The method of any preceding Embodiment, wherein the excipient comprises tapioca starch, microcrystalline cellulose, or Oat fiber.
  • Embodiment 36 The method of any preceding Embodiment, wherein the excipient comprises tapioca starch or Oat fiber.
  • Embodiment 36a The method of embodiment 35 or 36, wherein the excipient comprises Oat fiber.
  • Embodiment 36b The method of embodiment 36a, wherein the dissolvable sheet is 5-20% Oat fiber (w/w).
  • Embodiment 37 The method of any one of Embodiments 34-36, wherein the microcrystalline cellulose is 5-15% (w/w).
  • Embodiment 38 The method of any preceding Embodiment, wherein the at least one excipient comprises an emulsifier.
  • Embodiment 39 The method of Embodiment 38, wherein the emulsifier comprises carboxymethyl cellulose (CMC) gum.
  • Embodiment 39a The method of Embodiment 38, wherein the emulsifier comprises gum acacia.
  • Embodiment 40 The method of any preceding Embodiment, wherein the at least one excipient comprises a hygroscopicity modifier.
  • Embodiment 41 The method of Embodiment 40, wherein the hygroscopicity modifier comprises medium chain triglycerides (MCTs).
  • MCTs medium chain triglycerides
  • Embodiment 42 The method of Embodiment 41, wherein the MCTs are 1-5% (w/w).
  • Embodiment 43 The method of any preceding Embodiment, wherein the at least one excipient comprises a mineral ion donor.
  • Embodiment 44 The method of Embodiment 43, wherein the mineral ion donor comprises a calcium salt, e.g., calcium carbonate.
  • a calcium salt e.g., calcium carbonate.
  • Embodiment 44a The method of Embodiment 43, wherein the mineral ion donor comprises a magnesium salt, e.g., magnesium malate or magnesium citrate.
  • a magnesium salt e.g., magnesium malate or magnesium citrate.
  • Embodiment 45 The method of Embodiment 43 or Embodiment 44, wherein the mineral ion donor is 1-10% (w/w).
  • Embodiment 46 The method of any preceding Embodiment, wherein the at least one excipient comprises a pullulan.
  • Embodiment 47 The method of Embodiment 46, wherein the pullulan is 1-5% (w/w).
  • Embodiment 48 The method of Embodiment 46 or Embodiment 47, wherein the amount of pullulan in a dissolvable sheet is less than the amount of pullulan in a dissolvable sheet that lacks one or more phospholipids.
  • Embodiment 49 The method of Embodiment 48, wherein the amount of pullulan in a dissolvable sheet is from about 10% to about 15%, e.g., 13%, less than the amount of pullulan in a dissolvable sheet that lacks one or more phospholipids.
  • Embodiment 50 The method of Embodiment 49, wherein a phospholipid-containing matrix comprises less than 3.4% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.8% pullulan, a phospholipid-containing matrix comprises less than 3.2% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.5% pullulan, a phospholipid-containing matrix comprises less than 3.7% pullulan whereas an equivalent matrix yet lacking phospholipids comprises more than 4% pullulan, a phospholipid-containing matrix comprises less than 3.2% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.5% pullulan, a phospholipid-containing matrix comprises less than 2.1% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 2.3% pullulan.
  • Embodiment 51 The method of any preceding Embodiment, wherein the at least one excipient comprises a glycerin.
  • Embodiment 52 The method of Embodiment 51, wherein the glycerin is 2-15% (w/w).
  • Embodiment 53 The method of any preceding Embodiment, wherein the at least one excipient comprises plant fibers, oils, gums, or collagen.
  • Embodiment 54 The method of any one of the preceding Embodiments, wherein at least 80%, at least 90%, or at least 95% by mass of the dissolvable sheet dissolves in about 15 °C water in about 10 to 30 seconds without agitation.
  • Embodiment 55 The method of any one of the preceding Embodiments, wherein a void volume is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, or at least about 70% (v/v) relative to the dissolvable sheet.
  • Embodiment 56 The method of any one of the preceding Embodiments, wherein a void volume is about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, or about 70% (v/v) relative to the dissolvable sheet.
  • Embodiment 57 The method of Embodiment 56, wherein a void volume is about 33% (v/v) relative to the dissolvable sheet.
  • Embodiment 58 The method of any one of the preceding Embodiments, wherein dissolvable sheet comprises a balance of pore size, pore number, and pore distribution that provides desirable tensile strength, dissolution speed, and moisture transfer rates.
  • Embodiment 59 The method of Embodiment 58, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.01 to about 0.04 mm 2 .
  • Embodiment 60 The method of Embodiment 58, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.02 to about 0.03 mm 2 .
  • Embodiment 61 The method of Embodiment 58 or Embodiment 60, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.026 mm 2 .
  • Embodiment 62 The method of Embodiments 58, wherein the median pore area on the bottom surface of the dissolvable sheet is from about 0.01 to about 0.04 mm 2 .
  • Embodiment 63 The method of Embodiment 62, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.015 to about 0.025 mm 2 .
  • Embodiment 64 The method of Embodiment 62 or Embodiment 63, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.020 mm 2 .
  • Embodiment 65 The method of any one of Embodiments 58-64, wherein the average number of pores per area of the bottom surface of the dissolvable sheet is from about 15 to about 45 pores/mm 2 .
  • Embodiment 66 The method of any one of Embodiments 58-65, wherein the average number of pores per area of the bottom surface of the dissolvable sheet is from about 25 to about 40 pores/mm 2 .
  • Embodiment 67 The method of any one of Embodiments 58-66, wherein the average number of pores per area of the bottom surface of the dissolvable sheet is from about 30 to about 35 pores/mm 2 .
  • Embodiment 68 The method of any one of Embodiments 58-67, wherein the average number of pores per area of the bottom surface of the dissolvable sheet is about 34 pores/mm 2 .
  • Embodiment 69 The method of any one of the preceding Embodiments, wherein the dissolvable sheet is shelf stable.
  • Embodiment 70 A dissolvable sheet formed by the method of any one of Embodiments 1-69.
  • Embodiment 71 A dissolvable sheet comprising one or more scaffolding agents, one or more blowing agents, one or more active ingredients, one or more phospholipids, and having a water content of less than 4% (w/w).
  • Embodiment 72 The dissolvable sheet of Embodiment 71, wherein the dissolvable sheet has a thickness of between 100 microns and 3000 microns, such as between 300 microns and 3000 microns or between 500 microns and 2000 microns.
  • Embodiment 73 The dissolvable sheet of Embodiment 71 or Embodiment 72, wherein the one or more phospholipids are selected from Phosphatidylcholine (PC), Lyso- Phosphatidylcholine (LPC), Phosphatidylinositol (PI), Phosphatidylethanolamine (PE), Lyso- Phosphatidylethanolamine (LPE), and Phosphatidic Acid (PA).
  • PC Phosphatidylcholine
  • LPC Lyso- Phosphatidylcholine
  • PI Phosphatidylinositol
  • PE Phosphatidylethanolamine
  • LPE Lyso- Phosphatidylethanolamine
  • PA Phosphatidic Acid
  • Embodiment 74 The dissolvable sheet of Embodiment 73, wherein the one or more phospholipids comprise from about 19% to about 23% Phosphatidylcholine (PC), from about 15% to about 22% Phosphatidylinositol (PI), from about 6 to about 13% Phosphatidylethanolamine (PE), and from about 2% to about 6% Phosphatidic Acid (PA).
  • PC Phosphatidylcholine
  • PI Phosphatidylinositol
  • PE Phosphatidylethanolamine
  • PA Phosphatidic Acid
  • Embodiment 75 The dissolvable sheet of Embodiment 74, wherein the one or more phospholipids comprise fatty acid chains selected from Palmitic acid (C16:0), Stearic acid (C18:0), Oleic acid (C18: l), Linoleic acid (C18:2), and Linolenic acid (C18:3).
  • Palmitic acid C16:0
  • Stearic acid C18:0
  • Oleic acid C18: l
  • Linoleic acid C18:2
  • Linolenic acid C18:3
  • Embodiment 76 The dissolvable sheet of Embodiment 75, wherein the fatty acid chains comprise from about 14% to about 18% Palmitic (C16:0), from about 3% to about 5% Stearic (Cl 8:0), from about 12% to about 14% Oleic (Cl 8: 1), from about 62% to about 66% Linoleic (C18:2), and from about 2% to about 4% Linolenic (C18:3).
  • Embodiment 77 The dissolvable sheet of any one of Embodiments 71-76, wherein the dissolvable sheet comprises at least 1%, 2%, 5%, 8%, 10%, 15%, 20%, or 30%, (w/w) phospholipids.
  • Embodiment 78 The dissolvable sheet of any one of Embodiments 71-77, wherein the dissolvable sheet comprises at least 0.05%, 0.1%, 0.2%, 0.3%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, 6%, 8%, or at least 10% (w/w) phospholipids.
  • Embodiment 79 The dissolvable sheet of any one of Embodiments 71-78, wherein the one or more phospholipids is derived from lecithin.
  • Embodiment 80 The dissolvable sheet of Embodiment 77, wherein the lecithin is obtained from soybeans (including soybean oil), grains (e.g., corn, rice, barley), peanuts (including peanut oil), wheat germ, hemp, pumpkin seed, sesame seed, rice bran, almonds, yeast, algae, plant oils (e.g., sunflower, canola, safflower, olive, coconut, rapeseed, flaxseed, sesame, and cottonseed), egg, milk, organ meat, or shellfish.
  • soybeans including soybean oil
  • grains e.g., corn, rice, barley
  • peanuts including peanut oil
  • wheat germ e.g., hemp, pumpkin seed, sesame seed, rice bran, almonds, yeast, algae
  • plant oils e.g., sunflower, canola, safflower, olive, coconut, rapeseed, flaxseed, sesame, and cottonseed
  • egg milk
  • organ meat or shellfish
  • Embodiment 80a the dissolvable sheet of Embodiment 80, wherein the lecithin is combined with avocado oil.
  • Embodiment 81 The dissolvable sheet of Embodiment 80, wherein the lecithin is a de-oiled sunflower lecithin.
  • Embodiment 81a The dissolvable sheet of Embodiment 81, wherein the de-oiled sunflower lecithin is combined with avocado oil.
  • Embodiment 82 The dissolvable sheet of Embodiment 81, wherein the de-oiled sunflower lecithin comprise chemical and physical characteristics of one or more of acetone insoluble matter of at least 96%, toluene insoluble matter of at most 0.3%, moisture of at most 2%, acid value of at most 35 mg KOH/g, peroxide value of at most 10 meq/kg, and particle size in which 100% of particles pass through 60 mesh.
  • Embodiment 83 The dissolvable sheet of any one of Embodiments 71-82, wherein the dissolvable sheet comprises at least 0.05%, 0.1%, 0.2%, 0.3%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, 6%, 8%, 10%, 15%, 20%, or 30%, (w/w) lecithin..
  • Embodiment 84 The dissolvable sheet of any one of Embodiments 71-82, wherein the dissolvable sheet comprises at most 30% (w/w) lecithin.
  • Embodiment 85a The dissolvable sheet of any one of Embodiments 71-84, wherein the dissolvable sheet comprises about 10 mg lecithin per 1.4 grams of dissolvable sheet.
  • Embodiment 85 The dissolvable sheet of any one of Embodiments 71-84, wherein the dissolvable sheet comprises between 5 mg and 10 mg lecithin per 1.8 grams of dissolvable sheet.
  • Embodiment 86 The dissolvable sheet of any one of Embodiments 71-85, wherein the dissolvable sheet has a dry weight from about 1 gram to about 2 grams, e.g., about 1.4 grams.
  • Embodiment 87 The dissolvable sheet of any one of Embodiments 71-86, wherein the active ingredient is or comprises a pharmaceutical composition; a nutraceutical composition; a plant extract, an animal extract, or a fungal extract; a prebiotic; or a sleep enhancer.
  • Embodiment 88 The dissolvable sheet of any one of Embodiments 71-87, wherein the active ingredient is or comprises blueberry powder, green tea decaffeinated extract (leaf), pomegranate polyphenol powder, Preforpro, Chamomile Extract, L-Theanine, Melatonin, Quercetin, Vitamin D3, Ascorbic Acid, Zinc Picolinate, mango extract, methyl cobalamin, 1- 5-methyltetrahydrofolate, pyridoxal-5-phosphate, or riboflavin-5-phosphate sodium.
  • the active ingredient is or comprises blueberry powder, green tea decaffeinated extract (leaf), pomegranate polyphenol powder, Preforpro, Chamomile Extract, L-Theanine, Melatonin, Quercetin, Vitamin D3, Ascorbic Acid, Zinc Picolinate, mango extract, methyl cobalamin, 1- 5-methyltetrahydrofolate, pyridoxal-5-phosphate, or riboflavin-5-phosphate sodium.
  • Embodiment 89 The dissolvable sheet of any one of Embodiments 71-88, wherein the active ingredient is or comprises one or more of Lutein (from Lutemax 2020 (Tagetes erecta)), Zeaxanthin (from Lutemax 2020 (Tagetes erecta)), Vitamin A (120 mcg RAE as Beta Carotene), Vitamin C (as Ascorbic Acid), Vitamin D (as vegan Vitamin D3) (800 IU), Vitamin E (as d- Alpha Tocopherol from Mixed Tocopherols), Vitamin K2 (as MK-7), Zinc (as Zinc Bisglyccommune), Riboflavin (as Riboflavin 5' - Phosphate Sodium), Vitamin B6 (as Pyridoxal 5'-Phosphate), Folate (as L-5-Methyltetrahydrofolate), Vitamin B12 (as Methylcobalamin), Choline (as Choline Citrate),
  • Embodiment 90 The dissolvable sheet of Embodiment 89, wherein the active ingredient(s), when present, comprise Lutein in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Zeaxanthin in an amount of about 0.2 mg per 1.4 g dry dissolvable matrix, Vitamin A in an amount of about 0.12 mg per 1.4 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.4 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 0.02 mg per 1.4 g dry dissolvable matrix, Vitamin E in an amount of about 7.5 mg per 1.4 g dry dissolvable matrix, Vitamin K2 in an amount of about 0.05 mg per 1.4 g dry dissolvable matrix, Zinc in an amount of about 5 mg per 1.4 g dry dissolvable matrix, Riboflavin in an amount of about 1 mg per 1.4 g dry dissolvable matrix, Vitamin B6 in an amount of about 1 mg per 1.4 g dry
  • Embodiment 90 The dissolvable sheet of Embodiment 89, wherein the active ingredient, when present, comprises Lutein in an amount of about 10.1 mg per 1.8 g dry dissolvable matrix, Vitamin A in an amount of about 1.34 mg per 1.8 g dry dissolvable matrix, Vitamin C in an amount of about 20 mg per 1.8 g dry dissolvable matrix, Vitamin D (as Vitamin D3) (800 IU) in an amount of about 8.38 mg per 1.8 g dry dissolvable matrix, Vitamin K2 in an amount of about 5 mg per 1.8 g dry dissolvable matrix, Zinc in an amount of about 30 mg per 1.8 g dry dissolvable matrix, Riboflavin in an amount of about 1.59 mg per 1.8 g dry dissolvable matrix, Vitamin B6 in an amount of about 1.79 mg per 1.8 g dry dissolvable matrix, Folate in an amount of about 0.42 mg per 1.8 g dry dissolvable matrix, Vitamin B12 in an amount of about 0.01 mg per 1.8 g dry dissolvable matrix, Vitamin
  • Embodiment 91 The dissolvable sheet of any one of Embodiments 71-90, wherein the one or more active ingredients are from about 0.05% to about 70% of the dissolvable sheet by weight, e.g., from about 0.05% to about 5%, from about 1% to about 30%, from about 5% to about 30%, or from about 1% to about 50% of the dissolvable sheet by weight.
  • Embodiment 92 The dissolvable sheet of any one of Embodiments 71-91, wherein the at least one excipient comprises powdered cellulose or quillaja extract.
  • Embodiment 93 The dissolvable sheet of any one of Embodiments 71-92, wherein the at least one excipient comprises powdered cellulose and quillaja extract.
  • Embodiment 94 The dissolvable sheet of Embodiment 92 or Embodiment 93, wherein the powdered cellulose is 10-35% (w/w).
  • Embodiment 94a The dissolvable sheet of Embodiment 92 or Embodiment 93, wherein the dissolvable sheet is 5-10% powdered cellulose (w/w).
  • Embodiment 95 The dissolvable sheet of any one of Embodiments 92-94, wherein the quillaja extract is 0.5-10% (w/w).
  • Embodiment 96 The dissolvable sheet of any one of Embodiments 91-95, wherein the at least one excipient is configured for pore size/distribution modification and/or emulsifier stabilization.
  • Embodiment 97 The dissolvable sheet of Embodiment 96, wherein the excipient has a D50 of 50-150 microns.
  • Embodiment 98 The dissolvable sheet of any one of Embodiments 71-97, wherein the excipient comprises microcrystalline cellulose.
  • Embodiment 99 The dissolvable sheet of any one of Embodiments 71-98, wherein the excipient comprises tapioca starch, microcrystalline cellulose, or Oat fiber.
  • Embodiment 100 The dissolvable sheet of any one of Embodiments 71-99, wherein the excipient comprises tapioca starch or Oat fiber.
  • Embodiment 100a The dissolvable sheet of embodiment 99 or 100, wherein the excipient comprises Oat fiber.
  • Embodiment 100b The dissolvable sheet of embodiment 100a, wherein the dissolvable sheet is 5-20% Oat fiber (w/w).
  • Embodiment 101 The dissolvable sheet of any one of Embodiments 98-100, wherein the microcrystalline cellulose is 5-15% (w/w).
  • Embodiment 102 The dissolvable sheet of any one of Embodiments 71-101, wherein the at least one excipient comprises an emulsifier.
  • Embodiment 103 The dissolvable sheet of Embodiment 102, wherein the emulsifier comprises carboxymethyl cellulose (CMC) gum.
  • CMC carboxymethyl cellulose
  • Embodiment 103a The dissolvable sheet of Embodiment 102, wherein the emulsifier comprises gum acacia.
  • Embodiment 104 The dissolvable sheet of any one of Embodiments 71-103, wherein the at least one excipient comprises a hygroscopicity modifier.
  • Embodiment 105 The dissolvable sheet of Embodiment 104, wherein the hygroscopicity modifier comprises medium chain triglycerides (MCTs).
  • MCTs medium chain triglycerides
  • Embodiment 106 The dissolvable sheet of Embodiment 105, wherein the MCTs are 1-5% (w/w).
  • Embodiment 107 The dissolvable sheet of any one of Embodiments 71-106, wherein the at least one excipient comprises a mineral ion donor.
  • Embodiment 108 The dissolvable sheet of Embodiment 107, wherein the mineral ion donor comprises a calcium salt, e.g., calcium carbonate.
  • Embodiment 108a The dissolvable of Embodiment 107, wherein the mineral ion donor comprises a magnesium salt, e.g., magnesium malate or magnesium citrate.
  • Embodiment 109 The dissolvable sheet of Embodiment 107 or Embodiment 108, wherein the mineral ion donor is 1-10% (w/w).
  • Embodiment 110 The dissolvable sheet of any one of Embodiments 71-109, wherein the at least one excipient comprises a pullulan.
  • Embodiment 111 The dissolvable sheet of Embodiment 110, wherein the pullulan is
  • Embodiment 112 The dissolvable sheet of Embodiment 110 or Embodiment 111, wherein the amount of pullulan in a dissolvable sheet is less than the amount of pullulan in a dissolvable sheet that lacks one or more phospholipids.
  • Embodiment 113 The dissolvable sheet of Embodiment 112, wherein the amount of pullulan in a dissolvable sheet is from about 10% to about 15%, e.g., 13%, less than the amount of pullulan in a dissolvable sheet that lacks one or more phospholipids.
  • Embodiment 114 The dissolvable sheet of Embodiment 113, wherein a phospholipidcontaining matrix comprises less than 3.4% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.8% pullulan, a phospholipid-containing matrix comprises less than 3.2% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.5% pullulan, a phospholipid-containing matrix comprises less than 3.7% pullulan whereas an equivalent matrix yet lacking phospholipids comprises more than 4% pullulan, a phospholipid-containing matrix comprises less than 3.2% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 3.5% pullulan, a phospholipid-containing matrix comprises less than 2.1% pullulan whereas an equivalent matrix yet lacking phospholipids comprise more than 2.3% pullulan.
  • Embodiment 115 The dissolvable sheet of any one of Embodiments 71-114, wherein the at least one excipient comprises a glycerin.
  • Embodiment 116 The dissolvable sheet of Embodiment 115, wherein the glycerin is
  • Embodiment 117 The dissolvable sheet of any one of Embodiments 71-116, wherein the at least one excipient comprises plant fibers, oils, gums, or collagen.
  • Embodiment 118 The dissolvable sheet of any one of Embodiments 71-117, wherein at least 80%, at least 90%, or at least 95% by mass of the dissolvable sheet dissolves in about 15 °C water in about 10 to 30 seconds without agitation.
  • Embodiment 119 The dissolvable sheet of any one of Embodiments 71-118, wherein a void volume is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, or at least about 70% (v/v) relative to the dissolvable sheet.
  • Embodiment 120 The dissolvable sheet of any one of Embodiments 71-119, wherein a void volume is about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, or about 70% (v/v) relative to the dissolvable sheet.
  • Embodiment 121 The dissolvable sheet of Embodiment 120, wherein a void volume is about 33% (v/v) relative to the dissolvable sheet.
  • Embodiment 122 The dissolvable sheet of any one of Embodiments 71-121, wherein dissolvable sheet comprises a balance of pore size, pore number, and pore distribution that provides desirable tensile strength, dissolution speed, and moisture transfer rates.
  • Embodiment 123 The dissolvable sheet of Embodiment 122, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.01 to about 0.04 mm 2 .
  • Embodiment 124 The dissolvable sheet of Embodiment 122, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.02 to about 0.03 mm 2 .
  • Embodiment 125 The dissolvable sheet of Embodiment 123 or Embodiment 124, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.026 mm 2.
  • Embodiment 126 The dissolvable sheet of Embodiments 122, wherein the median pore area on the bottom surface of the dissolvable sheet is from about 0.01 to about 0.04 mm 2 .
  • Embodiment 127 The dissolvable sheet of Embodiment 126, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.015 to about 0.025 mm 2 .
  • Embodiment 128 The dissolvable sheet of Embodiment 126 or Embodiment 127, wherein the mean pore area on the bottom surface of the dissolvable sheet is from about 0.020 mm 2.
  • Embodiment 129 The dissolvable sheet of any one of Embodiments 122-128, wherein the average number of pores per area of the bottom surface of the dissolvable sheet is from about 15 to about 45 pores/mm 2 .
  • Embodiment 130 The dissolvable sheet of any one of Embodiments 122-129, wherein the average number of pores per area of the bottom surface of the dissolvable sheet is from about 25 to about 40 pores/mm 2 .
  • Embodiment 131 The dissolvable sheet of any one of Embodiments 122-130, wherein the average number of pores per area of the bottom surface of the dissolvable sheet is from about 30 to about 35 pores/mm 2 .
  • Embodiment 132 The dissolvable sheet of any one of Embodiments 122-131, wherein the average number of pores per area of the bottom surface of the dissolvable sheet is about 34 pores/mm 2 .
  • Embodiment 133 The dissolvable sheet of any one of Embodiments 71-133, wherein the dissolvable sheet is shelf stable.
  • the phrases “at least one”, “one or more”, and “and/or” are open-ended expressions that are both conjunctive and disjunctive in operation.
  • each of the expressions “at least one of A, B and C”, “at least one of A, B, or C”, “one or more of A, B, and C”, “one or more of A, B, or C” and “A, B, and/or C” mean A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B and C together.
  • “or” may refer to “and”, “or,” or “and/or” and may be used both exclusively and inclusively.
  • the term “A or B” may refer to “A or B”, “A but not B”, “B but not A”, and “A and B”. In some cases, context may dictate a particular meaning.
  • the term “about” a number refers to that number plus or minus 10% of that number and/or within one standard deviation (plus or minus) from that number.
  • the term “about” a range refers to that range minus 10% of its lowest value and plus 10% of its greatest value and that range minus one standard deviation its lowest value and plus one standard deviation of its greatest value.
  • the terms “increased”, “increasing”, or “increase” are used herein to generally mean an increase by a statically significant amount relative to a reference level.
  • the terms “increased,” or “increase,” mean an increase of at least 10% as compared to a reference level, for example an increase of at least about 10%, at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90% or up to and including a 100% increase or any increase between 10-100% as compared to a reference level.
  • Other examples of “increase” include an increase of at least 2-fold, at least 5 fold, at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, at least 1000-fold or more as compared to a reference level.
  • “decreased”, “decreasing”, or “decrease” are used herein generally to mean a decrease in a value relative to a reference level.
  • “decreased” or “decrease” means a reduction by at least 10% as compared to a reference level, for example a decrease by at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90% or up to and including a 100% decrease (e.g., absent level or non-detectable level as compared to a reference level), or any decrease between 10-100% as compared to a reference level.
  • dissolving encompass disintegration of a composition (e.g., dissolvable matrix or dissolvable sheet) described herein.
  • dissolving refers to a state wherein at least 80%, 85%, 90%, 95%, 97%, or at least 99% of the composition disintegrates in liquid medium.
  • the dissolvable matrix has particle sizes (as measured by volume) no greater than 0.00001%, 0.0001%, 0.001%, 0.01%, or 0.1% of the original volume of the dissolvable matrix.
  • additional methods are used to describe dissolution including break timing (time required to observe fracturing of a dissolvable matrix as it rests on the surface of a liquid with no force applied other than from the liquid itself). In some instances, fracturing is observed with the naked eye (without an magnification aid).
  • phospholipid-containing matrices of the disclosure comprise phospholipids, such as lecithin-derived phospholipids, whereas “matrices lacking phospholipids” lack phospholipids, such as lecithin-derived phospholipids.
  • a percentage weight by weight (w/w) of a component can be the % weight of the component relative to the dry weight of a dissolvable matrix.
  • Example 1 Methods for manufacturing an illustrative dissolvable matrix
  • the method for making a dissolvable matrix of the present disclosure comprises: 1) mixing one or more active ingredients, two or more excipients, with one excipient comprising phospholipids, such as lecithin-derived phospholipids, and a solvent to produce a liquid mixture, 2) printing the liquid mixture, and 3) curing the mixture; thereby obtaining the dried dissolvable matrix suitable for storage or for use.
  • dry materials comprising a combination of active ingredients (e.g., vitamins/minerals, prebiotics, immune enhancers, sleep enhancers, and performance enhancers, as identified in the below Examples) and excipients (e.g., as identified in Table 1A as Matrix la, Matrix 1, Matrix 2, and Matrix 2a, and - in particular, phospholipids, such as lecithin-derived phospholipids) are blended into a premix and place into purified water at 60°C. Material was then mixed at variable RPMs for 15 min to achieve the proper rheology and viscosity range (5000-13000 cP) to form a liquid mixture for printing. After target viscosity was achieved, the liquid mixture was placed or pumped to the printer and stencil.
  • active ingredients e.g., vitamins/minerals, prebiotics, immune enhancers, sleep enhancers, and performance enhancers, as identified in the below Examples
  • excipients e.g., as identified in Table 1
  • each stencil an amount of the liquid mixture is added such that the unit dry weight (UDW) of a resulting dried dissolvable matrix, i.e., dissolvable sheet, was about 1.4 grams.
  • the stencil was set to a specific gauge of 14. Squeegee durometer, edge shape, and blade orientation also help determine the weight of deposition.
  • the material is cured in a convection oven set at a temperature from about 70°C to about 90°C until the resulting matrix contains less than 4% moisture.
  • Each dissolvable matrix i.e., dissolvable sheet, has a dry weight of approximately 1.4 grams.
  • An illustrative dissolvable matrix after curing is shown in FIG. 3A and FIG. 3B.
  • the resulting dissolvable matrices possess exceptional dissolution properties. In one illustrative dissolvable matrix (as described in Example 2), the matrix rapidly dissolves, without agitation, in about 15°C water in about 10 to about 20 seconds. See FIGS. 4A-4D.
  • a matrix dissolves in about 15°C water in about 10 to about 15 seconds. This rate of dissolution is surprisingly increased relative to a dissolvable matrix that lacks phospholipids, which typically dissolves under similar conditions in about 45 seconds to about 60 seconds.
  • a “phospholipid-containing matrix of the disclosure”, a “herein-disclosed dissolvable matrix”, a “dissolvable matrix of the present disclosure” and the like comprises phospholipids, such as lecithin-derived phospholipids, whereas a “matrix lacking phospholipids” lacks phospholipids, such as lecithin-derived phospholipids.
  • some illustrative phospholipid-containing matrices of the disclosure weigh about 1.4 grams; this is over twice the weight of matrices lacking phospholipids (as shown in FIG. 2A and FIG. 2B) Due, in part, to this increase in weight, an advantage of some illustrative phospholipid-containing matrices of the present disclosure is that more active ingredients, e.g., vitamins, prebiotics, immune enhancers, sleep enhancers, and performance enhancers, may be included in a dissolvable matrix and without reducing desirable properties of the disc, e.g., flexibility and rate of dissolution.
  • a phospholipid-containing matrix may include from about 25% to about 250% more active ingredients when compared to a matrix lacking phospholipids.
  • additional force may be applied when forming a disc. This further allows a larger z-axis and/or heavier disc, which permits a greater amount of active ingredients to be included in a phospholipid-containing matrix of the present disclosure.
  • the illustrative phospholipid-containing matrices of the present disclosure may have — on a bottom surface — pores that substantially lack j agged edges and/or interpore regions that substantially lack trabeculated structures. Compare the smooth pores and interpore regions shown in FIG. 3B of an illustrative phospholipid-containing matrix of the present disclosure with the jagged edges and trabeculated interpore regions for a matrix lacking phospholipids (as shown in FIG. 2B). Thus, the phospholipid-containing matrices of the present disclosure show signs of proper emulsification and homogeneity.
  • one excipient may be a lecithin or other composition comprising one or more phospholipids.
  • the lecithin included in the excipient fraction is sunflower lecithin. More preferably, the sunflower lecithin is de-oiled lecithin.
  • the sunflower lecithin is combined with avocado oil.
  • the avocado oil has relatively long fatty acid chain (e.g. from C12 to C18 in length) and protects DHA from oxidation from the free magnesium oxide remaining from the chelation reaction to form magnesium malate.
  • lecithin instead of merely acting as a strong emulsifier, lecithin also acted as a film-former.
  • lecithin in phospholipid-containing matrices allowed a reduction in the amounts of other film-formers, e.g., pullulan.
  • the inclusion of lecithin in a matrix shifted away from the dominant polysaccharide film structure into a more fluid-like film; this shift may contribute to smoothpore appearance (as shown in FIG. 3B, versus FIG. 2B) and to an increased flexibility of the phospholipid-containing matrices of the present disclosure.
  • the increased flexibility and/or the improved dissolution observed with phospholipid-containing matrices of the present disclosure may, in part, be due the presence lecithin in a mixture, which provided smaller pores and pores that substantially lack jagged edges and/or interpore regions that substantially lack trabeculated structures.
  • Example 2 Preparation of an illustrative dissolvable Matrix la comprising a multivitamin and mineral supplement
  • a dissolvable matrix comprising a multivitamin and mineral supplement was prepared.
  • Example 1 the general procedure of Example 1 was followed for a Matrix la formulation as disclosed in Table 1A and including phospholipids, such as lecithin-derived phospholipids, with active ingredients identified in the following table:
  • FIG. 3 A and FIG. 3B Images of an illustrative multivitamin and mineral supplementation dissolvable matrix are shown in FIG. 3 A and FIG. 3B.
  • FIG. 3C reproduces FIG. 3B (left) and FIG. 3C shows an ImageJ analysis of FIG. 3B and FIG. 2C reproduces FIG. 2B (left) and FIG. 2C shows an ImageJ analysis of FIG. 2B.
  • GIMP GNU Image Manipulation Program
  • ImageJ (a free image analysis software for microscopy applications) was used to quantify pore sizes.
  • the method comprised: 1) opening the GIMP image in the ImageJ software, 2) setting the image scale to a field of view with a radius of 2 mm, 3) duplicating the image, 4) setting the image to 8-bit grayscale type, 5) setting the color threshold to represent pores in original image, 6) touching up the image based on features in original image, 7) analyzing the particles by sorting based on minimum pore size (no max pore size is needed), and 8) logging the data.
  • the resulting dissolvable matrices possess exceptional dissolution.
  • the multivitamin and mineral supplementation phospholipid-containing matrix of the present disclosure rapidly dissolved, without agitation, in about 15°C water in about 10 to about 20 seconds. See FIG. 4A to FIG. 4D. This rate of dissolution is surprisingly increased relative to a dissolvable matrix that lacks phospholipids, which typically dissolves under similar conditions in about 45 seconds to about 60 seconds.
  • the top surface of the dissolvable matrix of this Example which is defined as the surface that is exposed to the air during dissolvable matrix formation, is distal to the stencil’s surface, (e.g., FIG. 3A), dissolved at the same rate as the bottom surface (e.g., FIG. 3B).
  • Example 3 Preparation of an illustrative dissolvable Matrix 3 comprising a multivitamin and mineral supplement
  • a dissolvable matrix comprising a multivitamin and mineral supplement was prepared.
  • Example 1 the general procedure of Example 1 was followed for a Matrix 3 formulation as disclosed in Table 1C and including phospholipids, such as lecithin-derived phospholipids, with active ingredients identified in the following table:
  • FIG. 5A top surface
  • FIG. 6A bottom surface
  • Images of an illustrative multivitamin and mineral supplement as a dissolvable matrix with low phospholipids (0.16% (w/w) phospholipids relative to the matrix) are shown in FIG. 5C (top surface) and FIG. 6C (bottom surface).
  • Images of an illustrative multivitamin and mineral supplement as a dissolvable matrix with high phospholipids (1.16% (w/w) phospholipids relative to the matrix) are shown in FIG. 5E (top surface) and FIG. 6E (bottom surface).
  • FIG. 5A The pore sizes of the top surface of the multivitamin and mineral supplementation dissolvable matrix (FIG. 5A) were compared to pore sizes of the top surface of a dissolvable matrix with low phospholipids (FIG. 5C) and pore sizes of the top surface of a dissolvable matrix with high phospholipids (FIG. 5E).
  • FIG. 6A The pore sizes of the bottom surface of the multivitamin and mineral supplementation dissolvable matrix (FIG. 6A) were compared to pore sizes of the bottom surface of a dissolvable matrix with low phospholipids (FIG. 6C) and pore sizes of the bottom surface of a dissolvable matrix with high phospholipids (FIG. 6E).
  • the SEM images were analyzed using a method analogous to the method described in example 2. From the Imaged logged data, the following metrics were obtained: 1) void volume (% of total focal area), 2) mean more size (mm 2 ), 3) the standard deviation of pore size (mm 2 ), 4) median pores area (mm 2 ), 5) pores per area (pores/mm 2 ), and 6) the distribution of pores. Each image was analyzed to create a pore distribution that was characterized by the mean, median, and standard deviation. Pores were counted based on adherence to actual features within the original image. The data was plotted as histograms and shown in FIGS.
  • FIG. 7A Images of the z-axis of an illustrative dissolvable matrix 3 are shown in FIG. 7A. Images of the z-axis of an illustrative multivitamin and mineral supplement as a dissolvable matrix with low phospholipids are shown in FIG. 7B. Images of the z-axis of an illustrative multivitamin and mineral supplement as a dissolvable matrix with high phospholipids are shown in FIG. 7C.
  • Imaged was used to quantify Z-axis length.
  • the method comprised: 1) opening the image in the Imaged software, 2) setting the image scale to a field of view with a radius of 2 mm, 3) measuring the length with the line tool, and 4) logging the data. From the logged data, the following metrices were obtained: 1) Z-axis length of the matrices (pm); and 2) the standard deviation of Z-axis length (pm).
  • the multivitamin and mineral supplementation dissolvable matrix 3 i.e., a phospholipid-containing matrix
  • the multivitamin and mineral supplement of dissolvable matrix 3 has higher z-axis length, i.e. is thicker, than the z-axis length of a dissolvable matrix with lower phospholipids or a higher phospholipids.
  • the matrix with low phospholipids showed an increased and unfavorable bulk density alongside decreased solubility and grainy ink that was unable to print evenly.
  • the matrix with high phospholipids keep the bulk density relatively increased but changed the overall graininess of the ink. Overall, matrix 3 provided the optimal composition for multivitamin and mineral supplements.
  • Example 4 Preparation of an illustrative dissolvable Matrix 1 for prebiotic supplement [0428] A dissolvable matrix for improving digestive health is prepared.
  • Example 1 The general procedure of Example 1 is followed with modification such that the active ingredients comprise comprising a bacteriophage component, blueberry powder, green tea extract, pomegranate powder, and acerola powder in some cases, acerola powder acts as both an active ingredient and as an excipient.
  • Example 5 Preparation of an illustrative dissolvable Matrix 1 comprising B vitamins [0430] A dissolvable matrix comprising B vitamins is prepared.
  • Example 1 The general procedure of Example 1 and Example 3 is followed, with modification such that the active ingredients comprise: riboflavin-5-phosphate, methylcobalamin, L- methyltetrahydrofolate (L-MTHF) calcium salt, pyridoxal-5-phosphate, and thiamine HC1.
  • active ingredients comprise: riboflavin-5-phosphate, methylcobalamin, L- methyltetrahydrofolate (L-MTHF) calcium salt, pyridoxal-5-phosphate, and thiamine HC1.
  • phospholipids such as lecithin-derived phospholipids
  • pullulan xylitol
  • powdered cellulose quillaja extract powder
  • refined glycerine microcrystalline cellulose
  • stevia extract (leaf) stevia rebaudiana
  • citric acid flavor
  • flavor and medium-chain triglyceride (MCT) oil powder
  • Example 6 Preparation of an illustrative dissolvable Matrix la for prebiotic supplement [0432] A dissolvable matrix for digestive health is prepared.
  • Example 1 The general procedure of Example 1 and Example 2 is followed, with modification such that the active ingredients comprise a mixture of a bacteriophage component, blueberry powder, green tea extract, pomegranate powder, and acerola powder; in some cases, acerola powder acts as both an active ingredient and as an excipient.
  • the excipients identified for Matrix la in Table 1A - in particular, phospholipids, such as lecithin-derived phospholipids - with or without the specific components pullulan, xylitol, and refined glycerin are used.
  • Example 7 Preparation of an illustrative dissolvable Matrix la for prebiotic supplement [0434] A dissolvable matrix for digestive health is prepared.
  • Example 5 The general procedure of Example 5 is followed, with modification, such that the excipients include quillaja extract powder, microcrystalline cellulose, stevia leaf, flavoring, and MCT oil powder.
  • the excipients include quillaja extract powder, microcrystalline cellulose, stevia leaf, flavoring, and MCT oil powder.
  • Example 8 Preparation of a illustrative dissolvable Matrix la for performance enhancement [0436] A dissolvable matrix for performance enhancement is prepared.
  • Example 1 For the first illustrative matrix, the general procedure of Example 1 and Example 6 is followed with modification such that the active ingredients comprise mango leaf extract, methylcobalamin, L-methyltetrahydrofolate Ca, pyridoxal-5-phosphate.
  • phospholipids such as lecithin-derived phospholipids — with or without the specific components pullulan, xylitol, powdered cellulose, quillaj a extract powder, refined glycerin, microcrystalline cellulose (MCC), stevia extract
  • Example 9 Preparation of an illustrative dissolvable Matrix 2 for sleep improvement [0438] A dissolvable matrix for sleep improvement is prepared.
  • Example 1 The general procedure of Example 1 was followed with modification such that the active ingredients comprise chamomile extract, L-theanine, and melatonin.
  • the excipients identified for Matrix 2 in Table 1A - in particular, phospholipids, such as a lecithin-derived phospholipids — with or without the specific components pullulan, xylitol, powdered cellulose, quillaj a extract powder, refined glycerin, oat fiber, stevia extract, citric acid, carboxymethyl cellulose (CMC) gum, flavoring, and coloring agent are used.
  • phospholipids such as a lecithin-derived phospholipids — with or without the specific components pullulan, xylitol, powdered cellulose, quillaj a extract powder, refined glycerin, oat fiber, stevia extract, citric acid, carboxymethyl cellulose (CMC) gum, flavoring, and coloring agent are used.
  • CMC carboxy
  • the flavoring is blueberry flavor and the coloring agent is a blue powder.
  • Example 10 Preparation of an illustrative dissolvable Matrix 2a for promoting immunity [0441] A dissolvable matrix for improving immunity is prepared.
  • Example 1 The general procedure of Example 1 was followed with modification such that the active ingredients comprise lecithinized-quercetin, vitamin D3 veg (vegetable) powder, ascorbic acid, and zinc picolinate.
  • the excipients identified for Matrix 2a in Table 1A - in particular, phospholipids, such as a lecithin-derived phospholipids - with or without the specific components pullulan, calcium carbonate, powdered cellulose, refined glycerin, tapioca starch, stevia extract, citric acid, quillaj a extract powder, and flavoring are used.
  • the flavoring is Meyer lemon flavor.

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Abstract

L'invention concerne des compositions solubles. L'invention concerne en outre des compositions solubles comprenant des phospholipides et des principes actifs. L'invention concerne en outre des procédés d'impression de compositions solubles.
PCT/US2023/064163 2022-03-10 2023-03-10 Disques contenant des phospholipides et procédés de fabrication WO2023173104A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1621080A1 (fr) * 2004-07-30 2006-02-01 Wm. Wrigley Jr. Company Compositions de films comestibles
WO2010151020A2 (fr) * 2009-06-25 2010-12-29 (주) 벡스코아 Film oral à dissolution rapide pour masquer efficacement les goûts désagréables
WO2022055985A1 (fr) * 2020-09-08 2022-03-17 Nutrativa Llc Matrices solubles
US20220296567A1 (en) * 2014-07-28 2022-09-22 Concept Matrix Solutions Oral dissolvable film that includes plant extract

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1621080A1 (fr) * 2004-07-30 2006-02-01 Wm. Wrigley Jr. Company Compositions de films comestibles
WO2010151020A2 (fr) * 2009-06-25 2010-12-29 (주) 벡스코아 Film oral à dissolution rapide pour masquer efficacement les goûts désagréables
US20220296567A1 (en) * 2014-07-28 2022-09-22 Concept Matrix Solutions Oral dissolvable film that includes plant extract
WO2022055985A1 (fr) * 2020-09-08 2022-03-17 Nutrativa Llc Matrices solubles

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