In-dosage form coatings and their applications

Abstract

The present disclosure relates to a coating formulation for use with a multi-component dosage form containing vitamin C and / or choline. The coating formulation surrounds the vitamin C and / or choline in the multi-component dosage form, which prevents spotting of the dosage form.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 318,946, entitled "INTRA-DOSAGE FORM COATINGS AND APPLICATIONS THEREOF," filed March 11, 2022, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to coating formulations and methods of use and preparation thereof. Thus, the present disclosure relates to the fields of chemistry, pharmacy, and nutraceuticals. [Background technology]

[0003] Choline is an essential nutrient present in many foods. Choline is available in dietary supplements, but is rarely included in dosage forms such as multivitamins containing vitamin C. This is generally due to the hygroscopic nature of choline. When vitamin C decomposes, it causes black spots on the surface of the dosage form, making the dosage form unattractive to consumers. Furthermore, this also reduces the potency of vitamin C in the dosage form, forcing manufacturers to overformulate the dosage form or risk failing the vitamin C label claim.

[0004] When choline is present in the dosage form, it absorbs moisture from the air or from other components in the dosage form, accelerating the decomposition of vitamin C. In addition, the presence of metals and metal oxides in the dosage form accelerates the decomposition of vitamin C. Furthermore, other agents in the dosage form, such as magnesium oxide, ferrous fumarate, and dicalcium phosphate, can also accelerate spotting, which accelerates the spotting caused by the decomposition of vitamin C.

[0005] What is needed is a dosage form that includes vitamin C and optionally choline, which reduces the rate of decomposition of vitamin C to prevent spotting. Summary of the Invention

[0006] Provided herein is a coating formulation comprising shellac, which when coated onto at least one active ingredient in a multi-component dosage form, prevents spotting in the dosage form. In some embodiments, the at least one active ingredient has a concentration of about 50.0% to about 95.0% by weight, based on the total weight of the at least one active ingredient and the coating formulation.

[0007] In some embodiments, the at least one active ingredient comprises vitamin C. In some aspects, 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. In some additional aspects, the vitamin C is present in an amount of about 50% to about 95% by weight based on the combined weight of the vitamin C and the coating formulation.

[0008] In some embodiments, the at least one active ingredient comprises choline. In some embodiments, the choline is selected from the group consisting of choline chloride, choline bitartrate, phosphatidylcholine, choline dihydrogen citrate, alphaglyceryl phosphorylcholine, cytidine diphosphate-choline, choline folate, ester of choline with DHA, ester of choline with 3-methyl-2-hexenoic acid (MHA), ester of choline with medium chain triglyceride, other ester of choline with fatty acid, other salt of choline, or combinations thereof. In some additional aspects, the choline is present in an amount of about 50% to about 95% by weight based on the combined weight of the choline and coating formulation.

[0009] In some embodiments, the shellac has a concentration of about 1% to about 50% by weight, based on the combined weight of the at least one active ingredient and the coating formulation. In an exemplary embodiment, the coating formulation further comprises at least one of hydroxypropyl cellulose, silicon dioxide, starch, microcrystalline cellulose, ethyl cellulose, talc, and combinations thereof.

[0010] In some embodiments, the coating formulation further comprises a silicate. In some further embodiments, the silicate comprises silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or a combination thereof. In some examples, the silicate comprises silicon dioxide, and the silicon dioxide is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In yet further examples, the silicon dioxide is at least one of colloidal silicon dioxide or fumed silica.

[0011] In some embodiments, the coating formulation comprises a cellulose or derivative thereof. In some additional embodiments, the cellulose or derivative thereof comprises microcrystalline cellulose, powdered cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hypromellose, carboxymethyl cellulose, or a combination thereof.

[0012] In some embodiments, the coating formulation further comprises hydroxypropyl cellulose, hi some additional embodiments, the hydroxypropyl cellulose is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0013] In some embodiments, the coating formulation further comprises microcrystalline cellulose. In some additional embodiments, the microcrystalline cellulose is present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and the first and second active ingredients.

[0014] In some embodiments, the coating formulation further comprises ethyl cellulose, hi some additional embodiments, the ethyl cellulose is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the first active ingredient or the second active ingredient.

[0015] In some embodiments, the coating formulation further comprises a starch. In some further embodiments, the starch comprises corn starch, potato starch, rice starch, wheat starch, tapioca starch, or a combination thereof. In some additional embodiments, the starch is present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and the first active ingredient or the second active ingredient.

[0016] Further provided herein is a multi-component dosage form, the dosage form comprising at least one active ingredient and a coating formulation comprising shellac, the coating formulation coating the at least one active ingredient. In some embodiments, the shellac is present in an amount of about 1% to about 50% by weight, based on the total weight of the at least one active ingredient and the coating formulation. In some additional embodiments, the at least one active ingredient has a concentration of about 50.0% to about 95.0% by weight, based on the combined weight of the at least one active ingredient and the coating formulation.

[0017] In some embodiments, the at least one active ingredient comprises Vitamin C. In some aspects, 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. In some additional aspects, the Vitamin C is present in the dosage form in an amount of about 1 mg to about 2000 mg.

[0018] In some embodiments, the at least one active ingredient comprises choline. In some embodiments, the choline is selected from the group consisting of choline chloride, choline bitartrate, phosphatidylcholine, choline dihydrogen citrate, alphaglycerylphosphorylcholine, cytidine diphosphate-choline, choline folate, esters 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. In some additional aspects, the choline is present in the dosage form in an amount of about 1 mg to about 2000 mg.

[0019] In some exemplary embodiments, the coating formulation further comprises a silicate, a starch, a cellulose, or derivatives thereof, or a combination thereof.

[0020] In an exemplary embodiment, the at least one active ingredient comprises vitamin C and choline, and both vitamin C and choline are coated with a coating formulation. In another exemplary embodiment, the at least one active ingredient comprises choline, the dosage form further comprises vitamin C, and the vitamin C is not coated with a coating formulation. In yet another exemplary embodiment, the at least one active ingredient comprises vitamin C, the dosage form further comprises choline, and the choline is not coated with a coating formulation.

[0021] In some embodiments, the multi-component dosage form is a tablet, capsule, gummy, beverage, bar, suspension, granule, powder, lozenge, troche, granule, pill, gelcap, In some embodiments, the dosage form further comprises at least one of a vitamin, a mineral, a supplement, and an excipient.

[0022] In some embodiments, the multi-component dosage form exhibits little to no spotting after about 18 days, 30 days, or 60 days of storage at 25° C. and 20% relative humidity. In some embodiments, the multi-component dosage form exhibits little to no spotting after about 18 days, 30 days, or 60 days of storage at 25° C. and 30% relative humidity. In some embodiments, the multi-component dosage form exhibits little to no spotting after about 18 days, 30 days, or 60 days of storage at 45° C. and 20% relative humidity. In some embodiments, the multi-component dosage form exhibits little to no spotting after about 18 days, 30 days, or 60 days of storage at 45° C. and 30% relative humidity.

[0023] Further provided herein is 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 with a coating formulation comprising shellac, and including the active ingredient coated with the coating formulation in a dosage form. [Brief description of the drawings]

[0024] [Figure 1] 1 shows spotting for tablets of Example 1 containing vitamin C but no choline under different storage conditions. [Figure 2A] 4 different commercial tablets stored under different conditions are shown. [Figure 2B] 4 different commercial tablets stored under different conditions are shown. [Figure 2C] 4 different commercial tablets stored under different conditions are shown. [Figure 2D]4 different commercial tablets stored under different conditions are shown. [Diagram 3] 1 shows spotting for tablets 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 the relative humidity ranged from 0% RH to 60% RH. [Figure 4] 1 shows spotting for tablets of Example 1 containing choline and vitamin C under refrigerated storage conditions (4° C.) of 0% RH, 30% RH, and 60% RH for 18 days. [Figure 5A] 1 shows spotting under different storage conditions for tablets of Example 1 containing various forms of choline and vitamin C. [Figure 5B] 1 shows spotting under different storage conditions for tablets of Example 1 containing various forms of choline and vitamin C. [Figure 6A] 1 shows spotting under different storage conditions for tablets of Example 1 containing various dosage forms, different forms of vitamin C, and choline. [Figure 6B] 1 shows spotting under different storage conditions for tablets of Example 1 containing various dosage forms, different forms of vitamin C, and choline. [Figure 7] 1 shows spotting under different storage conditions for tablets of Example 1 containing vitamin C, choline, and a coating formulation of the present disclosure containing talc. [Figure 8] 1 shows the progression of spotting under different storage conditions for tablets of Example 1 containing vitamin C, choline, and a coating formulation of the present disclosure containing talc. [Figure 9] 1 shows the progression of spotting under different storage conditions for tablets containing vitamin C, choline, and a coating formulation of the present disclosure consisting of shellac. [Figure 10]1 shows the progression of spotting for tablets of Example 1 under different storage conditions, the tablets containing either a coating formulation of the present disclosure consisting of vitamin C, choline, and shellac, or no coating formulation. [Figure 11] 1 shows the progression of spotting for tablets of Example 1 under different storage conditions, the tablets containing a coating formulation of the present disclosure coated on choline, vitamin C, or both. [Figure 12A] FIG. 1 shows colorimeter diagrams for various tablets with various coating formulations of the present disclosure. [Figure 12B] FIG. 1 shows colorimeter diagrams for various tablets with various coating formulations of the present disclosure. [Figure 12C] FIG. 1 shows colorimeter diagrams for various tablets with various coating formulations of the present disclosure. [Figure 12D] FIG. 1 shows colorimeter diagrams for various tablets with various coating formulations of the present disclosure. [Figure 12E] FIG. 1 shows colorimeter diagrams for various tablets with various coating formulations of the present disclosure. [Figure 12F] FIG. 1 shows colorimeter diagrams for various tablets with various coating formulations of the present disclosure. [Figure 12G] FIG. 1 shows colorimeter diagrams for various tablets with various coating formulations of the present disclosure. [Figure 13] 1 shows tablets and ΔE values ​​for various tablets containing various coating formulations of the present disclosure. [Figure 14A] FIG. 1 shows colorimeter diagrams for various tablets that do not contain the coating formulation of the present disclosure. [Figure 14B] FIG. 1 shows colorimeter diagrams for various tablets that do not contain the coating formulation of the present disclosure. [Figure 14C] 1 shows exemplary samples used in the colorimeter experiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] It is to be understood that the present disclosure is not limited to the particular methods, compositions, or materials specified herein, but extends to equivalents thereof that would be recognized by one of ordinary skill in the relevant art. It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only, and is not intended to be limiting.

[0026] In this specification, concentrations, amounts, and other numerical data may be expressed or presented in a range format. It should also be understood that such range formats are used merely for convenience and brevity, and should be interpreted flexibly to include not only the numerical values ​​explicitly recited as range limits, but also all individual numerical values ​​or subranges subsumed within the range, as if each numerical value and subrange were explicitly recited. By way of illustration, the numerical range "about 2 to about 50" should be interpreted to include not only the values ​​2 to 50 explicitly recited, but also all individual values ​​and subranges within the indicated range. Thus, included in this numerical range are individual values ​​such as 2, 2.4, 3, 3.7, 4, 5.5, 10, 10.1, 14, 15, 15.98, 20, 20.13, 23, 25.06, 30, 35.1, 38.0, 40, 44, 44.6, 45, 48, and subranges such as, for example, 1-3, 2-4, 5-10, 5-20, 5-25, 5-30, 5-35, 5-40, 5-50, 2-10, 2-20, 2-30, 2-40, 2-50, etc. This same principle applies to ranges which state only one numerical value as a minimum or maximum value. Moreover, such an interpretation should be applied regardless of the breadth of the range or the characteristics being described.

[0027] As used herein, the term "about" is used to provide flexibility to the endpoints of a numerical range by providing the possibility that a given value may be "a little above" or "a little below" the endpoint. For example, the endpoints may be within 10%, 8%, 5%, 3%, 2%, or 1% of the stated value. Furthermore, for convenience and brevity, a numerical range of "about 50 mg / mL to about 80 mg / mL" is understood to also support the range "50 mg / mL to 80 mg / mL". Endpoints may be based on variability permitted by appropriate regulatory agencies such as the FDA, USP, etc. As used herein, "comprises", "comprising", "containing", and "having", etc. may have the meanings ascribed to them in U.S. Patent Law and may mean "includes", "including", etc., and are generally interpreted as open-ended terms. The terms "consisting of" or "consists of" are closed terms and include only those components, structures, steps, etc. specifically recited with such terms, as well as those pursuant to U.S. Patent Law. "Consisting essentially of" or "consists essentially of" have the meaning generally ascribed to them in U.S. Patent Law. Specifically, such terms are generally closed terms, with exceptions that permit the inclusion of additional items, materials, ingredients, steps, or elements that do not materially affect the basic and novel properties or function of the item(s) used in connection therewith. For example, trace elements that are present in the composition but do not affect the nature or properties of the composition would be permitted under the language "consisting essentially of" if present, even if they are not explicitly recited in the list of items following such terms.It is understood that where open-ended terminology such as "comprising" or "including" is used in this specification, direct support should be given to the words "consisting essentially of" as well as "consisting of," and vice versa, as if expressly stated.

[0028] As used herein, the term "spotting" refers to the formation of dark spots on dosage forms containing vitamin C and, optionally, choline chloride.

[0029] As used herein, the term "choline" refers to both the N,N,N-trimethylethanolammonium cation, as well as various quaternary 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. Thus, the term "choline" can be used interchangeably with "choline salts", "phospholipid-bound forms of choline", "esters of choline with fatty acids", and the like. However, when the term "choline salts" is used, this specifically refers to the salt form of the N,N,N-trimethylethanolammonium cation, when the term "esters of choline with medium-chain triglycerides" is used, this specifically refers to the esterified form of the N,N,N-trimethylethanolammonium cation, and so forth.

[0030] As used herein, the term "vitamin C" has the molecular formula C6H7O6 - Ascorbate ion refers to the ascorbate ion having the formula: ##STR00001## and both the acid, salt, and oxidized forms of the ascorbate ion. Thus, the term "vitamin C" may be used interchangeably with "ascorbic acid." When amounts or concentrations of vitamin C are mentioned herein, they generally refer to the concentration or amount of the ascorbate ion, for example, the phrase "vitamin C may be present in an amount of 1 mg" generally means herein that the amount of ascorbate ion is 1 mg.

[0031] As used herein, the term "shellac" refers to the resin secreted by female lac scale insects. The term encompasses raw shellac, liquid shellac, and shellac that has been processed, modified, or purified by methods known to those skilled in the art, particularly by methods known to prepare shellac for pharmaceutical use. Additionally, the term includes derivatives or analogs of shellac.

[0032] Disclosed herein is a coating formulation that is useful for preventing spotting in a multi-component dosage form containing vitamin C and, optionally, choline chloride. The coating formulation comprises shellac. Without being bound by theory, the coating formulation may reduce the rate of decomposition of vitamin C by protecting vitamin C from moisture and reducing contact with other components (e.g., metals and metal oxides) in the multi-component dosage form. Additionally or alternatively, and without being bound by theory, the coating formulation may prevent choline chloride from absorbing excess moisture from the environment or from other components in the dosage form, which may accelerate the decomposition of vitamin C. This may also have the added benefit of reducing the formation of metal oxides and reducing interactions with metals in the multi-component dosage form. Furthermore, the coating formulation is resistant to crushing when compressed, allowing the coating formulation to be used in tablets and other dosage forms produced by compression.

[0033] I. Composition A. Coating formulation Disclosed herein is a coating formulation that is useful for preventing spotting in a dosage form that contains at least one active ingredient. The coating formulation comprises shellac. In some examples, the coating formulation can consist of shellac or consist essentially of shellac. The coating formulation surrounds the active ingredient. The coating formulation can completely surround the active ingredient or can substantially surround the active ingredient (i.e., 95% or more of the active ingredient). Preferably, the coating formulation does not coat the entire dosage form, but only coats the active ingredient described below.

[0034] The particle size of the coated active ingredient (i.e., the coating formulation plus the active ingredient) can be about 1 micron to about 2000 microns. In some embodiments, the particle size of the coated active ingredient can be 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. In some additional embodiments, the particle size of the coated active ingredient may be 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. In still further embodiments, 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.

[0035] The coating formulation may be present in an amount of about 5% to about 50% by weight, based on the combined weight of the at least one active ingredient and the coating formulation. In some embodiments, the coating formulation may be present in an amount of about 5% to about 10% by weight, about 5% to about 15% by weight, about 5% to about 20% by weight, about 5% to about 25% by weight, about 5% to about 30% by weight, about 5% to about 35% by weight, about 5% to about 40% by weight, about 5% to about 45% by weight, about 45% to about 50% by weight, about 40% to about 50% by weight, about 35% to about 50% by weight, about 30% to about 50% by weight, about 25% to about 50% by weight, about 15% to about 50% by weight, or about 10% to about 50% by weight, based on the combined weight of the at least one active ingredient and the coating formulation. In some additional embodiments, the coating formulation may be present in an amount of about 5%, 7.5%, 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, 30%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%, 47.5%, or about 50% by weight, based on the combined weight of the at least one active ingredient and the coating formulation.

[0036] The shellac may be present in the coating formulation in an amount of about 1% to about 50% by weight, based on the combined weight of the at least one active ingredient and the coating formulation. In some embodiments, the shellac may be present in an amount of about 1% to about 5% by weight, about 1% to about 10% by weight, about 1% to about 15% by weight, about 1% to about 20% by weight, about 1% to about 25% by weight, about 1% to about 30% by weight, about 1% to about 35% by weight, about 1% to about 40% by weight, about 1% to about 45% by weight, about 45% to about 50% by weight, about 40% 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 mass% to about 50 mass%, about 5 mass% to about It may be present in an amount of 50% by weight, about 5% to about 40% by weight, about 5% to about 30% by weight, about 5% to about 20% by weight, about 10% to about 40% by weight, about 10% to about 30% by weight, or about 10% to about 20% by weight. In some additional embodiments, the shellac may be present in an amount of about 1%, 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, 30%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%, 47.5%, or about 50% by weight based on the combined weight of the at least one active ingredient and the coating formulation. In some examples, the shellac may be present in an amount of about 5% to about 20% by weight based on the combined weight of the at least one active ingredient and the coating formulation.

[0037] The coating formulation may include silicates 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 silicates act as adsorbents, anti-caking agents, glidants, disintegrants, and the like. The silicon dioxide may include colloidal silicon dioxide, fumed (pyrogenated) silica, or other forms of silicon dioxide. The silicates may be present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some embodiments, the silicate may be present in the coating formulation in an amount of about 0% to about 2% by weight, 0% to about 3% by weight, about 0% to about 4% by weight, about 0% to about 5% by weight, about 0% to about 6% by weight, about 0% to about 7% by weight, 0% to about 8% by weight, about 0% to about 9% by weight, about 1% to about 10% by weight, about 2% to about 10% by weight, about 3% to about 10% by weight, about 4% to about 10% by weight, about 5% to about 10% by weight, about 6% to about 10% by weight, about 7% to about 10% by weight, about 8% to about 10% by weight, about 0.5% to about 5% by weight, or about 1% to about 3% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some additional embodiments, the silicate may be present in the coating formulation in an amount of about 0% to about 1%, about 1% to about 2%, about 2% to about 3%, about 3% to about 4%, about 4% to about 5%, about 5% to about 6%, about 6% to about 7%, about 7% to about 8%, about 8% to about 9%, or about 9% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In still further embodiments, the silicate may be present in the coating formulation in an amount of about 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.In an exemplary embodiment, the silicate is present in the coating formulation in an amount of about 0.5% to about 3% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In another exemplary embodiment, the silicate is colloidal silicon dioxide.

[0038] The coating formulation may include starch, such as corn starch, potato starch, rice starch, wheat starch, tapioca starch, and other starches, or combinations thereof. The starch acts as a lubricant and a low-solubility coating. The starch may be present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some embodiments, the starch may be present in the coating formulation in an amount of about 0% to about 5% by weight, about 5% to about 10% by weight, about 10% to about 15% by weight, about 15% to about 20% by weight, or about 20% to about 25% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some additional embodiments, the starch may be present in the coating formulation in an amount of about 0% to about 10% by weight, about 0% to about 15% by weight, about 0% to about 20% by weight, about 5% to about 25% by weight, about 10% to about 25% by weight, about 15% to about 25% by weight, or about 5% to about 20% by weight. In still further aspects, the starch may be present in the coating formulation in an amount of about 0%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or about 25% by weight based on the combined weight of the coating formulation and the at least one active ingredient. In an exemplary embodiment, the starch is present in the coating formulation in an amount of about 9% to about 16% by weight based on the combined weight of the coating formulation and the at least one active ingredient.

[0039] The coating formulation may include cellulose or its derivatives, such as microcrystalline cellulose, powdered cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hypromellose (e.g., hypromellose acetate succinate), carboxymethyl cellulose (e.g., sodium carboxymethyl cellulose), and combinations thereof. In some aspects, the cellulose may be blended with other ingredients, such as carrageenan, phosphates (e.g., calcium phosphate), gums (e.g., guar gum), mannitol, silicates, and the like.

[0040] In some embodiments, the coating formulation may include microcrystalline cellulose. Microcrystalline cellulose acts as an adsorbent, compression aid, diluent, binder, and disintegrant in the dosage forms described herein. The microcrystalline cellulose may be present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and at least one active ingredient. In some aspects, the microcrystalline cellulose may be present in an amount of about 0% to about 5% by weight, about 5% to about 10% by weight, about 10% to about 15% by weight, about 15% to about 20% by weight, or about 20% to about 25% by weight, based on the combined weight of the coating formulation and at least one active ingredient. In some additional embodiments, the microcrystalline cellulose may be present in the coating formulation in an amount of about 0% to about 10% by weight, about 0% to about 15% by weight, about 0% to about 20% by weight, about 5% to about 25% by weight, about 10% to about 25% by weight, about 15% to about 25% by weight, or about 5% to about 20% by weight. In yet further aspects, microcrystalline cellulose can be present in an amount of about 0% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 21% by weight, 22% by weight, 23% by weight, 24% by weight, or about 25% by weight based on the combined weight of the coating formulation and the at least one active ingredient.In an exemplary embodiment, microcrystalline cellulose is present in an amount of about 9% to about 12% by weight based on the combined weight of the coating formulation and the at least one active ingredient.

[0041] In some embodiments, the coating formulation may include hydroxypropyl cellulose. Hydroxypropyl cellulose adds flexibility to the coating. Hydroxypropyl cellulose may be present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some embodiments, hydroxypropylcellulose may be present in the coating formulation in an amount of about 0% to about 2% by weight, 0% to about 3% by weight, about 0% to about 4% by weight, about 0% to about 5% by weight, about 0% to about 6% by weight, about 0% to about 7% by weight, 0% to about 8% by weight, about 0% to about 9% by weight, about 1% to about 10% by weight, about 2% to about 10% by weight, about 3% to about 10% by weight, about 4% to about 10% by weight, about 5% to about 10% by weight, about 6% to about 10% by weight, about 7% to about 10% by weight, about 8% to about 10% by weight, about 0.5% to about 5% by weight, or about 1% to about 3% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some additional embodiments, the hydroxypropyl cellulose may be present in the coating formulation in an amount of about 0% to about 1%, about 1% to about 2%, about 2% to about 3%, about 3% to about 4%, about 4% to about 5%, about 5% to about 6%, about 6% to about 7%, about 7% to about 8%, about 8% to about 9%, or about 9% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In still further embodiments, the hydroxypropyl cellulose may be present in the coating formulation in an amount of about 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In an exemplary embodiment, hydroxypropyl cellulose is present in the coating formulation in an amount of about 0.25% to about 1.5% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0042] In some embodiments, the coating formulation may include hydroxypropyl methylcellulose, which adds flexibility to the coating. Hydroxypropyl methylcellulose may be present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some embodiments, hydroxypropyl methylcellulose may be present in the coating formulation in an amount of about 0% to about 2% by weight, 0% to about 3% by weight, about 0% to about 4% by weight, about 0% to about 5% by weight, about 0% to about 6% by weight, about 0% to about 7% by weight, 0% to about 8% by weight, about 0% to about 9% by weight, about 1% to about 10% by weight, about 2% to about 10% by weight, about 3% to about 10% by weight, about 4% to about 10% by weight, about 5% to about 10% by weight, about 6% to about 10% by weight, about 7% to about 10% by weight, about 8% to about 10% by weight, about 0.5% to about 5% by weight, or about 1% to about 3% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some additional embodiments, hydroxypropyl methylcellulose may be present in the coating formulation in an amount of about 0% to about 1%, about 1% to about 2%, about 2% to about 3%, about 3% to about 4%, about 4% to about 5%, about 5% to about 6%, about 6% to about 7%, about 7% to about 8%, about 8% to about 9%, or about 9% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In still further embodiments, hydroxypropyl methylcellulose may be present in the coating formulation in an amount of about 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0043] In some embodiments, the coating formulation may further include ethylcellulose, which may be present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some embodiments, ethylcellulose may be present in the coating formulation in an amount of about 0% to about 2% by weight, 0% to about 3% by weight, about 0% to about 4% by weight, about 0% to about 5% by weight, about 0% to about 6% by weight, about 0% to about 7% by weight, 0% to about 8% by weight, about 0% to about 9% by weight, about 1% to about 10% by weight, about 2% to about 10% by weight, about 3% to about 10% by weight, about 4% to about 10% by weight, about 5% to about 10% by weight, about 6% to about 10% by weight, about 7% to about 10% by weight, about 8% to about 10% by weight, about 0.5% to about 5% by weight, or about 1% to about 3% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In some additional embodiments, ethylcellulose may be present in the coating formulation in an amount of about 0% to about 1%, about 1% to about 2%, about 2% to about 3%, about 3% to about 4%, about 4% to about 5%, about 5% to about 6%, about 6% to about 7%, about 7% to about 8%, about 8% to about 9%, or about 9% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In still further embodiments, ethylcellulose may be present in the coating formulation in an amount of about 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient. In an exemplary embodiment, the ethylcellulose is present in the coating formulation in an amount of about 0.1% to about 1% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0044] The coating formulation may further include one or more excipients. The one or more excipients may include sugars (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, flavorings, lubricants, binders, fillers, glidants, diluents, adsorbents, disintegrants, film-forming agents, compression aids, and other excipients known to those skilled in the art.

[0045] B. Active ingredients The coating formulation coats at least one active ingredient contained within the multi-component dosage form.

[0046] At least one active ingredient may include vitamin C and choline. In some exemplary embodiments, at least one active ingredient may include only vitamin C, only choline, or both vitamin C and choline. In some additional exemplary embodiments, the multi-component 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. In yet other exemplary embodiments, the multi-component dosage form may contain vitamin C and choline, both of which are coated with the coating formulation of the present disclosure, but the composition of the coating formulation for vitamin C is different from the composition of the coating formulation for choline. In yet other exemplary embodiments, the multi-component dosage form may contain both vitamin C and choline, both of which are coated with the coating formulation of the same composition.

[0047] The at least one active ingredient may include a fat soluble vitamin or a derivative thereof, such as vitamin A, vitamin D, vitamin E, vitamin K, and other fat soluble vitamins and derivatives thereof known in the art.

[0048] The at least one active ingredient may include water soluble vitamins or derivatives thereof, such as folic acid, thiamine, riboflavin, niacin, biotin, pantothenic acid, pyridoxine, cobalamin, and other water soluble vitamins and derivatives thereof known in the art.

[0049] 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, as well as salts, complexes, or chelates thereof.

[0050] The at least one active ingredient may comprise a drug or pharmaceutical agent such as analgesics, anti-inflammatory agents, antiarrhythmic agents, antiasthmatic agents, antibacterial agents, antiviral agents, anticoagulants, antidepressants, antidiabetic agents, antiepileptic agents, antifungal agents, antihypertensive agents, antimalarial agents, antimigraine agents, antimuscarinic agents, antitumor agents, immunosuppressants, antiprotozoal agents, antithyroid agents, anxiolytic agents, sedatives, hypnotics, neuroleptic agents, beta-blockers, cardiac inotropes, corticosteroids, diuretics, antiparkinsonian agents, gastrointestinal agents, antihistamines, histamine receptor antagonists, lipid regulating agents, muscle relaxants, nitrates and other antianginal agents, nutritional agents, opioid analgesics, or stimulants.

[0051] Vitamin C At least one active ingredient may include vitamin C. 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 form of vitamin C known in the art, or combinations thereof. In some examples, vitamin C is ascorbic acid.

[0052] In some embodiments, vitamin C may be present in an amount of about 50% to about 95% by weight based on the combined weight of vitamin C and the coating formulation. In some aspects, vitamin C may be present in an amount of about 50% to about 55% by weight, about 55% to about 60% by weight, about 60% to about 65% by weight, about 65% to about 70% by weight, about 70% to about 75% by weight, about 75% to about 80% by weight, about 80% to about 85% by weight, about 85% to about 90% by weight, or about 90% to about 95% by weight based on the combined weight of vitamin C and the coating formulation. In some additional embodiments, vitamin C may be present in an amount of about 50% to about 60% by weight, about 50% to about 65% by weight, about 50% to about 70% by weight, about 50% to about 75% by weight, about 50% to about 80% by weight, about 50% to about 85% by weight, about 50% to about 90% by weight, about 55% to about 95% by weight, about 60% to about 95% by weight, about 65% to about 95% by weight, about 70% to about 95% by weight, about 75% to about 95% by weight, about 80% to about 95% by weight, or about 85% to about 95% by weight, based on the combined weight of vitamin C and the coating formulation. In still further aspects, vitamin C may be present in an amount of about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or about 95% by weight based on the combined weight of vitamin C and the coating formulation. In some exemplary embodiments, vitamin C may be present in an amount of about 70% to about 80% by weight based on the combined weight of vitamin C and the coating formulation.

[0053] ii. Choline In some embodiments, at least one active ingredient may comprise choline.Choline may comprise choline chloride, choline bitartrate, phosphatidylcholine, choline dihydrogen citrate, alphaglyceryl phosphorylcholine, cytidine diphosphate-choline, choline folate, choline ester with DHA, choline ester with 3-methyl-2-hexenoic acid (MHA), choline ester with medium chain triglyceride, other esters of choline with fatty acid, other salts of choline, or combinations thereof.In some examples, choline is choline bitartrate.

[0054] In some embodiments, the choline may be present in an amount of about 50% to about 95% by weight based on the combined weight of the coating formulation and the choline. In some aspects, the choline may be present in an amount of about 50% to about 55% by weight, about 55% to about 60% by weight, about 60% to about 65% by weight, about 65% to about 70% by weight, about 70% to about 75% by weight, about 75% to about 80% by weight, about 80% to about 85% by weight, about 85% to about 90% by weight, or about 90% to about 95% by weight based on the combined weight of the coating formulation and the choline. In some additional embodiments, the choline may be present in an amount of about 50% to about 60% by weight, about 50% to about 65% by weight, about 50% to about 70% by weight, about 50% to about 75% by weight, about 50% to about 80% by weight, about 50% to about 85% by weight, about 50% to about 90% by weight, about 55% to about 95% by weight, about 60% to about 95% by weight, about 65% to about 95% by weight, about 70% to about 95% by weight, about 75% to about 95% by weight, about 80% to about 95% by weight, or about 85% to about 95% by weight, based on the combined weight of the vitamin C and the coating formulation. In still further aspects, the choline may be present in an amount of about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or about 95% by weight based on the combined weight of the vitamin C and the coating formulation. In some exemplary embodiments, the choline may be present in an amount of about 75% to about 85% by weight based on the combined weight of the choline and the coating formulation.

[0055] C. Dosage form Further described herein is a multi-component dosage form comprising the 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 ingredient described in section IB above, but the coating formulation preferably does not coat the entire dosage form.The multi-component dosage form comprises additional components, including vitamins, minerals, nutrients, supplements, drugs, excipients, fillers, binders, lubricants, plasticizers, etc.

[0056] In some embodiments, the multi-component dosage form can be a tablet, capsule, gummy, beverage, bar, suspension, granule, powder, lozenge, pastille, granule, pill, gelcap, or other dosage form known in the art. In the example where the dosage form is a tablet, the coating formulation can resist crushing when the components are compressed into the tablet.

[0057] Multicomponent dosage forms can be modified to have a desired release profile, in some embodiments, the dosage form can be immediate release, controlled release, extended release, modified release, or sustained release.

[0058] The multi-component dosage form comprises the coating formulation of the present disclosure (see Section IA of the detailed description of the present invention). The coating formulation comprises shellac. The coating formulation coats at least one active ingredient in the multi-component dosage form (see Section IB of the detailed description of the present invention).

[0059] At least one active ingredient may include vitamin C. 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 form of vitamin C known in the art, or combinations thereof. In some examples, vitamin C is ascorbic acid.

[0060] In some embodiments, vitamin C may be present in an amount of about 50% to about 95% by weight based on the combined weight of vitamin C and the coating formulation. In some aspects, vitamin C may be present in an amount of about 50% to about 55% by weight, about 55% to about 60% by weight, about 60% to about 65% by weight, about 65% to about 70% by weight, about 70% to about 75% by weight, about 75% to about 80% by weight, about 80% to about 85% by weight, about 85% to about 90% by weight, or about 90% to about 95% by weight based on the combined weight of vitamin C and the coating formulation. In some additional embodiments, vitamin C may be present in an amount of about 50% to about 60% by weight, about 50% to about 65% by weight, about 50% to about 70% by weight, about 50% to about 75% by weight, about 50% to about 80% by weight, about 50% to about 85% by weight, about 50% to about 90% by weight, about 55% to about 95% by weight, about 60% to about 95% by weight, about 65% to about 95% by weight, about 70% to about 95% by weight, about 75% to about 95% by weight, about 80% to about 95% by weight, or about 85% to about 95% by weight, based on the combined weight of vitamin C and the coating formulation. In still further aspects, vitamin C may be present in an amount of about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or about 95% by weight based on the combined weight of vitamin C and the coating formulation. In some exemplary embodiments, vitamin C may be present in an amount of about 70% to about 80% by weight based on the combined weight of vitamin C and the coating formulation.

[0061] In some embodiments, vitamin C may be present in the multi-component dosage form in an amount of about 1 mg to about 2000 mg. In some aspects, vitamin C may be present in the multi-component dosage form in an amount of 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, or about 1750 mg to about 2000 mg. In some additional embodiments, vitamin C may be present in the multi-component dosage form in an amount of 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. In still further embodiments, vitamin C may be present in the multi-component 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.

[0062] At least one active ingredient may comprise choline.Choline may comprise choline chloride, choline bitartrate, phosphatidylcholine, choline dihydrogen citrate, alphaglyceryl phosphorylcholine, cytidine diphosphate-choline, choline folate, choline ester with DHA, choline ester with 3-methyl-2-hexenoic acid (MHA), choline ester with medium chain triglyceride, other esters of choline with fatty acid, other salts of choline, or any other form of choline known in the art, or combinations thereof.In some exemplary embodiments, choline is choline bitartrate.

[0063] The choline may be present in an amount of about 50% to about 95% by weight based on the combined weight of the coating formulation and the choline. In some embodiments, the choline may be present in an amount of about 50% to about 55% by weight, about 55% to about 60% by weight, about 60% to about 65% by weight, about 65% to about 70% by weight, about 70% to about 75% by weight, about 75% to about 80% by weight, about 80% to about 85% by weight, about 85% to about 90% by weight, or about 90% to about 95% by weight based on the combined weight of the coating formulation and the choline. In some additional embodiments, the choline may be present in an amount of about 50% to about 60% by weight, about 50% to about 65% by weight, about 50% to about 70% by weight, about 50% to about 75% by weight, about 50% to about 80% by weight, about 50% to about 85% by weight, about 50% to about 90% by weight, about 55% to about 95% by weight, about 60% to about 95% by weight, about 65% to about 95% by weight, about 70% to about 95% by weight, about 75% to about 95% by weight, about 80% to about 95% by weight, or about 85% to about 95% by weight, based on the combined weight of the vitamin C and the coating formulation. In still further aspects, the choline may be present in an amount of about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or about 95% by weight based on the combined weight of the vitamin C and the coating formulation. In some exemplary embodiments, the choline may be present in an amount of about 75% to about 85% by weight based on the combined weight of the choline and the coating formulation.

[0064] Choline may be present in the multi-component dosage form in an amount of about 1 mg to about 2000 mg. In some embodiments, choline may be present in the multi-component dosage form in an amount of 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, or about 1750 mg to about 2000 mg. In some additional embodiments, the choline may be present in the multi-component dosage form in an amount of 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. In still further embodiments, the choline may be present in the multi-component 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.

[0065] The multi-component dosage form may further include vitamins other than vitamin C. In some embodiments, the vitamins may include one or more of vitamin A (i.e., retinoids or carotenes), vitamin D (i.e., calciferol), vitamin E (i.e., alpha-tocopherol), vitamin K (i.e., phylloquinone or menadione), vitamin B1 (i.e., thiamine), 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 to those of skill in the art.

[0066] The multi-component dosage form may further comprise minerals, hi some embodiments, the minerals may include calcium, chloride, chromium, copper, fluoride, iodine, iron, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, sodium, sulfur, zinc, or other minerals known to those of skill in the art, or pharma- ceutically acceptable salts thereof.

[0067] The multi-component dosage form may further include a supplement. In some embodiments, 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 biloba, glucomannan, glucosamine, glutathione, gotu kola, hyaluronic acid, inositol, krill oil, licorice, lutein, maca, melatonin, moringa, omega fatty acids, prebiotics, probiotics, quercetin, rhodiola, saw palmetto, serrapeptase, taurine, turmeric, valerian, whey protein, xylitol, or other supplements known to one of skill in the art.

[0068] The multi-component dosage form may further comprise excipients, which may include binders, plasticizers, fillers, bulking agents, disintegrants, glidants, lubricants, diluents, flavorings, fragrances, flavor masking agents, aroma masking agents, anti-caking agents, preservatives, humectants, humectants, and other excipients known to those skilled in the art.

[0069] Multicomponent dosage forms may contain one or more additional active ingredients that are not coated with the coating formulations described herein.

[0070] The dosage forms of the present disclosure may exhibit 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 exhibit 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 colorimetric measurements, as described herein.

[0071] The dosage forms of the present disclosure may exhibit little or no spotting after about 18 days of storage at a temperature of 45° C. and a relative humidity of 20%. For example, the dosage forms may exhibit 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 colorimetric measurements, as described herein.

[0072] The dosage forms of the present disclosure may exhibit little or no spotting after about 18 days of storage at a temperature of 25° C. and a relative humidity of 30%. For example, the dosage forms may exhibit 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 colorimetric measurements, as described herein.

[0073] The dosage forms of the present disclosure may exhibit little or no spotting after about 18 days of storage at a temperature of 45° C. and a relative humidity of 30%. For example, the dosage forms may exhibit 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 colorimetric measurements, as described herein.

[0074] The multi-component dosage form may be suitable for administration to a subject. The subject may be a human, such as an adult or a child.

[0075] II. Method A. Methods for preventing spotting in dosage forms A method for preventing spotting in a dosage form containing vitamin C and / or choline is described herein. The method includes providing at least one active ingredient including at least one of vitamin C and choline, coating the at least one active ingredient with a coating formulation including shellac, and including the at least one active ingredient coated with the coating formulation in a dosage form. The coating formulation can be any of the coating formulations of the present disclosure described in Section I.

[0076] Coating at least one active ingredient with a coating formulation comprising shellac can be accomplished by pan coating, fluid bed coating, spray blending, or other coating methods known in the art.

[0077] The amount of spotting in the dosage form can be determined by visual determination or by colorimetric measurement. A colorimeter can be used to measure the amount of spotting in the dosage form by comparing the dosage form to a reference dosage form of the same composition. The color change can be measured by determining the total color difference (ΔE) of the dosage form compared to the reference dosage form, or by other methods known in the art, with a ΔE of 0 indicating no color change. In some embodiments, the average ΔE in the dosage form can be about 2.5 or less, or more preferably about 1.0 or less. For example, ΔE can 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 ΔE of less than 1.0 is generally considered a visually unnoticeable color change. As used herein, a dosage form having "almost no spotting" refers to a dosage form having a ΔE of 2.5 or less compared to a reference dosage form, and a dosage form having "no spotting" refers to a dosage form having a ΔE of 1.0 or less compared to a reference dosage form.

[0078] The dosage forms of the present disclosure may exhibit little or no spotting after about 18 days of storage at a temperature of 25° C. and a relative humidity of 20%. For example, the dosage forms may exhibit 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 colorimetric measurements, as described herein.

[0079] The dosage forms of the present disclosure may exhibit little or no spotting after about 18 days of storage at a temperature of 45° C. and a relative humidity of 20%. For example, the dosage forms may exhibit 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 colorimetric measurements, as described herein.

[0080] The dosage forms of the present disclosure may exhibit little or no spotting after about 18 days of storage at a temperature of 25° C. and a relative humidity of 30%. For example, the dosage forms may exhibit 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 colorimetric measurements, as described herein.

[0081] The dosage forms of the present disclosure may exhibit little or no spotting after about 18 days of storage at a temperature of 45° C. and a relative humidity of 30%. For example, the dosage forms may exhibit 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 colorimetric measurements, as described herein.

[0082] B. Methods of Making Coating Formulations and Dosage Forms The coating formulation of the present disclosure can be manufactured by methods known in the art. The coating formulation can be made by dissolving shellac and other coating formulation components described in Section I above in a suitable solvent, such as an alcohol solvent. In one embodiment, the solvent can be ethanol.

[0083] The active ingredient may then be provided in a particulate form (e.g., granules). The active ingredient may include choline or vitamin C, or any other active ingredient provided in Section I.

[0084] The coating formulation can then be applied to the active ingredient using coating methods known in the art, such as pan coating, spray coating, etc. When the solvent dries, the coating formulation is applied to the active ingredient, thus forming a coated composition. The coated composition can be sieved to adjust the average particle size of the coated composition.

[0085] The dosage form may be manufactured by various methods known to those skilled in the art. The dosage form may be a tablet, capsule, gummy, beverage, bar, suspension, granulation, powder, drop, lozenge, granule, pill, gelcap, or other solid dosage form known to those skilled in the art. In an exemplary embodiment, the dosage form is a tablet. The coated composition may be incorporated into the dosage form using methods known to those skilled in the art. For example, the coated composition may be combined with other ingredients and compressed to form a tablet. It will be understood that some unit operations may be modified or omitted to prevent damage to the coating formulation. For example, milling the dosage form may be omitted to prevent damage to the coating formulation.

[0086] C. Method of Administration Further provided herein is a method of administering the dosage form described in Section I. The method may include administering the dosage form of the present disclosure orally, sublingually, or bucally to a subject. The subject may be a human, such as an adult or a child. In some embodiments, the subject may have a nutritional deficiency or insufficiency, such as vitamin C deficiency, choline deficiency, or both. Thus, in some embodiments, the method may be suitable for supplementing nutrition to a subject.

[0087] Exemplary embodiments Embodiment 1: A coating formulation comprising shellac, wherein the coating formulation coats at least one active ingredient in a multi-component dosage form.

[0088] Embodiment 2: The coating formulation of embodiment 1, wherein the at least one active ingredient has a concentration of about 50.0% by weight to about 95.0% by weight, based on the total weight of the at least one active ingredient and the coating formulation.

[0089] Embodiment 3: The coating formulation of embodiment 1 or embodiment 2, wherein the at least one active ingredient comprises vitamin C.

[0090] 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.

[0091] Embodiment 5: The coating formulation of embodiment 3 or embodiment 4, wherein the vitamin C is present in an amount of about 50% to about 95% by weight, based on the combined weight of the vitamin C and the coating formulation.

[0092] Embodiment 6: The coating formulation of any one of embodiments 1 to 5, wherein the at least one active ingredient comprises choline.

[0093] Embodiment 7: The coating formulation of claim 6, wherein the choline is selected from the group consisting of choline chloride, choline bitartrate, phosphatidylcholine, choline dihydrogen citrate, alphaglycerylphosphorylcholine, cytidine diphosphate-choline, choline folate, esters 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.

[0094] Embodiment 8: The coating formulation of embodiment 6 or embodiment 7, wherein the choline is present in an amount of about 50% to about 95% by weight, based on the combined weight of the choline and the coating formulation.

[0095] Embodiment 9: The coating formulation of any one of embodiments 1 to 8, wherein the shellac is present in an amount of about 1% to about 50% by weight, based on the combined weight of the at least one active ingredient and the coating formulation.

[0096] Embodiment 10: The coating formulation of any one of embodiments 1 to 9, wherein the coating formulation further comprises a silicate.

[0097] Embodiment 11: The coating formulation of embodiment 10, wherein the silicate comprises silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or a combination thereof.

[0098] Embodiment 12: The coating formulation of embodiment 10 or embodiment 11, wherein the silicate is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0099] Embodiment 13: The coating formulation of embodiment 11, wherein the silicon dioxide comprises colloidal silicon dioxide or fumed silica.

[0100] Embodiment 14: The coating formulation of any one of embodiments 1 to 13, wherein the coating formulation further comprises cellulose or a derivative thereof.

[0101] Embodiment 15: The coating formulation of embodiment 14, wherein the cellulose or a derivative thereof comprises microcrystalline cellulose, powdered cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hypromellose, carboxymethyl cellulose, or a combination thereof.

[0102] Embodiment 16: The coating formulation of embodiment 14 or embodiment 15, wherein the cellulose or derivatives thereof comprises hydroxypropyl cellulose.

[0103] Embodiment 17: The coating formulation of embodiment 16, wherein the hydroxypropyl cellulose is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0104] Embodiment 18: The coating formulation of embodiment 14 or embodiment 15, wherein the cellulose or a derivative thereof comprises microcrystalline cellulose.

[0105] Embodiment 19: The coating formulation of embodiment 18, wherein the microcrystalline cellulose is present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and the first active ingredient and the second active ingredient.

[0106] Embodiment 20: The coating formulation of embodiment 14 or embodiment 15, wherein the cellulose or a derivative thereof comprises ethyl cellulose.

[0107] Embodiment 21: The coating formulation of embodiment 20, wherein the ethylcellulose is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the first active ingredient or the second active ingredient.

[0108] Embodiment 22: The coating formulation of any one of embodiments 1 to 21, wherein the coating formulation further comprises starch.

[0109] Embodiment 23: The coating formulation of embodiment 22, wherein the starch comprises corn starch, potato starch, rice starch, wheat starch, tapioca starch, or a combination thereof.

[0110] Embodiment 24: The coating formulation of embodiment 22 or embodiment 23, wherein the starch is present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and the first active ingredient or the second active ingredient.

[0111] Embodiment 25: A multicomponent dosage form, the dosage form comprising at least one active ingredient and a coating formulation comprising shellac, the coating formulation coating the at least one active ingredient.

[0112] Embodiment 26: The dosage form of embodiment 25, wherein the at least one active ingredient comprises vitamin C.

[0113] Embodiment 27: The dosage form of embodiment 26, wherein vitamin C is present in the dosage form in an amount from about 1 mg to about 2000 mg.

[0114] Embodiment 28: The dosage form of embodiment 26 or embodiment 27, 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.

[0115] Embodiment 29: A dosage form according to any one of embodiments 25 to 28, wherein the at least one active ingredient comprises choline.

[0116] Embodiment 30: The dosage form of embodiment 29, wherein the choline is present in the dosage form in an amount of from about 1 mg to about 2000 mg.

[0117] Embodiment 31: The dosage form of embodiment 29 or embodiment 30, wherein the choline is selected from the group consisting of choline chloride, choline bitartrate, phosphatidylcholine, choline dihydrogen citrate, alphaglycerylphosphorylcholine, cytidine diphosphate-choline, choline folate, esters 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.

[0118] Embodiment 32: A dosage form described in any one of embodiments 25 to 31, wherein the shellac is present in an amount of about 1% by weight to about 50% by weight, based on the total weight of the at least one active ingredient and the coating formulation.

[0119] Embodiment 33: The dosage form of any one of embodiments 25 to 32, wherein the at least one active ingredient is present in an amount of about 50.0% by weight to about 95.0% by weight, based on the combined weight of the at least one active ingredient and the coating formulation.

[0120] Embodiment 34: The dosage form of any one of embodiments 25 to 33, wherein the at least one active ingredient comprises vitamin C and choline, and the choline is not coated with a coating formulation.

[0121] 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 with a coating formulation.

[0122] 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 with a coating formulation.

[0123] Embodiment 37: The dosage form of any one of embodiments 25 to 36, wherein the dosage form is a tablet, capsule, gummy, beverage, bar, suspension, granulation, powder, drop, troche, granule, pill, or gelcap.

[0124] Embodiment 38: The dosage form of any one of embodiments 25 to 37, wherein the dosage form further comprises at least one of vitamins, minerals, supplements, and excipients.

[0125] Embodiment 39: The dosage form of any one of embodiments 25 to 38, wherein the dosage form further comprises an additional active ingredient that is not coated by the coating formulation.

[0126] Embodiment 40: A dosage form described in any one of embodiments 25 to 39, wherein the coating formulation further comprises a silicate.

[0127] Embodiment 41: The dosage form of embodiment 40, wherein the silicate comprises silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or a combination thereof.

[0128] Embodiment 42: The dosage form of embodiment 40 or embodiment 41, wherein the silicate is present in the coating formulation in an amount of about 0% by weight to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0129] Embodiment 43: A dosage form of embodiment 41, wherein the silicon dioxide comprises colloidal silicon dioxide or fumed silica.

[0130] Embodiment 44: A dosage form described in any one of embodiments 25 to 43, wherein the coating formulation further comprises cellulose or a derivative thereof.

[0131] Embodiment 45: The dosage form of embodiment 44, wherein the cellulose or a derivative thereof comprises microcrystalline cellulose, powdered cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hypromellose, carboxymethyl cellulose, or a combination thereof.

[0132] Embodiment 46: The dosage form of embodiment 44 or embodiment 45, wherein the cellulose or derivative thereof comprises hydroxypropyl cellulose.

[0133] Embodiment 47: The dosage form of embodiment 46, wherein the hydroxypropyl cellulose is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0134] Embodiment 48: A dosage form according to embodiment 44 or embodiment 45, wherein the cellulose or derivative thereof comprises microcrystalline cellulose.

[0135] Embodiment 49: The dosage form of embodiment 48, wherein the microcrystalline cellulose is present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and the first active ingredient and the second active ingredient.

[0136] Embodiment 50: The dosage form of embodiment 44 or embodiment 45, wherein the cellulose or derivative thereof comprises ethylcellulose.

[0137] Embodiment 51: The dosage form of embodiment 50, wherein the ethylcellulose is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the first active ingredient or the second active ingredient.

[0138] Embodiment 52: A dosage form described in any one of embodiments 25 to 51, wherein the coating formulation further comprises starch.

[0139] Embodiment 53: The dosage form of embodiment 52, wherein the starch comprises corn starch, potato starch, rice starch, wheat starch, tapioca starch, or a combination thereof.

[0140] Embodiment 54: The dosage form of embodiment 52 or embodiment 53, wherein the starch is present in the coating formulation in an amount of about 0% by weight to about 25% by weight, based on the combined weight of the coating formulation and the first active ingredient or the second active ingredient.

[0141] Embodiment 55: A dosage form described in any one of embodiments 25 to 54, wherein the multi-component dosage form exhibits little spotting after storage for about 18 days at 25° C. and 20% relative humidity.

[0142] Embodiment 56: A dosage form described in any one of embodiments 25 to 55, wherein the multi-component dosage form exhibits little spotting after storage for about 60 days at 25° C. and 20% relative humidity.

[0143] Embodiment 57: A dosage form described in any one of embodiments 25 to 56, wherein the multi-component dosage form exhibits little spotting after storage for about 120 days at 25° C. and 20% relative humidity.

[0144] Embodiment 58: A dosage form described in any one of embodiments 25 to 57, wherein the multi-component dosage form exhibits little spotting after storage for about 18 days at 45° C. and 20% relative humidity.

[0145] Embodiment 59: A dosage form described in any one of embodiments 25 to 58, wherein the multi-component dosage form exhibits little spotting after storage for about 60 days at 45° C. and 20% relative humidity.

[0146] Embodiment 60: A dosage form described in any one of embodiments 25 to 59, wherein the multi-component dosage form exhibits little spotting after storage for about 120 days at 45° C. and 20% relative humidity.

[0147] Embodiment 61: A dosage form described in any one of embodiments 25 to 60, wherein the multi-component dosage form exhibits little spotting after storage for about 18 days at 25° C. and 30% relative humidity.

[0148] Embodiment 62: A dosage form described in any one of embodiments 25 to 61, wherein the multi-component dosage form exhibits little spotting after storage for about 60 days at 25° C. and 30% relative humidity.

[0149] Embodiment 63: A dosage form described in any one of embodiments 25 to 62, wherein the multi-component dosage form exhibits little spotting after storage for about 120 days at 25° C. and 30% relative humidity.

[0150] Embodiment 64: A dosage form described in any one of embodiments 25 to 63, wherein the multi-component dosage form exhibits little spotting after storage for about 18 days at 45° C. and 30% relative humidity.

[0151] Embodiment 65: A dosage form described in any one of embodiments 25 to 64, wherein the multi-component dosage form exhibits little spotting after storage for about 60 days at 45° C. and 30% relative humidity.

[0152] Embodiment 66: A dosage form described in any one of embodiments 25 to 65, wherein the multi-component dosage form exhibits little spotting after storage for about 120 days at 45° C. and 30% relative humidity.

[0153] Embodiment 67: A multi-component dosage form, the dosage form comprising a coating formulation comprising choline, vitamin C, and shellac, wherein the coating formulation coats the choline.

[0154] Embodiment 68: A multi-component dosage form, the dosage form comprising a coating formulation comprising choline, vitamin C, and shellac, the coating formulation coating the vitamin C.

[0155] Embodiment 69: A multicomponent dosage form, the dosage form comprising choline, wherein the choline is coated with a first coating formulation comprising shellac, and vitamin C, wherein the vitamin C is coated with a second coating formulation comprising shellac.

[0156] 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 with a coating formulation comprising shellac; and including the active ingredient coated with the coating formulation in a dosage form.

[0157] Embodiment 71: The method of embodiment 70, wherein the active ingredient is vitamin C.

[0158] Embodiment 72: The method of embodiment 70 or embodiment 71, wherein the active ingredient is choline.

[0159] Embodiment 73: The method of any one of embodiments 70-72, wherein the active ingredients are choline and vitamin C.

[0160] Embodiment 74: The method of any one of embodiments 70 to 73, wherein the coating formulation further comprises a silicate.

[0161] Embodiment 75: The method of embodiment 74, wherein the silicate comprises silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or a combination thereof.

[0162] Embodiment 76: The method of embodiment 74 or embodiment 75, wherein the silicate is present in the coating formulation in an amount of about 0% by weight to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0163] Embodiment 77: The method of embodiment 75, wherein the silicon dioxide comprises colloidal silicon dioxide or fumed silica.

[0164] Embodiment 78: The method of any one of embodiments 70 to 77, wherein the coating formulation further comprises cellulose or a derivative thereof.

[0165] Embodiment 79: The method of embodiment 78, wherein the cellulose or a derivative thereof comprises microcrystalline cellulose, powdered cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hypromellose, carboxymethyl cellulose, or a combination thereof.

[0166] Embodiment 80: The method of embodiment 78 or embodiment 79, wherein the cellulose or derivatives thereof comprises hydroxypropyl cellulose.

[0167] Embodiment 81: The method of embodiment 80, wherein the hydroxypropyl cellulose is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient.

[0168] Embodiment 82: The method of embodiment 78 or embodiment 79, wherein the cellulose or a derivative thereof comprises microcrystalline cellulose.

[0169] Embodiment 83: The method of embodiment 82, wherein the microcrystalline cellulose is present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and the first active ingredient and the second active ingredient.

[0170] Embodiment 84: The method of embodiment 78 or embodiment 79, wherein the cellulose or a derivative thereof comprises ethyl cellulose.

[0171] Embodiment 85: The method of embodiment 84, wherein the ethylcellulose is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the first active ingredient or the second active ingredient.

[0172] Embodiment 86: The method of any one of embodiments 70 to 85, wherein the coating formulation further comprises starch.

[0173] Embodiment 87: The method of embodiment 86, wherein the starch comprises corn starch, potato starch, rice starch, wheat starch, tapioca starch, or a combination thereof.

[0174] Embodiment 88: The method of embodiment 86 or embodiment 87, wherein the starch is present in the coating formulation in an amount of about 0% by weight to about 25% by weight, based on the combined weight of the coating formulation and the first active ingredient or the second active ingredient.

[0175] Embodiment 89: The method of any one of embodiments 70 to 88, wherein the multicomponent dosage form exhibits little spotting after about 18 days of storage at 25° C. and 20% relative humidity.

[0176] Embodiment 90: The method of any one of embodiments 70 to 89, wherein the multi-component dosage form exhibits little spotting after storage for about 60 days at 25° C. and 20% relative humidity.

[0177] Embodiment 91: The method of any one of embodiments 70 to 90, wherein the multi-component dosage form exhibits little spotting after storage for about 120 days at 25° C. and 20% relative humidity.

[0178] Embodiment 92: The method of any one of embodiments 70 to 91, wherein the multicomponent dosage form exhibits little spotting after about 18 days of storage at 45° C. and 20% relative humidity.

[0179] Embodiment 93: The method of any one of embodiments 70 to 92, wherein the multicomponent dosage form exhibits little spotting after storage for about 60 days at 45° C. and 20% relative humidity.

[0180] Embodiment 94: The method of any one of embodiments 70 to 93, wherein the multicomponent dosage form exhibits little spotting after storage for about 120 days at 45° C. and 20% relative humidity.

[0181] Embodiment 95: The method of any one of embodiments 70 to 94, wherein the multicomponent dosage form exhibits little spotting after about 18 days of storage at 25° C. and 30% relative humidity.

[0182] Embodiment 96: The method of any one of embodiments 70 to 95, wherein the multicomponent dosage form exhibits little spotting after storage for about 60 days at 25° C. and 30% relative humidity.

[0183] Embodiment 97: The method of any one of embodiments 70 to 96, wherein the multicomponent dosage form exhibits little spotting after storage for about 120 days at 25° C. and 30% relative humidity.

[0184] Embodiment 98: The method of any one of embodiments 70 to 97, wherein the multicomponent dosage form exhibits little spotting after about 18 days of storage at 45° C. and 30% relative humidity.

[0185] Embodiment 99: The method of any one of embodiments 70 to 98, wherein the multi-component dosage form exhibits little spotting after storage for about 60 days at 45° C. and 30% relative humidity.

[0186] Embodiment 100: The method of any one of embodiments 70 to 99, wherein the multicomponent dosage form exhibits little spotting after storage for about 120 days at 45° C. and 30% relative humidity. EXAMPLES

[0187] Example 1: Exemplary Dosage Forms A dosage form of the present disclosure was made containing 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, phosphorus, 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 contain choline. When the formulation did not contain choline, hydroxypropyl cellulose was included in the formulation in the same amount, i.e., 280 mg. The amount of each component in the formulation is shown in Table 1. Table 1 [Table 1-1] [Table 1-2]

[0188] Figure 1 shows tablets containing vitamin C but no choline under different storage conditions after 18 days. Tablet compositions are shown in Table 2. Storage conditions ranged from 10% relative humidity (RH) to 30% RH, and 25°C to 45°C. Spotting occurred to some degree under each storage condition, with the most significant spotting occurring at higher temperatures and humidity. One tablet stored at 40°C and 75% RH showed significant spotting after only 24 hours. Table 2 [Table 2-1] [Table 2-2]

[0189] Figures 2A-2D show commercial tablets stored for 18 days under different conditions. Tablets in Figures 2A, 2B, and 2D did not contain choline, while the tablet in Figure 2C contained 30 mg of choline. All tablets contained vitamin C. Tablets were cut in half for the experiment. The tablet halves labeled "open" and "pristine" were two halves of the same tablet, while the tablets labeled "capped" were halves of a separate tablet. Tablets labeled "open" were stored for 24 hours at 40°C and 75% RH. Tablets labeled "capped" were also stored for 24 hours at 40°C and 75% RH, but covered with a cap in a humidity chamber. Tablets labeled "pristine" were stored at room temperature and 0% RH. Each tablet showed significant spotting in the "open" condition.

[0190] Figure 3 shows spotting for tablets containing choline and vitamin C stored for 18 days under different temperature and humidity conditions. Tablet composition is shown in Table 3. Temperature conditions tested were 25°C, 45°C, 65°C, and 85°C, and relative humidity conditions tested were 0%, 10%, 30%, and 60%. As can be seen from the figure, spotting accelerated as temperature and humidity increased. At 60% relative humidity, the tablets were almost completely black after 18 days, regardless of temperature. Table 3 [Table 3-1] [Table 3-2]

[0191] Figure 4 shows spotting for tablets containing choline and vitamin C under refrigerated conditions. The tablets had the tablet composition described in Table 3. The tablets were stored at 0% RH, 30% RH, and 60% RH for 18 days at 4°C. After 18 days, even under refrigerated conditions, the tablets stored at 60% RH still showed significant spotting.

[0192] Figures 5A and 5B show spotting for tablets containing vitamin C and various forms of choline compared to tablets not containing choline. Typical tablet compositions are listed in Table 4. Tablets were stored for 18 days at either 25°C or 45°C and either 10% or 30% relative humidity. One tablet not containing choline was used as a reference. Figure 5A shows the reference tablet and a tablet containing choline chloride and choline bitartrate. Figure 5B shows a tablet containing choline chloride crystals blended with 1.5% calcium chloride, choline chloride crystals blended with 1.5% trimagnesium citrate, and choline chloride blended with 2% magnesium stearate. As used throughout the remainder of this specification and Example 1, "choline chloride crystals blended with 1.5% calcium chloride" means that the choline chloride crystals are blended with 1.5% w / w calcium chloride based on the combined mass of the choline chloride and coating. In other words, for every 98.5 mg of choline chloride in the tablet, 1.5 mg of calcium chloride is blended. As can be clearly seen from Figures 5A-5B, spotting occurred under nearly all storage conditions with the addition of various forms of choline. In addition, the figures suggest that, in general, relative humidity has a large effect on the extent of spotting. Table 4 [Table 4]

[0193] Figure 6A shows spotting for tablets containing 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. Tablets without vitamin C are used as reference. The tablets were stored for 18 days at temperatures of 25°C or 45°C and relative humidity of 10%, 20%, or 30%. The tablets tested from top to bottom in Figure 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. As expected from previous tests, increasing temperature and relative humidity increased the degree of spotting for all of the various vitamin C forms. Some spotting occurred under all temperature and humidity conditions. Table 5 [Table 5]

[0194] Figure 6B shows spotting for tablets containing vitamin C and choline and various coating formulations. Tablet compositions are listed in Table 3. Tablets were stored for 18 days at temperatures of 25°C or 45°C and 20% or 30% relative humidity. Tablets tested from top to bottom in Figure 6B included vitamin C blended with 3.8% citrus bioflavonoids and 3.3% fatty acids, vitamin C coated with a mixture of 0.13% oleic acid, 1.12% ethylcellulose, 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. Spotting was significantly reduced compared to previous tests, but tablets still showed some spotting.

[0195] Figure 7 shows spotting for tablets containing both vitamin C and choline and various coating formulations. Tablet compositions are listed in Table 3. Tablets were stored for 18 days at temperatures of 25°C or 45°C and 20% or 30% relative humidity. Tablets tested from top to bottom in Figure 7 included tablets containing choline bitartrate coated with a mixture of shellac and talc, tablets containing vitamin C coated with a mixture of shellac and talc, tablets containing both vitamin C and choline bitartrate coated with a mixture of shellac and talc, and tablets containing choline bitartrate and vitamin C without coating. It is clear from Figure 7 that there was reduced spotting when vitamin C alone was coated with shellac compared to tablets containing choline bitartrate coated with shellac. However, tablets with both vitamin C and choline bitartrate coated with shellac showed little or no spotting.

[0196] Figure 8 shows the progression of spotting for tablets containing a coating formulation that included both vitamin C and choline, and a mixture of shellac and talc. The tablet composition is described in Table 3. The tablets were stored for 18 days at temperatures of 25°C or 45°C and a relative humidity of 30%. No spotting was observed for any of the tablets. However, due to regulations, talc cannot be used for certain medical applications. Therefore, more coating formulations were developed that did not contain talc for medical applications.

[0197] FIG. 9 shows the progression of spotting for tablets containing a shellac coating on vitamin C or on choline bitartrate. Tablet compositions are listed in Table 3. Percentages refer to the weight percent of active ingredient relative to the combined weight of active ingredient and coating, i.e., a 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 other additives such as talc, i.e., the coating contained only shellac. Tablets were stored at temperatures of 25° C. or 45° C. and relative humidity of 20% or 30% for 18 days. Images show tablets at 0, 4, 7, 11, 14, and 18 days. Tablets containing 87% vitamin C coated with shellac showed spotting only at high temperature and humidity. However, the remaining tablets showed little or no spotting.

[0198] Figure 10 shows the progression of spotting for tablets containing a shellac coating on vitamin C or choline bitartrate. Tablet compositions are described in Table 3. Tablets were stored for 18 days at temperatures of 25°C or 45°C and 20% or 30% relative humidity. Images show tablets at days 0, 4, 7, 11, 14, and 18. Tablets that did not contain vitamin C and tablets that contained uncoated ascorbic acid were included for reference. Tablets that contained shellac coated vitamin C and choline bitartrate showed little or no spotting.

[0199] FIG. 11 shows the progression of spotting for tablets containing a shellac coating on vitamin C or on choline bitartrate, or on both. The tablet composition is described in Table 3. The tablets were stored for 18 days at a temperature of 45° C. and a relative humidity of 20% or 30%. The images show the tablets on days 0, 4, 7, 11, 14, and 18. It can be clearly seen that the tablets that contained shellac-coated choline bitartrate and vitamin C showed no spotting. Furthermore, the tablets that contained either shellac-coated choline bitartrate or shellac-coated vitamin C still showed little or no spotting.

[0200] Coating formulations were made to coat choline bitartrate and ascorbic acid (vitamin C) within the dosage form. Table 6 shows the different formulations that were made. Table 6 [Table 6]

[0201] Example 2: Colorimeter measurements A HunterLab UltraScan VIS colorimeter was used to perform colorimetric analysis on the tablets. One or more of each tablet tested was reserved for use as the initial colorimeter measurement. The reserved tablet(s) were stored in a desiccator in the dark to prevent spotting.

[0202] Using a mortar and pestle, the tablets were crushed into a powder. The powder was then transferred to a 100 mL amber volumetric flask. 80-90 mL of distilled water was added to the flask. The flask was capped and the contents were shaken several times. The flask was then filled to the 100 mL mark with distilled water and shaken again.

[0203] 25 mL of liquid from the flask was then transferred to a 50 mL centrifuge tube. The tube was spun at 3200 rpm for 10 minutes. The liquid was decanted and poured into a clean colorimeter cuvette. The cuvette was placed in the colorimeter and the color spectrum of the liquid was measured. A reserved tablet was measured first and kept as a reference or origin. The total color difference (ΔE) was calculated. A ΔE of less than 1 is generally an unnoticeable color change and is therefore most desirable.

[0204] 12A-12G show colorimeter measurements for tablets containing coating formulations of the present disclosure. All tablets were stored at 30% RH for 18 days. FIG. 12A shows colorimeter measurements from tablets containing coating formulations 1 and 4 described in Table 6. FIG. 12B shows colorimeter measurements from tablets containing coating formulations 1 and 5 described in Table 6. FIG. 12C shows colorimeter measurements from tablets containing coating formulations 2 and 4 described in Table 6. FIG. 12D shows colorimeter measurements from tablets containing coating formulations 2 and 5 described in Table 6. FIG. 12E shows colorimeter measurements from tablets containing coating formulations 3 and 4 described in Table 6. FIG. 12F shows colorimeter measurements from tablets containing coating formulations 3 and 5 described in Table 6. FIG. 12G shows colorimeter measurements from tablets containing coating formulations 1 and 5 described in Table 6 with the addition of talc. Colorimeter measurements were taken at various times over 18 days.

[0205] Figure 13 shows the ΔE measured for each tablet measured in Figures 12A-12G on days 0, 4, 7, 11, 14, and 18, as well as the average ΔE measured for each tablet. Overall, the average ΔE ranged from 0.85 to 2.03, indicating a low degree of color change between tablets.

[0206] 14A-14B show colorimeter measurements for tablets that did not contain the coating formulation of the present disclosure. FIG. 14A shows colorimeter measurements for tablets that contained vitamin C and no choline. FIG. 14B shows colorimeter measurements from tablets that contained vitamin C and choline chloride. It is clear that the tablets measured in FIGS. 14A-14B showed a much larger color change compared to the tablets shown in FIGS. 12A-12G. In general, tablets without the coating formulation of the present disclosure had an average ΔE of about 7-10. For one tablet that contained choline chloride coated with calcium chloride, the ΔE at day 18 was 68.7, showing a large color change from the reference tablet.

[0207] Figure 14C shows the solutions used in the colorimeter experiment of Figures 14A-14B after 18 days. The cuvette on the left is a sample for tablets that contained vitamin C and no choline. The cuvette on the right is a sample for tablets that contained vitamin C and choline chloride.

Claims

1. A coating formulation comprising shellac, said coating formulation coating at least one active ingredient which is vitamin C or choline in a multi-component dosage form.

2. 10. The coating formulation of claim 1, wherein the at least one active ingredient has a concentration of about 50.0% to about 95.0% by weight, based on the total weight of the at least one active ingredient and the coating formulation.

3. the at least one active ingredient comprises vitamin C, the vitamin C being, for example, 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 combination thereof; or The at least one active ingredient comprises choline, such as choline chloride, choline bitartrate, phosphatidylcholine, choline dihydrogen citrate, alphaglycerylphosphorylcholine, cytidine diphosphate-choline, choline folate, esters 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 coating formulation according to claim 1.

4. 10. The coating formulation of claim 1, wherein the shellac is present in an amount of about 1% to about 50% by weight, based on the combined weight of the at least one active ingredient and the coating formulation.

5. The coating formulation (i) further comprising a silicate, such as silicon dioxide, bentonite, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, silicified microcrystalline cellulose, or a combination thereof, wherein optionally, the silicate is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient; and optionally, the silicon dioxide comprises colloidal silicon dioxide or fumed silica; (ii) further comprising cellulose or a derivative thereof, such as microcrystalline cellulose, powdered cellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, hypromellose, carboxymethylcellulose, or a combination thereof, or such as hydroxypropylcellulose, ethylcellulose, or microcrystalline cellulose, optionally wherein the hydroxypropylcellulose or ethylcellulose is present in the coating formulation in an amount of about 0% to about 10% by weight, based on the combined weight of the coating formulation and the at least one active ingredient, or optionally wherein the microcrystalline cellulose is present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and the first active ingredient and the second active ingredient; (iii) further comprising a starch, such as corn starch, potato starch, rice starch, wheat starch, tapioca starch, or a combination thereof, optionally present in the coating formulation in an amount of about 0% to about 25% by weight, based on the combined weight of the coating formulation and the first active ingredient or the second active ingredient; The coating formulation according to claim 1.

6. A multi-component dosage form comprising a coating formulation described in any one of claims 1 to 5.

7. 7. The multicomponent dosage form of claim 6, wherein the vitamin C or choline is present in the multicomponent dosage form in an amount of from about 1 mg to about 2000 mg.

8. the shellac is present in an amount of about 1% to about 50% by weight, based on the total weight of the at least one active ingredient and the coating formulation; and / or the at least one active ingredient is present in an amount of about 50.0% to about 95.0% by weight, based on the combined weight of the at least one active ingredient and the coating formulation; 7. The multicomponent dosage form of claim 6.

9. the at least one active ingredient comprises vitamin C and choline, and the choline is not coated with the coating formulation; the at least one active ingredient comprises choline, the multi-component dosage form further comprises vitamin C, and the vitamin C is not coated with the coating formulation; or the at least one active ingredient comprises vitamin C, the multi-component dosage form further comprises choline, and the choline is not coated with the coating formulation; 7. The multicomponent dosage form of claim 6.

10. 7. The multicomponent dosage form of claim 6, wherein the multicomponent dosage form further comprises an additional active ingredient that is not coated by the coating formulation.

11. The multi-component dosage form comprises: After about 18 days of storage at 25°C and 20% relative humidity, After about 60 days of storage at 25°C and 20% relative humidity, After approximately 120 days of storage at 25°C and 20% relative humidity, After about 18 days of storage at 45°C and 20% relative humidity, After approximately 60 days of storage at 45°C and 20% relative humidity, After approximately 120 days of storage at 45°C and 20% relative humidity, After about 18 days of storage at 25°C and 30% relative humidity, After about 60 days of storage at 25°C and 30% relative humidity, After about 120 days of storage at 25°C and 30% relative humidity, After about 18 days of storage at 45°C and 30% relative humidity, After about 60 days of storage at 45°C and 30% relative humidity, or After approximately 120 days of storage at 45°C and 30% relative humidity, 7. The multicomponent dosage form of claim 6, which exhibits little spotting.

12. Choline and Vitamin C and a coating formulation comprising shellac, The coating formulation coats the choline.

7. The multicomponent dosage form of claim 6.

13. Choline and Vitamin C and a coating formulation comprising shellac, The coating formulation coats the vitamin C.

7. The multicomponent dosage form of claim 6.

14. A method for treating a choline-containing steroid deficiency, comprising: Vitamin C coated with a second coating formulation comprising shellac; 7. The multicomponent dosage form of claim 6.

15. 1. A method for preventing spotting in a dosage form, said method comprising: providing an active ingredient comprising at least one of vitamin C and choline; coating the active ingredient with a coating formulation comprising shellac; Including the active ingredient coated with the coating formulation in a dosage form; A method comprising:

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