WO2023173111A2 - Intra-dosage form coatings and applications thereof - Google Patents

Intra-dosage form coatings and applications thereof Download PDF

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Publication number
WO2023173111A2
WO2023173111A2 PCT/US2023/064173 US2023064173W WO2023173111A2 WO 2023173111 A2 WO2023173111 A2 WO 2023173111A2 US 2023064173 W US2023064173 W US 2023064173W WO 2023173111 A2 WO2023173111 A2 WO 2023173111A2
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WO
WIPO (PCT)
Prior art keywords
mass
coating formulation
dosage form
choline
active ingredient
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2023/064173
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English (en)
French (fr)
Other versions
WO2023173111A3 (en
Inventor
Clayton Ericson
Ren A. Gonzalez
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Balchem Corp
Original Assignee
Balchem Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Balchem Corp filed Critical Balchem Corp
Priority to CN202380024059.1A priority Critical patent/CN118946346A/zh
Priority to US18/845,997 priority patent/US20250073175A1/en
Priority to JP2024548573A priority patent/JP2025506698A/ja
Priority to KR1020247027473A priority patent/KR20250023329A/ko
Priority to EP23767759.6A priority patent/EP4489731A4/en
Publication of WO2023173111A2 publication Critical patent/WO2023173111A2/en
Publication of WO2023173111A3 publication Critical patent/WO2023173111A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars

Definitions

  • the present disclosure relates to coating formulations and methods of use and making thereof. Accordingly, the present disclosure relates to the fields of chemistry, pharmacy, and dietary supplementation.
  • Choline is an essential nutrient that is present in many foods. Although choline is available in dietary supplements, it is rarely included in dosage forms such as multivitamins that include vitamin C. This is generally due to the hygroscopic nature of choline. When vitamin C degrades, it creates black spots on the surface of the dosage form that makes it unappealing to consumers. Furthermore, this also reduces the potency of vitamin C in the dosage form, forcing manufacturers to either overformulate the dosage form or risk failing the label claim of vitamin C.
  • the choline absorbs moisture from the air or from other components in the dosage form, accelerating the degradation of vitamin C. Additionally, the presence of metals and metal oxides in the dosage form accelerates the degradation of vitamin C. Moreover, other agents in the dosage form can also accelerate spotting, such as magnesium oxide, ferrous fumarate, and dicalcium phosphate. This accelerates the spotting caused by vitamin C degradation.
  • coating formulations comprising shellac that, when coated on at least one active ingredient in a multi-ingredient dosage form, prevent spotting in the dosage form.
  • the at least one active ingredient has a concentration of between about 50.0 mass % to about 95.0 mass % relative to the total mass of the at least one active ingredient and the coating formulation.
  • the at least one active ingredient comprises vitamin C.
  • the vitamin C is selected from the group consisting of ascorbic acid, ferrous ascorbate, magnesium ascorbate, sodium ascorbate, calcium ascorbate, zinc ascorbate, molybdenum ascorbate, chromium ascorbate, manganese ascorbate, lithium ascorbate, potassium ascorbate, nickel ascorbate, silver ascorbate, and any combination thereof.
  • the vitamin C is present in an amount of between about 50 mass % to about 95 mass % relative to the combined mass of the vitamin C and the coating formulation.
  • the at least one active ingredient comprises choline.
  • the choline is selected from the group consisting of choline chloride, choline bitartrate, phosphatidyl choline, choline dihydrogen citrate, alpha glycerylphosphorylcholine, cytidine diphosphate-choline, choline folate, an ester of choline with DHA, esters of choline with 3-methyl-2-hexenoic acid (MHA), esters of choline with medium chain triglycerides, other esters of choline with fatty acids, other salts of choline, or combinations thereof.
  • the choline is present in an amount of between about 50 mass % to about 95 mass % relative to the combined mass of the choline and the coating formulation.
  • the shellac has a concentration of between about 1 mass % to about 50 mass % relative to the combined mass of the at least one active ingredient and the coating formulation.
  • the coating formulation coating formulation further comprises at least one of hydroxypropylcellulose, silicon dioxide, starch, microcrystalline cellulose, ethylcellulose, talc, and combinations thereof.
  • the coating formulation further comprises a silicate.
  • the silicate includes silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or combinations thereof.
  • the silicate includes silicon dioxide, and the silicon dioxide is present in the coating formulation in an amount of about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the silicon dioxide is at least one of colloidal silicon dioxide or fumed silica.
  • the coating formulation includes cellulose or a derivative thereof.
  • the cellulose or a derivative thereof includes microcrystalline cellulose, powdered cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hypromellose, carboxymethylcellulose, or combinations thereof.
  • the coating formulation further comprises hydroxypropylcellulose.
  • the hydroxypropylcellulose is present in the coating formulation in an amount of about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the coating formulation further comprises microcrystalline cellulose.
  • the microcrystalline cellulose is present in the coating formulation in an amount of about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the first active ingredient and second active ingredient.
  • the coating formulation further comprises ethylcellulose.
  • the ethylcellulose is present in the coating formulation in an amount of about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the first active ingredient or the second active ingredient.
  • the coating formulation further comprises starch.
  • the starch includes maize starch, potato starch, rice starch, wheat starch, tapioca starch, or combinations thereof.
  • the starch is present in the coating formulation in an amount of about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the first active ingredient or the second active ingredient.
  • a multi-ingredient dosage form comprising at least one active ingredient and a coating formulation comprising shellac, wherein the coating formulation coats the at least one active ingredient.
  • the shellac is present in an amount between about 1 mass % to about 50 mass % relative to the total mass of the at least one active ingredient and the coating formulation.
  • the at least one active ingredient has a concentration of between about 50.0 mass % to about 95.0 mass % relative to the combined mass of the at least one active ingredient and the coating formulation.
  • the at least one active ingredient comprises vitamin C.
  • the vitamin C is selected from the group consisting of ascorbic acid, ferrous ascorbate, magnesium ascorbate, sodium ascorbate, calcium ascorbate, zinc ascorbate, molybdenum ascorbate, chromium ascorbate, manganese ascorbate, lithium ascorbate, potassium ascorbate, nickel ascorbate, silver ascorbate, and any combination thereof.
  • the vitamin C is present in the dosage form in an amount of about 1 mg to about 2000 mg.
  • the at least one active ingredient comprises choline.
  • the choline is selected from the group consisting of choline chloride, choline bitartrate, phosphatidyl choline, choline dihydrogen citrate, alpha glycerylphosphorylcholine, cytidine diphosphate-choline, choline folate, an ester of choline with DHA, esters of choline with 3-methyl-2-hexenoic acid (MHA), esters of choline with medium chain triglycerides, other esters of choline with fatty acids, other salts of choline, or combinations thereof.
  • the choline is present in the dosage form in an amount of about 1 mg to about 2000 mg.
  • the coating formulation further comprises a silicate, a starch, cellulose or a derivative thereof, or a combination thereof.
  • the at least one active ingredient comprises vitamin C and choline, and both the vitamin C and the choline are coated by the coating formulation.
  • the at least one active ingredient comprises choline and the dosage form further comprises vitamin C, and the vitamin C is not coated by the coating formulation.
  • the at least one active ingredient comprises vitamin C and the dosage form further comprises choline, wherein the choline is not coated by the coating formulation.
  • the multi-ingredient dosage form is a tablet, capsule, gummy, beverage, bar, suspension, granulation, powder, lozenge, troche, granule, pill, gel cap.
  • the dosage form further comprises at least one of vitamins, minerals, supplements, and excipients.
  • the multi-ingredient dosage form wherein the multi-ingredient dosage form shows little spotting after storage for about 18 days, 30 days, or 60 days at 25°C and 20% relative humidity. In some embodiments, the multi-ingredient dosage form, wherein the multi-ingredient dosage form shows little spotting after storage for about 18 days, 30 days, or 60 days at 25°C and 30% relative humidity. In some embodiments, the multi-ingredient dosage form, wherein the multi-ingredient dosage form shows little spotting after storage for about 18 days, 30 days, or 60 days at 45°C and 20% relative humidity. In some embodiments, the multi-ingredient dosage form, wherein the multi-ingredient dosage form shows little spotting after storage for about 18 days, 30 days, or 60 days at 45°C and 30% relative humidity.
  • the method includes providing an active ingredient comprising at least one of vitamin C and choline; coating the active ingredient in a coating formulation comprising shellac; and including the active ingredient coated in the coating formulation in a dosage form.
  • FIG. 1 shows spotting for the tablet of Example 1 containing vitamin C but no choline under different storage conditions.
  • FIGS. 2A-2D show four different commercially available tablets stored under different conditions.
  • FIG. 3 shows spotting for the tablet of Example 1 containing choline and vitamin C under different storage conditions for 18 days. The temperature ranged from 25°C to 85°C and relative humidity ranged from 0% RH to 60% RH.
  • FIG. 4 shows spotting for the tablet of Example 1 containing choline and vitamin C under refrigerated storage conditions (4°C) at 0% RH, 30% RH, and 60% RH, for 18 days.
  • FIGS. 5A and 5B show spotting under different storage conditions for the tablet of Example 1 containing various forms of choline and vitamin C.
  • FIGS. 6A and 6B show spotting under different storage conditions for the tablet of Example 1 containing various dosage forms, different forms of vitamin C, and choline.
  • FIG. 7 shows spotting under different storage conditions for the tablet of Example 1 including vitamin C, choline, and a coating formulation of the present disclosure comprising talc.
  • FIG. 8 shows progression of spotting under different storage conditions for the tablet of Example 1 , including vitamin C, choline, and a coating formulation of the present disclosure comprising talc.
  • FIG. 9 shows the progression of spotting for tablets under different storage conditions, wherein the tablets contain vitamin C, choline, and a coating formulation of the present disclosure consisting of shellac.
  • FIG. 10 shows the progression of spotting for tablets of Example 1 under different storage conditions, wherein the tablets contain vitamin C, choline, and either a coating formulation of the present disclosure consisting of shellac or no coating formulation.
  • FIG. 11 shows the progression of spotting for tablets of Example 1 under different storage conditions, wherein the tablets contain a coating formulation of the present disclosure coated on choline, on vitamin C, or on both.
  • FIGS. 12A-12G show colorimeter diagrams for various tablets having various coating formulations of the present disclosure.
  • FIG. 13 shows the tablets and the AE values for various tablets containing various coating formulations of the present disclosure.
  • FIGS. 14A-14B show colorimeter diagrams for various tablets that do not contain a coating formulation of the present disclosure.
  • FIG. 14C shows exemplary samples used in the colorimeter experiments.
  • the term “about” is used to provide flexibility to a numerical range endpoint by providing that a given value may be “a little above” or “a little below” the endpoint.
  • the endpoint may be within 10%, 8%, 5%, 3%, 2%, or 1 % of the listed value.
  • a numerical range of “about 50 mg/mL to about 80 mg/mL” should also be understood to provide support for the range of “50 mg/mL to 80 mg/mL”
  • the endpoint may also be based on the variability allowed by an appropriate regulatory body, such as the FDA, USP, etc.
  • spotting refers to the formation of black spots on a dosage form that contains vitamin C and, optionally, choline chloride.
  • the term “choline” refers to both the N,N,N- trimethylethanolammonium cation as well as the various quarternary ammonium salts, phospholipid-bound forms of the cation, esters of the cation with fatty acids or medium chain triglycerides, and other molecules containing the cation.
  • the term “choline” may be used interchangeably with “choline salt”, “phospholipid-bound forms of choline”, “esters of choline with fatty acids”, etc.
  • choline salt refers specifically to a salt form of the N,N,N-trimethylethanolammounium cation
  • esters of choline with medium chain triglycerides it refers specifically to an esterified form of the N,N,N-trimethylethanolammonium cation; and so on.
  • vitamin C refers to both the ascorbate ion having the molecular formula CeHyOe ⁇ as well as the acid, salt, and oxidized forms of the ascorbate ion.
  • vitamin C may be used interchangeably with “ascorbic acid”.
  • amounts or concentrations of vitamin C are referred to herein, they generally refer to the concentration or the amount of the ascorbate ion; for example, the phrase “the vitamin C may be present in the amount of 1 mg” generally means herein that the amount of the ascorbate ion is 1 mg.
  • shellac refers to the resin secreted by the female lac bug.
  • the term encompasses raw shellac, liquid shellac, and shellac that has been processed, modified, or purified through methods known to those having skill in the art, particularly through methods known for preparing shellac for pharmaceutical use.
  • the term includes derivatives or analogues of shellac.
  • coating formulations that are useful in preventing spotting in multi-ingredient dosage forms containing vitamin C and, optionally, choline chloride.
  • the coating formulations comprise shellac.
  • the coating formulations may reduce the rate of degradation of vitamin C by protecting the vitamin C from moisture and reducing contact with other ingredients (e.g., metals and metal oxides) within the multi-ingredient dosage form.
  • the coating formulations may prevent choline chloride from absorbing excess moisture from the environment or from other components in the dosage form, which may accelerate the degradation of vitamin C.
  • the coating formulation is resistant to fracturing when compressed, allowing the coating formulation to be used in tablets and other dosage forms manufactured by compression.
  • the coating formulation includes shellac.
  • the coating formulation may consist of or consist essentially of shellac.
  • the coating formulation surrounds an active ingredient.
  • the coating formulation may completely surround the active ingredient or may substantially surround the active ingredient (i.e. , 95% or more of the active ingredient).
  • the coating formulation does not coat the entire dosage form and only coats the active ingredients described below.
  • the particle size of the coated active ingredient may be from about 1 micron to about 2000 microns.
  • the particle size of the coated active ingredient may be from about 1 micron to about 50 microns, about 50 microns to about 100 microns, about 100 microns to about 250 microns, about 250 microns to about 500 microns, about 500 microns to about 750 microns, about 750 microns to about 1000 microns, about 1000 microns to about 1250 microns, about 1250 microns to about 1500 microns, about 1500 microns to about 1750 microns, or about 1750 microns to about 2000 microns.
  • the particle size of the coated active ingredient may be from about 1 micron to about 100 microns, about 1 micron to about 250 microns, about 1 micron to about 500 microns, about 1 micron to about 750 microns, about 1 micron to about 1000 microns, about 1 micron to about 1250 microns, about 1 micron to about 1500 microns, about 1 micron to about 1750 microns, about 50 microns to about 2000 microns, about 100 microns to about 2000 microns, about 250 microns to about 2000 microns, about 500 microns to about 2000 microns, about 750 microns to about 2000 microns, about 1000 microns to about 2000 microns, about 1250 microns to about 2000 microns, or about 1500 microns to about 2000 microns.
  • the particle size of the coated active ingredient may be about 1 micron, 50 microns, 100 microns, 200 microns, 300 microns, 400 microns, 500 microns, 600 microns, 700 microns, 800 microns, 900 microns, 1000 microns, 1100 microns, 1200 microns, 1300 microns, 1400 microns, 1500 microns, 1600 microns, 1700 microns, 1800 microns, 1900 microns, or about 2000 microns.
  • the coating formulation may be present in an amount from about 5 mass % to about 50 mass % relative to the combined mass of the at least one active ingredient and the coating formulation. In some aspects, the coating formulation may be present in an amount from about 5 mass % to about 10 mass %, about 5 mass % to about 15 mass %, about 5 mass % to about 20 mass %, about 5 mass % to about 25 mass %, about 5 mass % to about 30 mass %, about 5 mass % to about 35 mass %, about 5 mass % to about 40 mass %, about 5 mass % to about 45 mass %, about 45 mass % to about 50 mass %, about 40 mass % to about 50 mass %, about 35 mass % to about 50 mass %, about 30 mass % to about 50 mass %, about 25 mass % to about 50 mass %, about 2 mass % to about 50 mass %, about 15 mass % to about 50 mass %, or about 10 mass % to about 50 mass % relative to the combined mass of the
  • the coating formulation may be present in an amount of about 5 mass %, 7.5 mass %, 10 mass %, 12.5 mass %, 15 mass %, 17.5 mass %, 20 mass %, 22.5 mass %, 25 mass %, 27.5 mass %, 30 mass %, 32.5 mass %, 35 mass %, 37.5 mass %, 40 mass %, 42.5 mass %, 45 mass %, 47.5 mass %, or about 50 mass % relative to the combined mass of the at least one active ingredient and the coating formulation.
  • the shellac may be present in the coating formulation in an amount from about 1 mass % to about 50 mass % relative to the combined mass of the at least one active ingredient and the coating formulation. In some aspects, the shellac may be present in an amount from about 1 mass% to about 5 mass %, about 1 mass % to about 10 mass %, about 1 mass % to about 15 mass %, about 1 mass % to about 20 mass %, about 1 mass % to about 25 mass %, about 1 mass % to about 30 mass %, about 1 mass % to about 35 mass %, about 1 mass % to about 40 mass %, about 1 mass % to about 45 mass %, about 45 mass % to about 50 mass %, about 40 mass % to about 50 mass %, about 35 mass % to about 50 mass %, about 30 mass % to about 50 mass %, about 25 mass % to about 50 mass %, about 2 mass % to about 50 mass %, about 15 mass % to about 50 mass %, about 10
  • the shellac may be present in an amount from about 1 mass %, 2.5 mass %, 5 mass %, 7.5 mass %, 10 mass %, 12.5 mass %, 15 mass %, 17.5 mass %, 20 mass %, 22.5 mass %, 25 mass %, 27.5 mass %, 30 mass %, 32.5 mass %, 35 mass %, 37.5 mass %, 40 mass %, 42.5 mass %, 45 mass %, 47.5 mass %, or about 50 mass % relative to the combined mass of the at least one active ingredient and the coating formulation. In some examples, the shellac may be present in an amount from about 5 mass % to about 20 mass % relative to the combined mass of the at least one active ingredient and the coating formulation.
  • the coating formulation may include a silicate, such as silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, and other silicates known in the art or combinations thereof.
  • the silicate acts as an adsorbent, an anti-caking agent, a glidant, a disintegrant, etc.
  • the silicon dioxide may include colloidal silicon dioxide, fumed (pyrogenated) silica, or other forms of silicon dioxide.
  • the silicate may be present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the silicate may be present in the coating formulation in an amount from about 0 mass % to about 2 mass %, 0 mass % to about 3 mass %, about 0 mass % to about 4 mass %, about 0 mass % to about 5 mass %, about 0 mass % to about 6 mass %, about 0 mass % to about 7 mass %, 0 mass % to about 8 mass %, about 0 mass % to about 9 mass %, about 1 mass % to about 10 mass %, about 2 mass % to about 10 mass %, about 3 mass % to about 10 mass %, about 4 mass % to about 10 mass %, about 5 mass % to about 10 mass %, about 6 mass % to about 10 mass %, about 7 mass % to about 10 mass %, about 8 mass % to about 10 mass %, about 0.5 mass % to about 5 mass %, or about 1 mass % to about 3 mass % relative to the combined mass of the coating formulation and the at least one
  • the silicate may be present in the coating formulation in an amount from about 0 mass % to about 1 mass %, about 1 mass % to about 2 mass %, about 2 mass % to about 3 mass %, about 3 mass % to about 4 mass %, about 4 mass % to about 5 mass %, about 5 mass % to about 6 mass %, about 6 mass % to about 7 mass %, about 7 mass % to about 8 mass %, about 8 mass % to about 9 mass %, or about 9 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the silicate may be present in the coating formulation in an amount of about 0.5 mass %, 1 mass %, 1.5 mass %, 2 mass %, 2.5 mass %, 3 mass %, about 4 mass %, about 5 mass %, about 6 mass %, about 7 mass %, about 8 mass %, about 9 mass %, or about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the silicate is present in the coating formulation in an amount from about 0.5 mass % to about 3 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the silicate is colloidal silicon dioxide.
  • the coating formulation may include starch, such as maize starch, potato starch, rice starch, wheat starch, tapioca starch, and other starches or combinations thereof.
  • starch acts as a lubricant and a low-solubility coating.
  • the starch may be present in the coating formulation in an amount from about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the starch may be present in the coating formulation in an amount from about 0 mass % to about 5 mass %, about 5 mass % to about 10 mass %, about 10 mass % to about 15 mass %, about 15 mass % to about 20 mass %, or about 20 mass % to about 25 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the starch may be present in the coating formulation in an amount from about 0 mass % to about 10 mass %, about 0 mass % to about 15 mass %, about 0 mass % to about 20 mass %, about 5 mass % to about 25 mass %, about 10 mass % to about 25 mass %, about 15 mass % to about 25 mass %, or about 5 mass % to about 20 mass %.
  • the starch may be present in the coating formulation in an amount of about 0 mass %, 1 mass %, 2 mass %, 3 mass %, 4 mass %, 5 mass %, 6 mass %, 7 mass %, 8 mass %, 9 mass %, 10 mass %, 11 mass %, 12 mass %, 13 mass %, 14 mass %, 15 mass %, 16 mass %, 17 mass %, 18 mass %, 19 mass %, 20 mass %, 21 mass %, 22 mass %, 23 mass %, 24 mass %, or about 25 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the starch is present in the coating formulation in an amount from about 9 mass % to about 16 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the coating formulation may include cellulose or derivatives thereof, such as microcrystalline cellulose, powdered cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hypromellose (e.g., hypromellose acetate succinate), carboxymethylcellulose (e.g., sodium carboxymethylcellulose), and combinations thereof.
  • the cellulose may be blended with other ingredients, such as carrageenan, phosphate salts (e.g., calcium phosphate), gums, (e.g., guar gum), mannitol, silicates, etc.
  • the coating formulation may include microcrystalline cellulose.
  • Microcrystalline cellulose acts as an adsorbent, compression aide, diluent, binder, and a disintegrant in the dosage forms described herein.
  • the microcrystalline cellulose may be present in the coating formulation in an amount from about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the microcrystalline cellulose may be present in an amount from about 0 mass % to about 5 mass %, about
  • the microcrystalline cellulose may be present in the coating formulation in an amount from about 0 mass % to about 10 mass %, about 0 mass % to about 15 mass %, about 0 mass % to about 20 mass %, about 5 mass % to about 25 mass %, about 10 mass % to about 25 mass %, about 15 mass % to about 25 mass %, or about 5 mass % to about 20 mass %.
  • the microcrystalline cellulose may be present in an amount of about 0 mass %, 1 mass %, 2 mass %, 3 mass %, 4 mass %, 5 mass %,
  • the microcrystalline cellulose is present in an amount of about 9 mass % to about 12 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the coating formulation may include hydroxypropylcellulose. Hydroxypropylcellulose adds flexibility to the coating.
  • the hydroxypropylcellulose may be present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the hydroxypropylcellulose may be present in the coating formulation in an amount from about 0 mass % to about 2 mass %, 0 mass % to about 3 mass %, about 0 mass % to about 4 mass %, about 0 mass % to about 5 mass %, about 0 mass % to about 6 mass %, about 0 mass % to about 7 mass %, 0 mass % to about 8 mass %, about 0 mass % to about 9 mass %, about 1 mass % to about 10 mass %, about 2 mass % to about 10 mass %, about 3 mass % to about 10 mass %, about 4 mass % to about 10 mass %, about 5 mass % to about 10 mass %, about 6 mass % to about 10 mass %, about 7 mass % to about 10 mass %, about 8 mass % to about 10 mass %, about 0.5 mass % to about 5 mass %, or about 1 mass % to about 3 mass % relative to the combined mass of the coating formulation and
  • the hydroxypropylcellulose may be present in the coating formulation in an amount from about 0 mass % to about 1 mass %, about 1 mass % to about 2 mass %, about 2 mass % to about 3 mass %, about 3 mass % to about 4 mass %, about 4 mass % to about 5 mass %, about 5 mass % to about 6 mass %, about 6 mass % to about 7 mass %, about 7 mass % to about 8 mass %, about 8 mass % to about 9 mass %, or about 9 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the hydroxypropylcellulose may be present in the coating formulation in an amount of about 0.5 mass %, 1 mass %, 1 .5 mass %, 2 mass %, 2.5 mass %, 3 mass %, about 4 mass %, about 5 mass %, about 6 mass %, about 7 mass %, about 8 mass %, about 9 mass %, or about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the hydroxypropylcellulose is present in the coating formulation in an amount from about 0.25 mass % to about 1.5 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the coating formulation may include hydroxypropylmethylcellulose. Hydroxypropylmethylcellulose adds flexibility to the coating.
  • the hydroxypropylmethylcellulose may be present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the hydroxypropylmethylcellulose may be present in the coating formulation in an amount from about 0 mass % to about 2 mass %, 0 mass % to about 3 mass %, about 0 mass % to about 4 mass %, about 0 mass % to about 5 mass %, about 0 mass % to about 6 mass %, about 0 mass % to about 7 mass %, 0 mass % to about 8 mass %, about 0 mass % to about 9 mass %, about 1 mass % to about 10 mass %, about 2 mass % to about 10 mass %, about 3 mass % to about 10 mass %, about 4 mass % to about 10 mass %, about 5 mass % to about 10 mass %, about 6 mass % to about 10 mass %, about 7 mass % to about 10 mass %, about 8 mass % to about 10 mass %, about 0.5 mass % to about 5 mass %, or about 1 mass % to about 3 mass % relative to the combined mass of the coating formulation
  • the hydroxypropylmethylcellulose may be present in the coating formulation in an amount from about 0 mass % to about 1 mass %, about 1 mass % to about 2 mass %, about 2 mass % to about 3 mass %, about 3 mass % to about 4 mass %, about 4 mass % to about 5 mass %, about 5 mass % to about 6 mass %, about 6 mass % to about 7 mass %, about 7 mass % to about 8 mass %, about 8 mass % to about 9 mass %, or about 9 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the hydroxypropylmethylcellulose may be present in the coating formulation in an amount of about 0.5 mass %, 1 mass %, 1.5 mass %, 2 mass %, 2.5 mass %, 3 mass %, about 4 mass %, about 5 mass %, about 6 mass %, about 7 mass %, about 8 mass %, about 9 mass %, or about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the coating formulation may further comprise ethylcellulose.
  • the ethylcellulose may be present in the coating formulation in an amount of from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the ethylcellulose may be present in the coating formulation in an amount from about 0 mass % to about 2 mass %, 0 mass % to about 3 mass %, about 0 mass % to about 4 mass %, about 0 mass % to about 5 mass %, about 0 mass % to about 6 mass %, about 0 mass % to about 7 mass %, 0 mass % to about 8 mass %, about 0 mass % to about 9 mass %, about 1 mass % to about 10 mass %, about 2 mass % to about 10 mass %, about 3 mass % to about 10 mass %, about 4 mass % to about 10 mass %, about 5 mass % to about 10 mass %, about 6 mass % to about 10 mass %, about 7 mass % to about 10 mass %, about 8 mass % to about 10 mass %, about 0.5 mass % to about 5 mass %, or about 1 mass % to about 3 mass % relative to the combined mass of the coating formulation and
  • the ethylcellulose may be present in the coating formulation in an amount from about 0 mass % to about 1 mass %, about 1 mass % to about 2 mass %, about 2 mass % to about 3 mass %, about 3 mass % to about 4 mass %, about 4 mass % to about 5 mass %, about 5 mass % to about 6 mass %, about 6 mass % to about 7 mass %, about 7 mass % to about 8 mass %, about 8 mass % to about 9 mass %, or about 9 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the ethylcellulose may be present in the coating formulation in an amount of about 0.5 mass %, 1 mass %, 1.5 mass %, 2 mass %, 2.5 mass %, 3 mass %, about 4 mass %, about 5 mass %, about 6 mass %, about 7 mass %, about 8 mass %, about 9 mass %, or about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the ethylcellulose is present in the coating formulation in an amount from about 0.1 mass % to about 1 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • the coating formulation may further comprise one or more excipients.
  • the one or more excipients may include sugar (e.g., lactose, dextrin, maltodextrin, glucose, sucrose, fructose, maltose, galactose, etc.), sugar alcohols (e.g., sorbitol, mannitol, xylitol, lactitol, isomalt, maltitol, erythritol, hydrogenated starch hydrolysates, etc.), other silicates (e.g., calcium silicate, magnesium silicate, and other forms of silicon dioxide), other derivatives of starch, other derivatives of cellulose (e.g., cellulose acetate, cellulose phthalate, etc.), alginates, stearates or stearic acid, dyes, colorants, flavoring agents, lubricants, binders, fillers, glidants, diluents, adsorbent
  • the coating formulation coats at least one active ingredient contained within a multi-ingredient dosage form.
  • the at least one active ingredient may include vitamin C and choline.
  • the at least one active ingredient may include vitamin C only, choline only, or both vitamin C and choline.
  • the multi-ingredient dosage form may contain both vitamin C and choline, but only one of the active ingredients is coated with the coating formulation of the present disclosure.
  • the multi-ingredient dosage form may contain both vitamin C and choline, which are both coated with the coating formulation of the present disclosure, but the composition of the coating formulation for the vitamin C differs from the composition of the coating formulation for the choline.
  • the multi-ingredient dosage form may contain both vitamin C and choline, which are both coated with a coating formulation of an identical composition.
  • the at least one active ingredient may include fat-soluble vitamins or their derivatives, such as vitamin A, vitamin D, vitamin E, vitamin K, and other fat-soluble vitamins known in the art and derivatives thereof.
  • the at least one active ingredient may include water-soluble vitamins or their derivatives, such as folate, thiamine, riboflavin, niacin, biotin, pantothenic acid, pyridoxine, cobalamin, and other water-soluble vitamins known in the art and derivatives thereof.
  • water-soluble vitamins or their derivatives such as folate, thiamine, riboflavin, niacin, biotin, pantothenic acid, pyridoxine, cobalamin, and other water-soluble vitamins known in the art and derivatives thereof.
  • the at least one active agent may include nutritionally relevant metals, such as sodium, potassium, calcium, magnesium, iron, copper, zinc, manganese, cobalt, chromium, and other nutritionally relevant metals known in the art and salts, complexes, or chelates thereof.
  • nutritionally relevant metals such as sodium, potassium, calcium, magnesium, iron, copper, zinc, manganese, cobalt, chromium, and other nutritionally relevant metals known in the art and salts, complexes, or chelates thereof.
  • the at least one active ingredient may include a drug or pharmaceutical agent, such an analgesic agent, an anti-inflammatory agent, an anti- arrhythmic agent, an anti-asthma agent, an anti-bacterial agent, an anti-viral agent, an anti-coagulant, an anti-depressant, an anti-diabetic, an anti-epileptic, an anti-fungal agent, an anti-hypertensive agent, an anti-malarial, an anti-migraine agent, an anti- muscarinic agent, an anti-neoplastic agent, an immunosuppressant, an anti-protozoal agent, an anti-thyroid agent, an anxiolytic agent, a sedative, a hypnotic agent, a neuroleptic agent, a beta-Blocker, a cardiac inotropic agent, a corticosteroid, a diuretic agent, an anti-Parkinsonian agent, a gastrointestinal agent, an anti-histamine, a histamine
  • the at least one active ingredient may include vitamin C.
  • the vitamin C may include ascorbic acid, ferrous ascorbate, magnesium ascorbate, sodium ascorbate, calcium ascorbate, zinc ascorbate, molybdenum ascorbate, chromium ascorbate, manganese ascorbate, lithium ascorbate, potassium ascorbate, nickel ascorbate, silver ascorbate, or any other forms of vitamin C known in the art or combinations thereof.
  • the vitamin C is ascorbic acid.
  • the vitamin C may be present in an amount of between about 50 mass % to about 95 mass % relative to the combined mass of the vitamin C and the coating formulation. In some aspects, the vitamin C may be present in an amount from about 50 mass % to about 55 mass %, about 55 mass % to about 60 mass %, about 60 mass % to about 65 mass %, about 65 mass % to about 70 mass %, about 70 mass % to about 75 mass %, about 75 mass % to about 80 mass %, about 80 mass % to about 85 mass %, about 85 mass % to about 90 mass %, or about 90 mass % to about 95 mass % relative to the combined mass of the vitamin C and the coating formulation.
  • the vitamin C may be present in an amount from about 50 mass % to about 60 mass %, about 50 mass % to about 65 mass %, about 50 mass % to about 70 mass %, about 50 mass % to about 75 mass %, about 50 mass % to about 80 mass %, about 50 mass % to about 85 mass %, about 50 mass % to about 90 mass %, about 55 mass % to about 95 mass %, about 60 mass % to about 95 mass %, about 65 mass % to about 95 mass %, about 70 mass % to about 95 mass %, about 75 mass % to about 95 mass %, about 80 mass % to about 95 mass %, or about 85 mass % to about 95 mass % relative to the combined weight of the vitamin C and the coating formulation.
  • the vitamin C may be present in an amount of about 50 mass %, 55 mass %, 60 mass %, 65 mass %, 70 mass %, 75 mass %, 80 mass %, 85 mass %, 90 mass %, or about 95 mass % relative to the combined mass of the vitamin C and the coating formulation. In some exemplary embodiments, the vitamin C may be present in an amount from about 70 mass % to about 80 mass % relative to the combined mass of the vitamin C and the coating formulation. ii. Choline
  • the at least one active ingredient may include choline.
  • the choline may include choline chloride, choline bitartrate, phosphatidyl choline, choline dihydrogen citrate, alpha glycerylphosphorylcholine, cytidine diphosphatecholine, choline folate, an ester of choline with DHA, esters of choline with 3-methyl-2- hexenoic acid (MHA), esters of choline with medium chain triglycerides, other esters of choline with fatty acids, other salts of choline, or combinations thereof.
  • the choline is choline bitartrate.
  • the choline may be present in an amount from about 50 mass % to about 95 mass % relative to the combined weight of the coating formulation and the choline. In some aspects, the choline may be present in an amount from about 50 mass % to about 55 mass %, about 55 mass % to about 60 mass %, about 60 mass % to about 65 mass %, about 65 mass % to about 70 mass %, about 70 mass % to about 75 mass %, about 75 mass % to about 80 mass %, about 80 mass % to about 85 mass %, about 85 mass % to about 90 mass %, or about 90 mass % to about 95 mass % relative to the combined mass of the coating formulation and the choline.
  • the choline may be present in an amount from about 50 mass % to about 60 mass %, about 50 mass % to about 65 mass %, about 50 mass % to about 70 mass %, about 50 mass % to about 75 mass %, about 50 mass % to about 80 mass %, about 50 mass % to about 85 mass %, about 50 mass % to about 90 mass %, about 55 mass % to about 95 mass %, about 60 mass % to about 95 mass %, about 65 mass % to about 95 mass %, about 70 mass % to about 95 mass %, about 75 mass % to about 95 mass %, about 80 mass % to about 95 mass %, or about 85 mass % to about 95 mass % relative to the combined weight of the vitamin C and the coating formulation.
  • the choline may be present in an amount of about 50 mass %, 55 mass %, 60 mass %, 65 mass %, 70 mass %, 75 mass %, 80 mass %, 85 mass %, 90 mass %, or about 95 mass % relative to the combined mass of the vitamin C and the coating formulation. In some exemplary embodiments, the choline may be present in an amount from about 75 mass % and about 85 mass % relative to the combined mass of the choline and the coating formulation.
  • multi-ingredient dosage forms that include a coating formulation of the present disclosure and at least one active ingredient.
  • the coating formulation of the present disclosure is used to coat the active ingredients described in Section IB above; however, the coating formulation preferably does not coat the entire dosage form.
  • the multi-ingredient dosage form includes additional ingredients, including vitamins, minerals, nutrients, supplements, drugs, excipients, fillers, binders, lubricants, plasticizers, etc.
  • the multi-ingredient dosage form may be a tablet, capsule, gummy, beverage, bar, suspension, granulation, powder, lozenge, troche, granule, pill, gel cap, or other dosage form known in the art.
  • the coating formulation may resist fracturing when the ingredients are compressed in the tablet.
  • the multi-ingredient dosage form may be modified to have a desired release profile.
  • the dosage form may be immediate release, controlled release, extended release, modified release, or sustained release.
  • the multi-ingredient dosage form includes a coating formulation of the present disclosure (see section IA of the detailed description herein).
  • the coating formulation includes shellac.
  • the coating formulation coats at least one active ingredient in the multi-ingredient dosage form (see section IB of the detailed description herein).
  • the at least one active ingredient may include vitamin C.
  • the vitamin C may include ascorbic acid, ferrous ascorbate, magnesium ascorbate, sodium ascorbate, calcium ascorbate, zinc ascorbate, molybdenum ascorbate, chromium ascorbate, manganese ascorbate, lithium ascorbate, potassium ascorbate, nickel ascorbate, silver ascorbate, or any other forms of vitamin C known in the art or combinations thereof.
  • the vitamin C is ascorbic acid.
  • the vitamin C may be present in an amount from about 50 mass % to about 95 mass % relative to the combined mass of the vitamin C and the coating formulation. In some aspects, the vitamin C may be present in an amount from about 50 mass % to about 55 mass %, about 55 mass % to about 60 mass %, about 60 mass % to about 65 mass %, about 65 mass % to about 70 mass %, about 70 mass % to about 75 mass %, about 75 mass % to about 80 mass %, about 80 mass % to about 85 mass %, about 85 mass % to about 90 mass %, or about 90 mass % to about 95 mass % relative to the combined mass of the vitamin C and the coating formulation.
  • the vitamin C may be present in an amount from about 50 mass % to about 60 mass %, about 50 mass % to about 65 mass %, about 50 mass % to about 70 mass %, about 50 mass % to about 75 mass %, about 50 mass % to about 80 mass %, about 50 mass % to about 85 mass %, about 50 mass % to about 90 mass %, about 55 mass % to about 95 mass %, about 60 mass % to about 95 mass %, about 65 mass % to about 95 mass %, about 70 mass % to about 95 mass %, about 75 mass % to about 95 mass %, about 80 mass % to about 95 mass %, or about 85 mass % to about 95 mass % relative to the combined weight of the vitamin C and the coating formulation.
  • the vitamin C may be present in an amount of about 50 mass %, 55 mass %, 60 mass %, 65 mass %, 70 mass %, 75 mass %, 80 mass %, 85 mass %, 90 mass %, or about 95 mass % relative to the combined mass of the vitamin C and the coating formulation. In some exemplary embodiments, the vitamin C may be present in an amount from about 70 mass % to about 80 mass % relative to the combined mass of the vitamin C and the coating formulation.
  • the vitamin C may be present in the mutli- ingredient dosage form in an amount from about 1 mg to about 2000 mg. In some aspects, the vitamin C may be present in the multi-ingredient dosage form in an amount from about 1 mg to about 250 mg, about 250 mg to about 500 mg, about 500 mg to about 750 mg, about 750 mg to about 1000 mg, about 1000 mg to about 1250 mg, about 1250 mg to about 1500 mg, about 1500 mg to about 1750 mg, about 1750 mg to about 2000 mg.
  • the vitamin C may be present in the multi-ingredient dosage form in an amount from about 1 mg to about 500 mg, about 1 mg to about 750 mg, about 1 mg to about 1000 mg, about 1 mg to about 1250 mg, about 1 mg to about 1500 mg, about 1 mg to about 1750 mg, about 250 mg to about 2000 mg, about 500 mg to about 2000 mg, about 750 mg to about 2000 mg, about 1000 mg to about 2000 mg, about 1250 mg to about 2000 mg, about 1500 mg to about 2000 mg, about 250 mg to about 1750 mg, about 500 mg to about 1500 mg, or about 750 mg to about 1250 mg.
  • the vitamin C may be present in the multi-ingredient dosage form in an amount of about 1 mg, 10 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, or about 2000 mg.
  • the at least one active ingredient may include choline.
  • the choline may include choline chloride, choline bitartrate, phosphatidyl choline, choline dihydrogen citrate, alpha glycerylphosphorylcholine, cytidine diphosphate-choline, choline folate, an ester of choline with DHA, esters of choline with 3-methyl-2-hexenoic acid (MHA), esters of choline with medium chain triglycerides, other esters of choline with fatty acids, other salts of choline, or any other forms of choline known in the art or combinations thereof.
  • the choline is choline bitartrate.
  • the choline may be present in an amount from about 50 mass % to about 95 mass % relative to the combined weight of the coating formulation and the choline. In some aspects, the choline may be present in an amount from about 50 mass % to about 55 mass %, about 55 mass % to about 60 mass %, about 60 mass % to about 65 mass %, about 65 mass % to about 70 mass %, about 70 mass % to about 75 mass %, about 75 mass % to about 80 mass %, about 80 mass % to about 85 mass %, about 85 mass % to about 90 mass %, or about 90 mass % to about 95 mass % relative to the combined mass of the coating formulation and the choline.
  • the choline may be present in an amount from about 50 mass % to about 60 mass %, about 50 mass % to about 65 mass %, about 50 mass % to about 70 mass %, about 50 mass % to about 75 mass %, about 50 mass % to about 80 mass %, about 50 mass % to about 85 mass %, about 50 mass % to about 90 mass %, about 55 mass % to about 95 mass %, about 60 mass % to about 95 mass %, about 65 mass % to about 95 mass %, about 70 mass % to about 95 mass %, about 75 mass % to about 95 mass %, about 80 mass % to about 95 mass %, or about 85 mass % to about 95 mass % relative to the combined weight of the vitamin C and the coating formulation.
  • the choline may be present in an amount of about 50 mass %, 55 mass %, 60 mass %, 65 mass %, 70 mass %, 75 mass %, 80 mass %, 85 mass %, 90 mass %, or about 95 mass % relative to the combined mass of the vitamin C and the coating formulation. In some exemplary embodiments, the choline may be present in an amount between about 75 mass % and about 85 mass % relative to the combined mass of the choline and the coating formulation.
  • the choline may be present in the mutli-ingredient dosage form in an amount of between about 1 mg to about 2000 mg.
  • the choline may be present in the multi-ingredient dosage form in an amount from about 1 mg to about 250 mg, about 250 mg to about 500 mg, about 500 mg to about 750 mg, about 750 mg to about 1000 mg, about 1000 mg to about 1250 mg, about 1250 mg to about 1500 mg, about 1500 mg to about 1750 mg, about 1750 mg to about 2000 mg.
  • the choline may be present in the multi-ingredient dosage form in an amount from about 1 mg to about 500 mg, about 1 mg to about 750 mg, about 1 mg to about 1000 mg, about 1 mg to about 1250 mg, about 1 mg to about 1500 mg, about 1 mg to about 1750 mg, about 250 mg to about 2000 mg, about 500 mg to about 2000 mg, about 750 mg to about 2000 mg, about 1000 mg to about 2000 mg, about 1250 mg to about 2000 mg, about 1500 mg to about 2000 mg, about 250 mg to about 1750 mg, about 500 mg to about 1500 mg, or about 750 mg to about 1250 mg.
  • the choline may be present in the multi-ingredient dosage form in an amount of about 1 mg, 10 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, or about 2000 mg.
  • the multi-ingredient dosage form may additionally include vitamins other than vitamin C.
  • the vitamins may include one or more of vitamin A (i.e., retinoids or carotene), vitamin D (i.e., calciferol), vitamin E (i.e., alphatocopherol), vitamin K (i.e., phylloquinone or menadione), vitamin B1 (i.e., thiamin), vitamin B2 (i.e., riboflavin), vitamin B3 (i.e., niacin), vitamin B5 (i.e., panteothenic acid), vitamin B6 (i.e., pyridoxine), vitamin B7 (i.e., biotin), vitamin B12 (i.e., cyanocobalamin), vitamin B9 (i.e., folate or folic acid), or other vitamins known by those having ordinary skill in the art.
  • vitamin A i.e., retinoids or carotene
  • vitamin D
  • the multi-ingredient dosage form may additionally include minerals.
  • the minerals may include calcium, chloride, chromium, copper, fluoride, iodine, iron, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, sodium, sulfur, zinc, or other minerals known by those having ordinary skill in the art or pharmaceutically acceptable salts thereof.
  • the multi-ingredient dosage form may additionally include supplements.
  • the supplements may include 5-hydroxytryptophan, antioxidants, amino acids, activated charcoal, ashwagandha, astaxanthin, astragalus, berberine, bromelain, chlorella, chlorophyll, chondroitin, coconut oil, cod liver oil, colloidal silver, conjugated linoleic acid, creatine, damiana, echinacea, emu oil, evening primrose oil, fenugreek, fiber, fish oil, gamma-aminobutyric acid, garlic, ginger, ginkgo, glucomannan, glucosamine, glutathione, gotu kola, hyaluronic acid, inositol, krill oil, licorice, lutein, maca, melatonin, moringa, omega fatty acids, prebiotics, probiotics, quercetin, rhodiola, saw palmet
  • the supplements may include
  • the multi-ingredient dosage form may additionally include excipients.
  • the excipients may include binders, plasticizers, fillers, bulking agents, disintegrating agents, glidants, lubricants, diluents, flavoring agents, odorizing agents, flavor-masking agents, odor-masking agents, anti-caking agents, preservatives, humectants, wetting agents, and other excipients known to those having skill in the art.
  • the multi-ingredient dosage form may include one or more additional active ingredients that are not coated by the coating formulation described herein.
  • the dosage forms of the present disclosure may show little or no spotting after about 18 days of storage at a temperature of 25°C and a relative humidity of 20%. Methods for measuring spotting are described in Section II below. For example, the dosage forms may show little or no spotting after about 18 days, 30 days, 60 days, 90 days, 120 days, 180 days, 250 days, or 300 days of storage at a temperature of 25°C and a relative humidity of 20%. The amount of spotting may be determined by colorimeter measurements as described herein.
  • the dosage forms of the present disclosure may show little or no spotting after about 18 days of storage at a temperature of 45°C and a relative humidity of 20%.
  • the dosage forms may show little or no spotting after about 18 days, 30 days, 60 days, 90 days, 120 days, 180 days, 250 days, or 300 days of storage at a temperature of 45°C and a relative humidity of 20%.
  • the amount of spotting may be determined by colorimeter measurements as described herein.
  • the dosage forms of the present disclosure may show little or no spotting after about 18 days of storage at a temperature of 25°C and a relative humidity of 30%.
  • the dosage forms may show little or no spotting after about 18 days, 30 days, 60 days, 90 days, 120 days, 180 days, 250 days, or 300 days of storage at a temperature of 25°C and a relative humidity of 30%.
  • the amount of spotting may be determined by colorimeter measurements as described herein.
  • the dosage forms of the present disclosure may show little or no spotting after about 18 days of storage at a temperature of 45°C and a relative humidity of 30%.
  • the dosage forms may show little or no spotting after about 18 days, 30 days, 60 days, 90 days, 120 days, 180 days, 250 days, or 300 days of storage at a temperature of 45°C and a relative humidity of 30%.
  • the amount of spotting may be determined by colorimeter measurements as described herein.
  • the multi-ingredient dosage form may be suitable for administration to a subject.
  • the subject may a human, such as an adult or a child.
  • the method includes providing at least one active ingredient that includes at least one of vitamin C and choline, coating the at least one active ingredient in an coating formulation comprising shellac, and including the at least one active ingredient coated in the coating formulation in a dosage form.
  • the coating formulation may be any coating formulation of the present disclosure described in Section I.
  • the step of coating the at least one active ingredient in a coating formulation comprising shellac may be accomplished through pan coating, fluid bed coating, spray blending, or other coating methods known in the art.
  • the amount of spotting in a dosage form may be determined by a visual determination or by colorimetric measurements.
  • a colorimeter may be used to measure the amount of spotting in a dosage form by comparing it to a reference dosage form of the same composition.
  • the color change may be measured by determining the total color difference (AE) of the dosage form compared to the reference dosage form, or by other methods known in the art, wherein a AE of 0 indicates no color change.
  • the average AE in a dosage form may be about 2.5 or less, or more preferably about 1 .0 or less.
  • the AE may be about 2.5, 2.4, 2.3, 2.2, 2.1 , 2.0, 1 .9, 1 .8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1 , 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1 , or less than 0.1 .
  • a AE of less than 1 .0 is generally considered a visually imperceptible color change.
  • a dosage form with “little spotting” refers to a dosage form with a AE of 2.5 or less as compared to a reference dosage form; a dosage form with “no spotting” refers to a dosage form with a AE of 1 .0 or less as compared to a reference dosage form.
  • the dosage forms of the present disclosure may show little or no spotting after about 18 days of storage at a temperature of 25°C and a relative humidity of 20%.
  • the dosage forms may show little or no spotting after about 18 days, 30 days, 60 days, 90 days, 120 days, 180 days, 250 days, or 300 days of storage at a temperature of 25°C and a relative humidity of 20%.
  • the amount of spotting may be determined by colorimeter measurements as described herein.
  • the dosage forms of the present disclosure may show little or no spotting after about 18 days of storage at a temperature of 45°C and a relative humidity of 20%.
  • the dosage forms may show little or no spotting after about 18 days, 30 days, 60 days, 90 days, 120 days, 180 days, 250 days, or 300 days of storage at a temperature of 45°C and a relative humidity of 20%.
  • the amount of spotting may be determined by colorimeter measurements as described herein.
  • the dosage forms of the present disclosure may show little or no spotting after about 18 days of storage at a temperature of 25°C and a relative humidity of 30%.
  • the dosage forms may show little or no spotting after about 18 days, 30 days, 60 days, 90 days, 120 days, 180 days, 250 days, or 300 days of storage at a temperature of 25°C and a relative humidity of 30%.
  • the amount of spotting may be determined by colorimeter measurements as described herein.
  • the dosage forms of the present disclosure may show little or no spotting after about 18 days of storage at a temperature of 45°C and a relative humidity of 30%.
  • the dosage forms may show little or no spotting after about 18 days, 30 days, 60 days, 90 days, 120 days, 180 days, 250 days, or 300 days of storage at a temperature of 45°C and a relative humidity of 30%.
  • the amount of spotting may be determined by colorimeter measurements as described herein.
  • the coating formulations of the present disclosure may be manufactured by methods known in the art.
  • the coating formulation may be made by dissolving the shellac and other coating formulation ingredients described in Section I above in a suitable solvent, such as an alcohol solvent.
  • a suitable solvent such as an alcohol solvent.
  • the solvent may be ethanol.
  • the active ingredient may be provided in a particulate form (e.g., a granule).
  • the active ingredient may include choline or vitamin C, or any other active ingredient provided in Section I.
  • the coating formulation may then be applied to the active ingredient using coating methods known in the art, such as pan coating, spray coating, etc.
  • coating methods known in the art, such as pan coating, spray coating, etc.
  • the coating formulation is applied to the active ingredient, thus forming a coated composition.
  • the coated composition may be sieved to adjust the average particle size of the coated composition.
  • the dosage forms may be manufactured by various methods known to those having skill in the art.
  • the dosage form may be tablet, capsule, gummy, beverage, bar, suspension, granulation, powder, lozenge, troche, granule, pill, gel cap or other solid dosage forms known to those having skill in the art.
  • the dosage form is a tablet.
  • the coated compositions may be incorporated into the dosage forms using methods known to those having ordinary skill in the art. For example, the coated composition may be combined with other ingredients and compressed to form a tablet. It will be appreciated that some unit operations may be modified or excluded to prevent damage to the coating formulation. For example, milling the dosage form may be excluded to prevent damaging the coating formulation. C. Methods of Administration
  • the methods may include orally, sublingually, or buccally administering a dosage form of the present disclosure to a subject.
  • the subject may a human, such as an adult or a child.
  • the subject may have a nutritive deficiency or insufficiency, such as a vitamin C deficiency, a choline deficiency, or both.
  • the methods may be suitable for supplementing nutrition to a subject.
  • Embodiment 1 A coating formulation comprising shellac, wherein the coating formulation coats at least one active ingredient in a multi-ingredient dosage form.
  • Embodiment 2 The coating formulation of embodiment 1 , wherein the at least one active ingredient has a concentration of between about 50.0 mass % to about 95.0 mass % relative to the total mass of the at least one active ingredient and the coating formulation.
  • Embodiment 3 The coating formulation of embodiment 1 or embodiment 2, wherein the at least one active ingredient comprises vitamin C.
  • Embodiment 4 The coating formulation of embodiment 3, wherein the vitamin C is selected from the group consisting of ascorbic acid, ferrous ascorbate, magnesium ascorbate, sodium ascorbate, calcium ascorbate, zinc ascorbate, molybdenum ascorbate, chromium ascorbate, manganese ascorbate, lithium ascorbate, potassium ascorbate, nickel ascorbate, silver ascorbate, and any combination thereof.
  • the vitamin C is selected from the group consisting of ascorbic acid, ferrous ascorbate, magnesium ascorbate, sodium ascorbate, calcium ascorbate, zinc ascorbate, molybdenum ascorbate, chromium ascorbate, manganese ascorbate, lithium ascorbate, potassium ascorbate, nickel ascorbate, silver ascorbate, and any combination thereof.
  • Embodiment 5 The coating formulation of embodiment 3 or embodiment 4, wherein the vitamin C is present in an amount from about 50 mass % to about 95 mass % relative to the combined mass of the vitamin C and the coating formulation.
  • Embodiment 6 The coating formulation of any one of embodiments 1 -5, wherein the at least one active ingredient comprises choline.
  • Embodiment 7 The coating formulation of claim 6, wherein the choline is selected from the group consisting of choline chloride, choline bitartrate, phosphatidyl choline, choline dihydrogen citrate, alpha glycerylphosphorylcholine, cytidine diphosphate-choline, choline folate, an ester of choline with DHA, esters of choline with 3-methyl-2-hexenoic acid (MHA), esters of choline with medium chain triglycerides, other esters of choline with fatty acids, other salts of choline, or combinations thereof.
  • MHA 2-methyl-2-hexenoic acid
  • Embodiment 8 The coating formulation of embodiment 6 or embodiment 7, wherein the choline is present in an amount from about 50 mass % to about 95 mass % relative to the combined mass of the choline and the coating formulation.
  • Embodiment 9 The coating formulation of any one of embodiments 1 -8, wherein the shellac is present in an amount from about 1 mass % to about 50 mass % relative to the combined mass of the at least one active ingredient and the coating formulation.
  • Embodiment 10 The coating formulation of any one of embodiments 1 -9, wherein the coating formulation further comprises a silicate.
  • Embodiment 11 The coating formulation of embodiment 10, wherein the silicate includes silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or combinations thereof.
  • the silicate includes silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or combinations thereof.
  • Embodiment 12 The coating formulation of embodiment 10 or embodiment 11 , wherein the silicate is present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • Embodiment 13 The coating formulation of embodiment 11 , wherein the silicon dioxide includes colloidal silicon dioxide or fumed silica.
  • Embodiment 14 The coating formulation of any one of embodiments 1 -13, wherein the coating formulation further comprises cellulose or a derivative thereof.
  • Embodiment 15 The coating formulation of embodiment 14, wherein the cellulose or a derivative thereof includes microcrystalline cellulose, powdered cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hypromellose, carboxymethylcellulose, or combinations thereof.
  • Embodiment 16 The coating formulation of embodiment 14 or embodiment 15, wherein the cellulose or a derivative thereof comprises hydroxypropylcellulose.
  • Embodiment 17 The coating formulation of embodiment 16, wherein the hydroxypropylcellulose is present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • Embodiment 18 The coating formulation of embodiment 14 or embodiment 15, wherein the cellulose or a derivative thereof comprises microcrystalline cellulose.
  • Embodiment 19 The coating formulation of embodiment 18, wherein the microcrystalline cellulose is present in the coating formulation in an amount from about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the first active ingredient and second active ingredient.
  • Embodiment 20 The coating formulation of embodiment 14 or embodiment 15, wherein the cellulose or a derivative thereof comprises ethylcellulose.
  • Embodiment 21 The coating formulation of embodiment 20, wherein the ethylcellulose is present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the first active ingredient or the second active ingredient.
  • Embodiment 22 The coating formulation of any one of embodiments 1 -21 , wherein the coating formulation further comprises starch.
  • Embodiment 23 The coating formulation of embodiment 22, wherein the starch includes maize starch, potato starch, rice starch, wheat starch, tapioca starch, or combinations thereof.
  • Embodiment 24 The coating formulation of embodiment 22 or embodiment 23, wherein the starch is present in the coating formulation in an amount from about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the first active ingredient or the second active ingredient.
  • Embodiment 25 A multi-ingredient dosage form, the dosage form comprising: at least one active ingredient; and a coating formulation comprising shellac, wherein the coating formulation coats the at least one active ingredient.
  • Embodiment 26 The dosage form of embodiment 25, wherein the at least one active ingredient comprises vitamin C.
  • Embodiment 27 The dosage form of embodiment 26, wherein the vitamin C is present in the dosage form in an amount of about 1 mg to about 2000 mg.
  • Embodiment 28 The dosage form of embodiment 26 or embodiment
  • vitamin C is selected from the group consisting of ascorbic acid, ferrous ascorbate, magnesium ascorbate, sodium ascorbate, calcium ascorbate, zinc ascorbate, molybdenum ascorbate, chromium ascorbate, manganese ascorbate, lithium ascorbate, potassium ascorbate, nickel ascorbate, silver ascorbate, and any combination thereof.
  • Embodiment 29 The dosage form of any one of embodiments 25-
  • the at least one active ingredient comprises choline.
  • Embodiment 30 The dosage form of embodiment 29, wherein the choline is present in the dosage form in an amount from about 1 mg to about 2000 mg.
  • Embodiment 31 The dosage form of embodiment 29 or embodiment
  • the choline is selected from the group consisting of choline chloride, choline bitartrate, phosphatidyl choline, choline dihydrogen citrate, alpha glycerylphosphorylcholine, cytidine diphosphate-choline, choline folate, an ester of choline with DHA, esters of choline with 3-methyl-2-hexenoic acid (MHA), esters of choline with medium chain triglycerides, other esters of choline with fatty acids, other salts of choline, or combinations thereof.
  • MHA 3-methyl-2-hexenoic acid
  • Embodiment 32 The dosage form of any one of embodiments 25-
  • the shellac is present in an amount from about 1 mass % to about 50 mass % relative to the total mass of the at least one active ingredient and the coating formulation.
  • Embodiment 33 The dosage form of any one of embodiments 25-
  • the at least one active ingredient is present in an amount from about 50.0 mass % to about 95.0 mass % relative to the combined mass of the at least one active ingredient and the coating formulation.
  • Embodiment 34 The dosage form of any one of embodiments 25- 33, wherein the at least one active ingredient comprises vitamin C and choline, and wherein the choline is not coated by the coating formulation.
  • Embodiment 35 The dosage form of any one of embodiments 25- 33, wherein the at least one active ingredient comprises choline and the dosage form further comprises vitamin C, wherein the vitamin C is not coated by the coating formulation.
  • Embodiment 36 The dosage form of any one of embodiments 25- 33, wherein the at least one active ingredient comprises vitamin C and the dosage form further comprises choline, wherein the choline is not coated by the coating formulation.
  • Embodiment 37 The dosage form of any one of embodiments 25-
  • the dosage form is a tablet, capsule, gummy, beverage, bar, suspension, granulation, powder, lozenge, troche, granule, pill, gel cap.
  • Embodiment 38 The dosage form of any one of embodiments 25-
  • the dosage form further comprises at least one of vitamins, minerals, supplements, and excipients.
  • Embodiment 39 The dosage form of any one of embodiments 25-
  • the dosage form further comprises an additional active ingredient that is that is not coated by the coating formulation.
  • Embodiment 40 The dosage form of any one of embodiments 25-
  • the coating formulation further comprises a silicate.
  • Embodiment 41 The dosage form of embodiment 40, wherein the silicate includes silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or combinations thereof.
  • the silicate includes silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or combinations thereof.
  • Embodiment 42 The dosage form of embodiment 40 or embodiment 41 , wherein the silicate is present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • Embodiment 43 The dosage form of embodiment 41 , wherein the silicon dioxide includes colloidal silicon dioxide or fumed silica.
  • Embodiment 44 The dosage form of any one of embodiments 25- 43, wherein the coating formulation further comprises cellulose or a derivative thereof.
  • Embodiment 45 The dosage form of embodiment 44, wherein the cellulose or a derivative thereof includes microcrystalline cellulose, powdered cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hypromellose, carboxymethylcellulose, or combinations thereof.
  • Embodiment 46 The dosage form of embodiment 44 or embodiment
  • the cellulose or a derivative thereof comprises hydroxypropylcellulose.
  • Embodiment 47 The dosage form of embodiment 46, wherein the hydroxypropylcellulose is present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • Embodiment 48 The dosage form of embodiment 44 or embodiment
  • cellulose or a derivative thereof comprises microcrystalline cellulose.
  • Embodiment 49 The dosage form of embodiment 48, wherein the microcrystalline cellulose is present in the coating formulation in an amount from about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the first active ingredient and second active ingredient.
  • Embodiment 50 The dosage form of embodiment 44 or embodiment
  • the cellulose or a derivative thereof comprises ethylcellulose.
  • Embodiment 51 The dosage form of embodiment 50, wherein the ethylcellulose is present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the first active ingredient or the second active ingredient.
  • Embodiment 52 The dosage form of any one of embodiments 25- 51 , wherein the coating formulation further comprises starch.
  • Embodiment 53 The dosage form of embodiment 52, wherein the starch includes maize starch, potato starch, rice starch, wheat starch, tapioca starch, or combinations thereof.
  • Embodiment 54 The dosage form of embodiment 52 or embodiment
  • starch is present in the coating formulation in an amount from about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the first active ingredient or the second active ingredient.
  • Embodiment 55 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 18 days at 25°C and 20% relative humidity.
  • Embodiment 56 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 60 days at 25°C and 20% relative humidity.
  • Embodiment 57 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 120 days at 25°C and 20% relative humidity.
  • Embodiment 58 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 18 days at 45°C and 20% relative humidity.
  • Embodiment 59 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 60 days at 45°C and 20% relative humidity.
  • Embodiment 60 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 120 days at 45°C and 20% relative humidity.
  • Embodiment 61 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 18 days at 25°C and 30% relative humidity.
  • Embodiment 62 The dosage form of any one of embodiments 25-
  • Embodiment 63 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 120 days at 25°C and 30% relative humidity.
  • Embodiment 64 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 18 days at 45°C and 30% relative humidity.
  • Embodiment 65 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 60 days at 45°C and 30% relative humidity.
  • Embodiment 66 The dosage form of any one of embodiments 25-
  • the multi-ingredient dosage form shows little spotting after storage for about 120 days at 45°C and 30% relative humidity.
  • Embodiment 67 A multi-ingredient dosage form, the dosage form comprising: choline; vitamin C; and a coating formulation comprising shellac, wherein the coating formulation coats the choline.
  • Embodiment 68 A multi-ingredient dosage form, the dosage form comprising: choline; vitamin C; and a coating formulation comprising shellac, wherein the coating formulation coats the vitamin C.
  • Embodiment 69 A multi-ingredient dosage form, the dosage form comprising: choline, wherein the choline is coated by a first coating formulation comprising shellac; and vitamin C, wherein the vitamin C is coated by a second coating formulation comprising shellac.
  • Embodiment 70 A method of preventing spotting in a dosage form, the method comprising: providing an active ingredient comprising at least one of vitamin C and choline; coating the active ingredient in a coating formulation comprising shellac; and including the active ingredient coated in the coating formulation in a dosage form.
  • Embodiment 71 The method of embodiment 70, wherein the active ingredient is vitamin C.
  • Embodiment 72 The method of embodiment 70 or embodiment 71 , wherein the active ingredient is choline.
  • Embodiment 73 The method of any one of embodiments 70-72, wherein the active ingredient is choline and vitamin C.
  • Embodiment 74 The method of any one of embodiments 70-73, wherein the coating formulation further comprises a silicate.
  • Embodiment 75 The method of embodiment 74, wherein the silicate includes silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or combinations thereof.
  • Embodiment 76 The method of embodiment 74 or embodiment 75, wherein the silicate is present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • Embodiment 77 The method of embodiment 75, wherein the silicon dioxide includes colloidal silicon dioxide or fumed silica.
  • Embodiment 78 The method of any one of embodiments 70-77, wherein the coating formulation further comprises cellulose or a derivative thereof.
  • Embodiment 79 The method of embodiment 78, wherein the cellulose or a derivative thereof includes microcrystalline cellulose, powdered cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hypromellose, carboxymethylcellulose, or combinations thereof.
  • Embodiment 80 The method of embodiment 78 or embodiment 79, wherein the cellulose or a derivative thereof comprises hydroxypropylcellulose.
  • Embodiment 81 The method of embodiment 80, wherein the hydroxypropylcellulose is present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the at least one active ingredient.
  • Embodiment 82 The method of embodiment 78 or embodiment 79, wherein the cellulose or a derivative thereof comprises microcrystalline cellulose.
  • Embodiment 83 The method of embodiment 82, wherein the microcrystalline cellulose is present in the coating formulation in an amount from about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the first active ingredient and second active ingredient.
  • Embodiment 84 The method of embodiment 78 or embodiment 79, wherein the cellulose or a derivative thereof comprises ethylcellulose.
  • Embodiment 85 The method of embodiment 84, wherein the ethylcellulose is present in the coating formulation in an amount from about 0 mass % to about 10 mass % relative to the combined mass of the coating formulation and the first active ingredient or the second active ingredient.
  • Embodiment 86 The method of any one of embodiments 70-85, wherein the coating formulation further comprises starch.
  • Embodiment 87 The method of embodiment 86, wherein the starch includes maize starch, potato starch, rice starch, wheat starch, tapioca starch, or combinations thereof.
  • Embodiment 88 The method of embodiment 86 or embodiment 87, wherein the starch is present in the coating formulation in an amount from about 0 mass % to about 25 mass % relative to the combined mass of the coating formulation and the first active ingredient or the second active ingredient.
  • Embodiment 89 The method of any one of embodiments 70-88, wherein the multi-ingredient dosage form shows little spotting after storage for about 18 days at 25°C and 20% relative humidity.
  • Embodiment 90 The method of any one of embodiments 70-89, wherein the multi-ingredient dosage form shows little spotting after storage for about 60 days at 25°C and 20% relative humidity.
  • Embodiment 91 The method of any one of embodiments 70-90, wherein the multi-ingredient dosage form shows little spotting after storage for about 120 days at 25°C and 20% relative humidity.
  • Embodiment 92 The method of any one of embodiments 70-91 , wherein the multi-ingredient dosage form shows little spotting after storage for about 18 days at 45°C and 20% relative humidity.
  • Embodiment 93 The method of any one of embodiments 70-92, wherein the multi-ingredient dosage form shows little spotting after storage for about 60 days at 45°C and 20% relative humidity.
  • Embodiment 94 The method of any one of embodiments 70-93, wherein the multi-ingredient dosage form shows little spotting after storage for about 120 days at 45°C and 20% relative humidity.
  • Embodiment 95 The method of any one of embodiments 70-94, wherein the multi-ingredient dosage form shows little spotting after storage for about 18 days at 25°C and 30% relative humidity.
  • Embodiment 96 The method of any one of embodiments 70-95, wherein the multi-ingredient dosage form shows little spotting after storage for about 60 days at 25°C and 30% relative humidity.
  • Embodiment 97 The method of any one of embodiments 70-96, wherein the multi-ingredient dosage form shows little spotting after storage for about 120 days at 25°C and 30% relative humidity.
  • Embodiment 98 The method of any one of embodiments 70-97, wherein the multi-ingredient dosage form shows little spotting after storage for about 18 days at 45°C and 30% relative humidity.
  • Embodiment 99 The method of any one of embodiments 70-98, wherein the multi-ingredient dosage form shows little spotting after storage for about 60 days at 45°C and 30% relative humidity.
  • Embodiment 100 The method of any one of embodiments 70-99, wherein the multi-ingredient dosage form shows little spotting after storage for about 120 days at 45°C and 30% relative humidity.
  • Example 1 Exemplary Dosage Form
  • a dosage form of the present disclosure was made that included the following ingredients: vitamin A, vitamin D, biotin, magnesium stearate, vitamin K1 , thiamine, riboflavin, niacin, vitamin B6, folic acid, vitamin B12, pantothenic acid, calcium, magnesium oxide, potassium chloride, iodine, phosphorous, ferrous fumarate, zinc oxide, copper oxide, manganese sulfate, molybdenum, chromium, picolinate, choline bitartrate, and vitamin C.
  • This formulation was used to test different coating formulations of the present disclosure. The formulation was modified in some cases to include choline. When the formulation did not include choline, hydroxypropyl cellulose was included in the formulation in the same amount, i.e., 280 mg. The amounts of each component in the formulation are shown in Table 1 .
  • FIG. 1 shows a tablet that contained vitamin C but no choline under different storage conditions after 18 days.
  • the tablet composition is shown in Table 2.
  • the storage conditions ranged from 10% relative humidity (RH) to 30% RH, and 25°C to 45°C. Spotting occurred under each storage condition to some degree, with the most noticeable spotting occurring at high temperature and humidity.
  • RH relative humidity
  • RH relative humidity
  • FIGS. 2A-2D shows commercially available tablets that were stored in different conditions for 18 days.
  • the tablets in FIGS. 2A, 2B, and 2D did not contain any choline, whereas the tablet in FIG. 2C contained 30 mg of choline. All tablets contained vitamin C.
  • the tablets were cut in half for the experiment.
  • the tablet halves labelled “open” and “initial” were two halves of the same tablet, and the tablet labelled “capped” was a half of a separate tablet.
  • the tablets labelled “open” were stored in at 40°C and 75% RH for 24 hours.
  • the tablets labelled “capped” were also stored at 40°C and 75% RH for 24 hours but were covered with a cap inside the humidity chamber.
  • the tablets labelled “initial” were stored at room temperature and 0% RH. Each tablet showed severe spotting in the “open” conditions.
  • FIG. 3 shows the spotting for a tablet containing choline and vitamin C stored under different temperature and humidity conditions for 18 days.
  • the tablet composition is shown in Table 3.
  • the temperature conditions tested were 25°C, 45°C, 65°C, and 85°C, and the relative humidity conditions tested were 0%, 10%, 30%, and 60%.
  • spotting accelerated as temperature and humidity increased.
  • the tablet was almost entirely black after 18 days, regardless of the temperature. Table 3
  • FIG. 4 shows spotting for a tablet containing choline and vitamin C under refrigerated conditions.
  • the tablet had the composition of the tablet described in Table 3.
  • the tablets were stored at 4°C for 18 days at 0% RH, 30% RH, and 60% RH. After 18 days, even in refrigerated conditions, the tablet stored at 60% RH still exhibited severe spotting.
  • FIGS. 5A and 5B show spotting for a tablet containing vitamin C and various forms of choline as compared to a tablet containing no choline.
  • the general tablet composition is described in Table 4. The tablets were stored for 18 days at temperatures of either 25°C or 45°C and a relative humidity of either 10% or 30%.
  • One tablet containing no choline was used as a reference.
  • FIG. 5A shows the reference tablet and tablets containing choline chloride and choline bitartrate.
  • FIG. 5B shows tablets containing choline chloride crystals blended with 1.5% calcium chloride, choline chloride crystals blended with 1 .5% trimagnesiumcitrate, and choline chloride blended with 2% magnesium stearate.
  • choline chloride crystals blended with 1 .5% calcium chloride means that the choline chloride crystals are blended with 1 .5% w/w of calcium chloride in relation to the combined mass of the choline chloride and the coating. Stated another way, every 98.5 mg of choline chloride in the tablet is blended with 1 .5 mg of calcium chloride. As can clearly be seen from FIGS. 5A- 5B, spotting occurred under nearly all storage conditions with the addition of the various forms of choline. Additionally, the figures suggest that generally the relative humidity has a large effect on the degree of spotting.
  • FIG. 6A shows spotting for a tablet including various forms of vitamin C (VitC) and choline in the form of choline bitartrate.
  • the general composition of the tablets is provided in Table 5.
  • a tablet containing no vitamin C is used as a reference.
  • the tablets were stored for 18 days at temperatures of 25°C or 45°C and at a relative humidity of 10%, 20%, or 30%.
  • the tablets tested in order from top to bottom of FIG. 6A included vitamin C in a matrix of alginate beads, vitamin C in a matrix of ethylcellulose, vitamin C in a matrix of vegetable mono- and diglycerides (60% vitamin C), vitamin C in the form of calcium ascorbate, and a commercial vitamin C formulation containing ascorbic acid, soybean oil, and silicon dioxide.
  • increased temperature and relative humidity increased the degree of spotting for all of the various vitamin C forms. Some degree of spotting occurred at all temperature and humidity conditions.
  • Table 5 shows spotting for a tablet including various forms of vitamin C (Vit
  • FIG. 6B shows spotting for a tablet containing vitamin C and choline and various coating formulations.
  • the tablet compositions are described in Table 3.
  • the tablets were stored for 18 days at temperatures of 25°C or 45°C and at a relative humidity of 20% or 30%.
  • 6B included vitamin C blended with 3.8% citrus bioflavonoids and 3.3% fatty acids, vitamin C coated in a mixture of 0.13% oleic acid, 1.12% ethyl cellulose, 0.02% medium-chain triglycerides, 0.03% glycerin, and 1% calcium stearate (OEMGC), vitamin C blended with 50% carnauba wax (CB), vitamin C blended with 60% carnauba wax (CB), and vitamin C blended with ethylcellulose. Although the spotting was greatly reduced in comparison to previous trials, the tablets still exhibited some degree of spotting.
  • OEMGC calcium stearate
  • FIG. 7 shows spotting for a tablet containing both vitamin C and choline and various coating formulations.
  • the tablet compositions are described in Table 3.
  • the tablets were stored for 18 days at temperatures of 25°C or 45°C and at a relative humidity of 20% or 30%.
  • the tablets tested in order from top to bottom of FIG. 7 included a tablet containing choline bitartrate coated with a mixture of shellac and talc, a tablet containing vitamin C coated with a mixture of shellac and talc, a tablet containing vitamin C and choline bitartrate both coated in a mixture of shellac and talc, and a tablet containing choline bitartrate and vitamin C without a coating. It is clear from FIG.
  • FIG. 8 shows the progression of spotting for a tablet containing both vitamin C and choline and coating formulations that included a mixture of shellac and talc.
  • the tablet compositions are described in Table 3.
  • the tablets were stored for 18 days at temperatures of 25°C or 45°C and at a relative humidity of 30%. No spotting was observed for any of the tablets.
  • talc cannot be used for certain pharmaceutical applications.
  • more coating formulations were developed that did not contain talc to be used for pharmaceutical applications.
  • FIG. 9 shows the progression of spotting for a tablet containing shellac coatings on vitamin C or on choline bitartrate.
  • the tablet compositions are described in Table 3. The percentages refer to the weight percent of the active ingredient relative to the combined weight of the active ingredient and the coating; i.e., the tablet labeled “Shellac-VitC (87%)” means that the tablet contained 87% vitamin C by weight and 13% coating by weight.
  • the shellac coating did not contain any other additives such as talc; i.e., the coating contained only shellac.
  • the tablets were stored for 18 days at temperatures of 25°C or 45°C and at a relative humidity of 20% or 30%. The images show the tablets on days 0, 4, 7, 11 , 14, and 18. The tablets containing 87% vitamin C coated in shellac showed spotting at only high temperature and humidity. However, the remaining tablets showed little to no spotting.
  • FIG. 10 shows the progression of spotting for a tablet containing shellac coatings on vitamin C or on choline bitartrate.
  • the tablet compositions are described in Table 3.
  • the tablets were stored for 18 days at temperatures of 25°C or 45°C and at a relative humidity of 20% or 30%.
  • the images show the tablets on days 0, 4, 7, 11 , 14, and 18. Tablets that included no vitamin C and uncoated ascorbic acid were included for reference.
  • the tablets that included shellac-coated vitamin C and choline bitartrate showed little to no spotting.
  • FIG. 11 shows the progression of spotting for a tablet containing shellac coatings on vitamin C or on choline bitartrate, or on both.
  • the tablet compositions are described in Table 3.
  • the tablets were stored for 18 days at a temperature of 45°C and at a relative humidity of 20% or 30%.
  • the images show the tablets on days 0, 4, 7, 11 , 14, and 18. It can clearly be seen that tablets that contained choline bitartrate and vitamin C coated in shellac showed no spotting. Moreover, tablets that contained either choline bitartrate coated in shellac or vitamin C coated in shellac still exhibited little or no spotting.
  • Coating formulations were made to coat choline bitartrate and ascorbic acid (vitamin C) within a dosage form.
  • Table 6 shows different formulations that were made.
  • a HunterLab UltraScan VIS colorimeter was used to perform colorimetric analysis on the tablets. One or more of each tablet tested was reserved to be used as the initial colorimeter measurement. The reserved tablet(s) was stored in the dark in a desiccator to prevent spotting.
  • FIGS. 12A-12G show the colorimeter measurements for tablets containing a coating formulation of the present disclosure. All tablets were stored at 30% RH for 18 days.
  • FIG 12A shows the colorimeter measurements from a tablet containing coating formulations 1 and 4 described in Table 6.
  • FIG. 12B shows the colorimeter measurements from a tablet containing coating formulations 1 and 5 described in Table 6.
  • FIG. 12C shows the colorimeter measurements from a tablet containing coating formulations 2 and 4 described in Table 6.
  • FIG. 12D shows the colorimeter measurements from a tablet containing coating formulations 2 and 5 described in Table 6.
  • FIG. 12E shows the colorimeter measurements from a tablet containing coating formulations 3 and 4 described in Table 6.
  • FIG. 12F shows the colorimeter measurements from a tablet containing coating formulations 3 and 5 described in Table 6.
  • FIG. 12G shows the colorimeter measurements from a tablet containing coating formulations 1 and 5 described in Table 6, plus talc. Colorimeter measurements were conducted at various times over the course of 18 days.
  • FIG. 13 shows the each of the tablets measured in FIGS. 12A-12G, the AE measured on days 0, 4, 7, 11 , 14, and 18, as well as the average AE measured for each tablet. Overall, the average AE ranged from 0.85 to 2.03, indicating a low degree of color change among the tablets.
  • FIGS. 14A-14B show colorimeter measurements for tablets that did not contain coating formulations of the present disclosure.
  • FIG. 14A shows the colorimeter measurements for a tablet that contained vitamin C and no choline.
  • FIG. 14B shows the colorimeter measurements from a tablet containing vitamin C and choline chloride. It is clear that the tablets measured in FIGS. 14A-14B showed far greater color change compared to the tablets shown in FIGS. 12A-12G.
  • tablets without a coating formulation of the present disclosure had an average AE of about 7-10. In one tablet that included choline chloride coated with calcium chloride, the AE on day 18 was 68.7, showing a large color change from the reference tablet.
  • FIG. 14C shows the solutions used for the colorimeter experiments of FIGS. 14A-14B after 18 days.
  • the cuvettes on the left side are the samples for tablets that contained vitamin C and no choline.
  • the cuvettes on the right side are the samples for tablets that contained vitamin C and choline chloride.

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
PCT/US2023/064173 2022-03-11 2023-03-10 Intra-dosage form coatings and applications thereof Ceased WO2023173111A2 (en)

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CN202380024059.1A CN118946346A (zh) 2022-03-11 2023-03-10 剂型内包衣和其应用
US18/845,997 US20250073175A1 (en) 2022-03-11 2023-03-10 Intra-Dosage Form Coatings and Applications Thereof
JP2024548573A JP2025506698A (ja) 2022-03-11 2023-03-10 剤形内コーティング及びその適用
KR1020247027473A KR20250023329A (ko) 2022-03-11 2023-03-10 투여 형태 내부의 코팅 및 이의 적용
EP23767759.6A EP4489731A4 (en) 2022-03-11 2023-03-10 INTERNAL COATINGS OF GALENIC FORMS AND THEIR APPLICATIONS

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US202263318946P 2022-03-11 2022-03-11
US63/318,946 2022-03-11

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WO2023173111A3 WO2023173111A3 (en) 2023-12-07

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EP (1) EP4489731A4 (https=)
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GB0007419D0 (en) * 2000-03-27 2000-05-17 Smithkline Beecham Gmbh Composition
US20070292508A1 (en) * 2006-06-05 2007-12-20 Balchem Corporation Orally disintegrating dosage forms
CA3013795A1 (en) * 2016-02-17 2017-08-24 Corr-Jensen Inc. Time release vitamins and minerals in edible oils
US20220193033A1 (en) * 2019-04-30 2022-06-23 Dsm Ip Assets B.V. New delivery system for specific water-soluble vitamins

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EP4489731A4 (en) 2026-03-11
EP4489731A2 (en) 2025-01-15
KR20250023329A (ko) 2025-02-18
WO2023173111A3 (en) 2023-12-07
US20250073175A1 (en) 2025-03-06
CN118946346A (zh) 2024-11-12
JP2025506698A (ja) 2025-03-13

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