Soft gel capsule and method for marking soft gel capsule

Abstract

A soft gel capsule is provided comprising a filler material and a shell composition. The shell composition comprises a marking formulation comprising a marking component. The marking component includes a metal oxide. Laser irradiation is applied to the soft gel capsule at a wavelength of from about 1000 nm to about 2200 nm such that the marker component produces a visible effect. A labeling method and a labeled formulation are also provided.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 427,533, filed on November 23, 2022, the entire contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] The present invention relates to a soft gel capsule for encapsulating a fill composition comprising a shell composition, wherein the shell composition comprises a marking component. More particularly, the present invention relates to applying laser irradiation to the soft gel capsule at a wavelength of about 1000 nm to about 2200 nm such that the marking component provides a visible effect. Background Art

[0004] In the pharmaceutical industry, labeling capsules to identify the product type, dosage, manufacturer, and other identifying information is a good manufacturing practice. Several methods are available for labeling hard and soft capsules. These methods are used to label the capsule skin and / or the capsule shell.

[0005] Some of these methods include ink printing, carbon dioxide (CO2) lasers, or UV lasers. During the ink printing method, ink can be deposited onto the capsule skin using various methods, such as inkjet printing, offset printing, or pad printing. A variety of colors can be used in the ink printing method. However, the ink printing method has its drawbacks. For example, this method contacts the surface of the capsule. Because the ink is soluble in certain solvents, it can be wiped off. If the solvent within the capsule migrates to the surface of the capsule skin, the ink can also be wiped off.

[0006] During the CO2 laser method, a CO2 laser is used to engrave into the capsule skin. As it engraves, white marks appear in the capsule skin or shell. This is believed to be due to changes in the reflectivity of the engraved material. A disadvantage of this method is that oil on the capsule surface may fill and flatten the engraved surface, potentially obscuring the visibility of the engraving.

[0007] Another common method for marking capsules is with UV lasers. Typically, titanium dioxide (TiO2) is added to the capsule material, causing it to react to the UV laser by changing color. Typically, the reaction of the TiO2 results in a dark marking on the capsule. Recently, TiO2 has been discouraged from industrial use. Therefore, there is a need in the art for an alternative marking component. Summary of the Invention

[0008] In one embodiment of the present invention, a soft gel capsule is provided. The soft gel capsule comprises a filler material and a shell composition. The shell composition may comprise a marking formulation including a marking component. Laser irradiation may be applied to the soft gel capsule of the present disclosure using a fiber laser at a wavelength of about 1000 nm to about 2200 nm, such that the marking component provides a visible effect.

[0009] In one embodiment of the soft gel capsule, the marking component can include a metal oxide. In some embodiments, the metal oxide can include iron oxide. The iron oxide can include iron oxide red, iron oxide yellow, iron oxide brown, iron oxide black, iron oxide green, iron oxide blue, or a combination thereof.

[0010] In some embodiments, the marking formulation may further comprise a plasticizer and gelatin. In some embodiments, the marking formulation may be substantially free of titanium dioxide. In some embodiments, the marking formulation does not comprise titanium dioxide.

[0011] In some embodiments, laser irradiation can be applied to the soft gel capsule at a wavelength of about 1200 nm to about 2000 nm. In one embodiment, laser irradiation can be achieved using a fiber laser.

[0012] In another embodiment of the present disclosure, a method for marking a soft gel capsule is provided. The method may include irradiating the soft gel capsule with a laser, wherein the soft gel capsule comprises a shell composition and a filler material, wherein the shell composition may comprise a marking formulation having a marking component.

[0013] In some embodiments of the method, the irradiation can be performed using a wavelength greater than about 1000 nm. In some embodiments, the irradiation can be performed using a wavelength of about 1000 nm to about 2200 nm, about 1200 nm to about 2000 nm, or about 1400 nm to about 1800 nm. In some embodiments, the irradiation can be performed using a fiber laser.

[0014] In some embodiments of the method, the marking component provides a visible effect after irradiation of the soft gel capsule.

[0015] In another embodiment of the present disclosure, a marking formulation is provided. The marking formulation may include a marking component comprising a metal oxide, a plasticizer, and gelatin. Laser irradiation may be applied to the marking formulation at a wavelength of about 1000 nm to about 2200 nm such that the marking component provides a visible effect.

[0016] In one embodiment of the marking formulation, the metal oxide can include iron oxide. In some embodiments, the iron oxide can include iron oxide red, iron oxide yellow, iron oxide brown, iron oxide black, iron oxide green, iron oxide blue, or a combination thereof.

[0017] In some embodiments of the marking formulation, the marking component can be included in an amount of about 0.001 wt % to about 10 wt %, about 0.005 wt % to about 9 wt %, about 0.01 wt % to about 8 wt %, about 0.05 wt % to about 7 wt %, about 0.1 wt % to about 6 wt %, about 0.5 wt % to about 5 wt %, about 1 wt % to about 4 wt %, about 1.5 wt % to about 3 wt %, or about 2 wt % to about 2.5 wt %, based on the total weight of the marking formulation.

[0018] In some embodiments of the marking formulation, the metal oxide can be included in an amount of about 1 gram to about 5 grams, about 1.2 grams to about 4.5 grams, about 1.4 grams to about 4 grams, about 1.6 grams to about 3.5 grams, about 1.8 grams to about 3 grams, or about 2 grams to about 2.5 grams, based on the total weight of 100 grams of the marking formulation.

[0019] In some embodiments of the marking formulation, the plasticizer may be included in an amount from about 5 wt % to about 40 wt %, from about 10 wt % to about 35 wt %, from about 15 wt % to about 30 wt %, or from about 20 wt % to about 25 wt %, based on the total weight of the marking formulation.

[0020] In some embodiments of the marking formulation, gelatin can be included in an amount from about 20 wt % to about 70 wt %, from about 25 wt % to about 65 wt %, from about 30 wt % to about 60 wt %, from about 35 wt % to about 55 wt %, or from about 40 wt % to about 50 wt %, based on the total weight of the marking formulation.

[0021] In some embodiments, the gelatin can be type A gelatin, type B gelatin, animal hide gelatin, bone gelatin, or a combination thereof. In some embodiments, the gelatin can be 150 bloom gelatin, 200 bloom gelatin, 250 bloom gelatin, or a combination thereof.

[0022] In some embodiments, the plasticizer can be glycerol, glycerin, sorbitol, sorbitan solution, triacetin, polysorbate, or a combination thereof.

[0023] In some embodiments, the marking formulation is substantially free of titanium dioxide. In other embodiments, the marking formulation does not comprise titanium dioxide. In some embodiments, the marking formulation may further comprise water. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The disclosure described herein is illustrated by way of example and not limitation in the accompanying figures.

[0025] The graph shows the results of the laser irradiation test of the example. DETAILED DESCRIPTION

[0026] The detailed description set forth below is intended only as a description of presently preferred embodiments of the invention and is not intended to represent the only form in which the invention may be constructed or utilized. The description sets forth the functions, components, and methods of implementing the invention in conjunction with the illustrated embodiments. However, it should be understood that the same or equivalent functions and features may be achieved by different embodiments that are also intended to be encompassed within the spirit and scope of the claims.

[0027] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an active pharmaceutical ingredient" includes a single active pharmaceutical ingredient as well as a mixture of two or more different active pharmaceutical ingredients, and reference to "an excipient" includes a single excipient as well as a mixture of two or more different excipients, etc.

[0028] As used herein, the term "about" in relation to a measured quantity refers to the normal variation of the measured quantity as would be expected by one of ordinary skill in the art when making the measurements and exercising a degree of care commensurate with the precision of the measurement objective and the measuring equipment. In certain embodiments, the term "about" includes ±5% of the recited number, such that "about 10" would include 9.5 to 10.5.

[0029] Recitation of ranges of values ​​herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or clearly contradicted by context.

[0030] The use of any and all examples or exemplary language (e.g., "such as") provided herein is intended merely to illustrate the particular materials and methods and does not limit the scope. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the disclosed materials and methods.

[0031] As used herein, the terms "active agent," "active ingredient," "active pharmaceutical ingredient," "API," and "drug" refer to any material intended to produce a therapeutic, prophylactic, or other desired effect, whether or not approved by a governmental agency for that purpose. These terms, with respect to a particular agent, encompass all pharmaceutically active agents, all pharmaceutically acceptable salts, complexes, stereoisomers, crystalline forms, co-crystals, ethers, esters, hydrates, solvates, and mixtures thereof, wherein the form is pharmaceutically active.

[0032] As used herein, "shell" or "shell composition" refers to the shell of a soft gel capsule that encapsulates the fill material.

[0033] As used herein, "fill material" or "fill" refers to the composition encapsulated by the shell.

[0034] As used herein, "free or substantially free" means that the composition includes less than about 1 wt%, less than about 0.5 wt%, less than about 0.25 wt%, less than about 0.1 wt%, less than about 0.05 wt%, less than about 0.01 wt%, or 0 wt% of a component.

[0035] In certain embodiments, the present invention relates to soft gel capsules that may include a filler material and a shell composition. The shell composition may include a marking component, wherein laser irradiation is applied to the soft gel capsule at a wavelength of about 1000 nm to about 2200 nm so that the marking component provides a visible effect. In some embodiments, the visible effect may include a color change. In another embodiment, the visible effect may be caused by foaming during the laser irradiation. In certain embodiments, it has been found that when laser irradiation is applied to the capsule, the marking component (e.g., iron oxide) causes a visible effect, such as a change to a darker pigmentation, such as black, or causes foaming on the capsule.

[0036] In some embodiments, the marking component may comprise a metal oxide. In certain embodiments of the soft gel capsule, the metal oxide may comprise iron oxide. The iron oxide may be iron oxide red, iron oxide yellow, iron oxide black, iron oxide brown, iron oxide green, iron oxide blue, or a combination thereof. In certain embodiments of the soft gel capsule, the marking component does not comprise titanium dioxide. In other embodiments of the soft gel capsule, the marking component is substantially free of titanium dioxide.

[0037] In some embodiments, the shell composition may further comprise a plasticizer and gelatin.

[0038] In some embodiments of soft gel capsules, laser irradiation is achieved by using a fiber laser. Without being limited by theory, the inventors of this case believe that the fiber laser reacts with the marking component in the shell composition and causes color change by the heat of the fiber laser. In certain embodiments, laser irradiation can be applied to soft gel capsules with a wavelength of about 1000nm, about 1050nm, about 1100nm, about 1150nm, about 1200nm, about 1250nm, about 1300nm, about 1350nm, about 1400nm, about 1450nm, about 1500nm, about 1550nm, about 1600nm, about 1650nm, about 1700nm, about 1750nm, about 1800nm, about 1850nm, about 1900nm, about 1950nm, about 2000nm, about 2050nm, about 2100nm, about 2150nm or about 2200nm or any value therein.

[0039] In some embodiments, the shell can comprise a synthetic polymer, a natural gelling agent, a buffer, a plasticizer, and water. The shell can be vegetarian and free of gelatin and / or starch (e.g., modified starch). The shell can be reprocessed and / or recycled so that any unused material (e.g., gel mass of the shell composition) can be formed into a net and stored until further processing is required.

[0040] In some embodiments, the synthetic polymer can be at least one of poly(N-vinyl lactam), povidone, crospovidone, maleic anhydride copolymer, poly(2-ethyl-2-oxazoline), poly(ethyleneimine), polyurethane hydrogel, acrylic polymer, methacrylic polymer, methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, aminoethyl acrylate, maleic anhydride, polymaleic acid, polyacrylamide, poly(methacrylamide), poly(dimethylacrylamide), poly(N-isopropylacrylamide), Polyvinyl ether, polyvinyl acetate, polyvinyl acetate phthalate, polyimine, polyethyleneimine, polyurethane hydrogel, chitosan, polysaccharide gum, zein, shellac, ammoniated shellac, shellac acetyl alcohol, shellac n-butyl stearate, esters thereof, homopolymers thereof, copolymers thereof, block copolymers thereof, graft copolymers thereof, and combinations thereof. In an embodiment, the synthetic polymer may comprise povidone. In embodiments, the amount of synthetic polymer can be from about 10 wt % to about 50 wt %, or from about 15 wt % to about 40 wt %, or from about 20 wt % to about 30 wt %, or about 24 wt %, or about 25 wt %, or about 26 wt %, or about 27 wt %, or about 28 wt %, or about 29 wt %, or about 30 wt %, or about 31 wt %, based on the weight of the shell composition.

[0041] In some embodiments, the natural gelling agent may include at least one of carrageenan, xanthan gum, agar or pectin, sugar, sugar-derived alcohol, starch, pregelatinized starch, cellulose derivatives, cellulose polymers, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, attapulgite, bentonite, dextrin, alginate, kaolin, lecithin, magnesium aluminum silicate, carbomer, carbopol, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, silicon dioxide, curdlan, furcellaran, egg white powder, whey protein, soy protein, chitosan, and sodium lauryl sulfate. In some embodiments, the natural gelling agent may include carrageenan. The carrageenan may be at least one of iota carrageenan, kappa carrageenan, and lambda carrageenan. In certain embodiments, the natural gelling agent may be iota carrageenan. In some embodiments, the amount of natural gelling agent can be from about 0.1 wt% to about 15 wt%, or from about 0.5 wt% to about 14 wt%, or from about 1 wt% to about 13 wt%, or from about 2 wt% to about 12 wt%, or from about 3 wt% to about 12 wt%, or from about 4 wt% to about 11 wt%, or from about 5 wt% to about 10 wt%, or from about 6 wt% to about 9 wt%, or about 5 wt%, or about 5.5 wt%, or about 6.0 wt%, or about 6.5 wt%, or about 7.0 wt%, or about 7.5 wt%, or about 8.0 wt%, or about 8.5 wt%, or about 9.0 wt%, based on the weight of the shell composition.

[0042] In some embodiments, the shell may comprise a film-forming polymer and an optional plasticizer. The film-forming polymer may be an animal-derived polymer, a non-animal-derived polymer, or a combination thereof. The animal-derived polymer may comprise gelatin. The gelatin in the shell composition may include, but is not limited to, Type A gelatin, Type B gelatin, hide gelatin, fish gelatin, porcine gelatin, and / or bone gelatin, used alone or in combination. In one embodiment, the gelatin is a Type A medium to high bloom gelatin. In one embodiment, the gelatin is a Type B medium to high bloom gelatin. Medium bloom is when the bloom is about 70 grams to about 160 grams. High bloom is when the bloom is about 175 grams or more, or about 175 grams to about 300 grams. In one embodiment, the gelatin is 250 bloom gelatin. In another embodiment, only one type of gelatin is present. In yet another embodiment, the gelatin is a combination of at least two types of gelatin. The non-animal-derived polymer may comprise carrageenan.

[0043] The plasticizer can be glycerol, glycerol, sorbitol, sorbitol sorbitan solution, polyethylene sorbitan monooleate or a combination thereof. Other suitable plasticizers may include, but are not limited to, sugar alcohol plasticizers such as isomalt, maltitol, xylitol, erythritol, adonitol, galactitol, pentaerythritol or mannitol; or polyol plasticizers such as diglycerol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, dipropylene glycol, polyethylene glycol up to 10,000 MW, neopentyl glycol, propylene glycol, 1,3-propylene glycol, 2-methyl-1,3-propanediol, trimethylolpropane, polyether polyols, ethanolamine; and mixtures thereof. Other exemplary plasticizers may also include, but are not limited to, low molecular weight polymers, oligomers, copolymers, oils, small organic molecules, low molecular weight polyols with aliphatic hydroxyl groups, ester-type plasticizers, glycol ethers, poly(propylene glycol), multi-block polymers, single-block polymers, citrate-type plasticizers, and triacetin. Such plasticizers may include 1,2-butanediol, 2,3-butanediol, styrene glycol, monopropylene glycol monoisopropyl ether, propylene glycol monoethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether, sorbitan lactate, ethyl lactate, butyl lactate, ethyl glycolate, dibutyl sebacate, acetyl tributyl citrate, triethyl citrate, glyceryl monostearate, polysorbate 80, acetyl triethyl citrate, tributyl citrate, and allyl glycolate, and mixtures thereof.

[0044] The shell may further comprise additional components. The additional components may comprise dextrose, pectin, a gelling agent, a thickening agent, a buffer, water or a combination thereof. The shell may further comprise pullulan.

[0045] In certain embodiments, shell composition can comprise pectin.In certain embodiments, pectin can be low methoxyl pectin.In certain embodiments, pectin can be amidated pectin, non-amidated pectin or its combination.In one embodiment, pectin is low methyl ester (LM) pectin with a degree of esterification lower than 50.In certain embodiments, pectin is LMS-318, SPL-12, LM-102AS-Z and / or LM-12CG-Z.In other embodiments, low methoxyl (LM) pectin can be LM pectin (P-25), LM pectin (445C), LM pectin (100C) or its combination.

[0046] In some embodiments, the shell composition may further comprise a gelling agent. In some embodiments, the gelling agent may be gellan gum. For example, the gellan gum may be Kelcogel CG-LA gellan gum. In other embodiments, the gelling agent may be a non-animal derived gelling agent. The non-animal derived gelling agent may comprise carrageenan, starch, xanthan gum, agar, pectin, sugar, sugar-derived alcohol, cellulose derivatives, cellulose polymers, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, attapulgite, bentonite, dextrin, alginate, kaolin, lecithin, magnesium aluminum silicate, carbomer, carbopol, silicon dioxide, curdlan, furcellaran, egg white powder, whey protein, soy protein, chitosan, or a combination thereof.

[0047] In some embodiments, the shell composition may optionally include a synthetic polymer. The synthetic polymer may be polyvinyl alcohol, a polyvinyl alcohol-polyethylene glycol graft copolymer, a high molecular weight polyethylene glycol, povidone, a surfactant, a nonionic triblock copolymer, or a combination thereof. In some embodiments, the synthetic polymer may be a nonionic triblock copolymer. In some embodiments, the nonionic triblock copolymer may include polyethylene oxide and polypropylene oxide blocks. In some embodiments, the surfactant may be sodium lauryl sulfate.

[0048] In some embodiments, the shell composition may include a buffer. The buffer may be disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium bicarbonate, sodium citrate, disodium phosphate, calcium phosphate, calcium hydrogen phosphate, tricalcium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, and combinations thereof.

[0049] In some embodiments, the shell composition may optionally include additional agents such as colorants, flavorings, sweeteners, fillers, antioxidants, diluents, pH adjusters, or other pharmaceutically acceptable excipients or additives, such as synthetic dyes and mineral oxides.

[0050] Exemplary suitable colorants can include, but are not limited to, colors such as white, black, yellow, blue, green, pink, red, orange, purple, indigo, and brown. In certain embodiments, the color of the dosage form can indicate the contents (e.g., one or more active ingredients) contained therein. It will be understood by those skilled in the art that the colorant of the shell can be separate and different from the colorant of the marking component.

[0051] Exemplary suitable flavoring agents may include, but are not limited to, "flavor extracts" obtained by extracting a portion of a raw material (e.g., animal or plant material), typically by using a solvent such as ethanol or water; natural flavors obtained by extracting essential oils from flowers, fruits, roots, etc., or from the entire plant.

[0052] Additional exemplary flavoring agents that may be in dosage form may include, but are not limited to, breath freshening compounds such as menthol, spearmint, and cinnamon; coffee beans; other flavors or aromas, such as fruit flavors (e.g., cherry, orange, grape, etc.), especially those used for oral hygiene, and active agents for tooth and mouth cleaning, such as quaternary ammonium bases. The effect of the flavor may be enhanced using flavor enhancers such as tartaric acid, citric acid, vanillin, and the like.

[0053] Exemplary sweeteners may include, but are not limited to, one or more artificial sweeteners, one or more natural sweeteners, or combinations thereof. Artificial sweeteners include, for example, acesulfame potassium and its various salts, such as potassium salts (available as available); Alitame; Aspartame (available as and Aspartame-acesulfame potassium salt (available as commercially available); neohesperidin dihydrochalcone; naringin dihydrochalcone; dihydrochalcone compounds; neotame; cyclamate; saccharin and its various salts, such as sodium salt (available as Sweet'N commercially available); Stevia; chlorinated derivatives of sucrose, such as sucralose (available as and Natural sweeteners include, for example, glucose, dextrose, invert sugar, fructose, sucrose, glycyrrhizin; monoammonium glycyrrhizinate (available under the trade name sold); stevia (stevioside), natural strong sweeteners (such as monk fruit), polyols (such as sorbitol, mannitol, xylitol, erythritol, etc.).

[0054] In some embodiments of the soft gel capsule, a methacrylic acid copolymer can be included in the shell composition. In some embodiments, the methacrylic acid copolymer can be Kollicoat MAE 100P.

[0055] The thickener can be starch, a starch derivative, or a modified starch. The starch or starch derivative can be hydroxypropylated tapioca starch, hydroxypropylated corn starch, potato starch, or pregelatinized modified corn starch. Modified starch includes, for example, hydroxypropylated starch, acid-thinned starch, and the like. Generally, modified starch is a product prepared by chemically treating starch, such as acid-treated starch, enzyme-treated starch, oxidized starch, cross-linked starch, and other starch derivatives.

[0056] The buffer and / or alkalizing agent can be, but is not limited to, ammonium hydroxide, sodium hydroxide, sodium carbonate, sodium citrate, trisodium phosphate and / or disodium phosphate. In one embodiment, the buffer is disodium phosphate.

[0057] In some embodiments of soft gel capsules, the fill material may include at least one active pharmaceutical ingredient.

[0058] The fill composition of the soft gel composition may further comprise additional ingredients. Those additional ingredients may be flavorings, sweeteners, colorants, fillers, antioxidants, synthetic dyes, mineral oxides, water, acrylate copolymers, xanthan gum, glycerin, butylene glycol, aminomethyl propanol, aloe barbaensis leaf extract, active ingredients, lipids, or combinations thereof.

[0059] In some embodiments, the lipid can be selected from, but not limited to, the group consisting of: almond oil, argan oil, avocado oil, borage seed oil, canola oil, cashew oil, castor oil, hydrogenated castor oil, cocoa butter, coconut oil, rapeseed oil, corn oil, cottonseed oil, grapeseed oil, hazelnut oil, hydroxylated lecithin, lecithin, linseed oil, macadamia oil, mango butter, abaca oil, mongongo nut oil, olive oil, palm kernel oil, palm oil, peanut oil, walnut oil, perilla oil, pine nut oil, pistachio oil, pumpkin seed oil, rice bran oil, safflower oil, sesame oil, shea butter, soybean oil, sunflower oil, hydrogenated vegetable oil, walnut oil, and watermelon seed oil. Other oils and fats may include, but are not limited to, fish oil (ω-3), krill oil, animal or vegetable fats (e.g., in their hydrogenated forms), free fatty acids, and mono-, di-, and triglycerides with C8-, C10-, C12-, C14-, C16-, C18-, C20-, and C22-fatty acids, and combinations thereof.

[0060] In some embodiments, the antioxidant may be butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), or a combination thereof.

[0061] In certain embodiments of the present invention, the soft gel may be spherical, elliptical, oblong, or twist-off.

[0062] In another embodiment of the present disclosure, a method for marking a soft gel capsule is provided. The method may include irradiating the soft gel capsule with a laser, wherein the soft gel capsule comprises a shell composition and a filler material. The shell composition may include a marking component.

[0063] In some embodiments of the method, the irradiation can be performed using a wavelength greater than about 1000 nm. In another embodiment of the method, the irradiation can be performed using a wavelength of about 1000 nm to about 2200 nm, about 1200 nm to about 2000 nm, or about 1500 nm to about 1800 nm.

[0064] In some embodiments of the method, irradiating can be performed using a fiber laser.

[0065] In one embodiment of the method, the marking component in the shell composition can provide a visible effect after irradiation of the soft gel capsule. In some embodiments, the visible effect can include a color change. The color change can include darkening of the marking component in the shell composition. In some embodiments, the color change can include forming a black pigmentation in the shell composition to form the marking. In another embodiment, the visible effect can be caused by foaming from the laser irradiation.

[0066] In one embodiment of the method, the laser can have a power of about 10 watts to about 30 watts, about 15 watts to about 25 watts, or about 17.5 watts to about 22.5 watts.

[0067] In some embodiments of the method, the marking component may comprise a metal oxide. In certain embodiments, the metal oxide may comprise iron oxide. The iron oxide may be iron oxide red, iron oxide yellow, iron oxide black, iron oxide brown, or a combination thereof. In certain embodiments, the marking component does not comprise titanium dioxide. In other embodiments of the soft gel capsule, the marking component is substantially free of titanium dioxide. It is believed that titanium dioxide is needed to achieve a color change in the shell (e.g., gelatin shell) of the soft gel capsule. The application has found that other metal oxides, such as iron oxide, can achieve similar color changes without the use of titanium dioxide.

[0068] In some embodiments, the shell composition may further comprise a plasticizer and gelatin.

[0069] Without being limited by theory, the inventors believe that the fiber laser reacts with the marking component in the shell composition and causes the color change through the heat of the fiber laser. In some embodiments, the laser irradiation can be applied to the soft gel capsule at a wavelength of about 1000 nm, about 1050 nm, about 1100 nm, about 1150 nm, about 1200 nm, about 1250 nm, about 1300 nm, about 1350 nm, about 1400 nm, about 1450 nm, about 1500 nm, about 1550 nm, about 1600 nm, about 1650 nm, about 1700 nm, about 1750 nm, about 1800 nm, about 1850 nm, about 1900 nm, about 1950 nm, about 2000 nm, about 2050 nm, about 2100 nm, about 2150 nm, or about 2200 nm, or any value therein.

[0070] In another embodiment, a marking formulation is provided. The marking formulation may include a marking component, a plasticizer, and gelatin. In some embodiments, laser irradiation may be applied to the marking formulation at a wavelength of about 1000 nm to about 2200 nm such that the marking component provides a visible effect. The visible effect may include a color change. In some embodiments, the visible effect may be caused by foaming from the laser irradiation.

[0071] In some embodiments, the marking component may comprise a metal oxide. In certain embodiments, the metal oxide may comprise iron oxide. The iron oxide may be red iron oxide, yellow iron oxide, black iron oxide, brown iron oxide, or a combination thereof. In certain embodiments, the marking component does not comprise titanium dioxide. In other embodiments of the soft gel capsule, the marking component is substantially free of titanium dioxide.

[0072] In one embodiment, the marking component can be included in the marking formulation in an amount of 0.001 wt % to about 10 wt %, about 0.005 wt % to about 9 wt %, about 0.01 wt % to about 8 wt %, about 0.05 wt % to about 7 wt %, about 0.1 wt % to about 6 wt %, about 0.5 wt % to about 5 wt %, about 1 wt % to about 4 wt %, about 1.5 wt % to about 3 wt %, or about 2 wt % to about 2.5 wt %, based on the total weight of the marking formulation. In some embodiments, the marker component can be included in an amount of about 0.001 wt%, about 0.002 wt%, about 0.005 wt%, about 0.01 wt%, about 0.05 wt%, about 0.1 wt%, about 0.25 wt%, about 0.5 wt%, about 0.75 wt%, about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt%, or any value therein, based on the total weight of the marker formulation.

[0073] In some embodiments, the metal oxide can be included in an amount of about 1 gram to about 5 grams, about 1.2 grams to about 4.5 grams, about 1.4 grams to about 4 grams, about 1.6 grams to about 3.5 grams, about 1.8 grams to about 3 grams, or about 2 grams to about 2.5 grams per 100 grams of the marking formulation. In other embodiments, the metal oxide can be included in the marking formulation in an amount of about 1 gram, about 1.2 grams, about 1.4 grams, about 1.6 grams, about 1.8 grams, about 2 grams, about 2.5 grams, about 3 grams, about 3.5 grams, about 4 grams, about 4.5 grams, or about 5 grams per 100 grams of the marking formulation.

[0074] In some embodiments, the plasticizer can be included in the marking formulation in an amount of about 5 wt % to about 40 wt %, about 10 wt % to about 35 wt %, about 15 wt % to about 30 wt %, or about 20 wt % to about 25 wt %, based on the total weight of the marking formulation. In some embodiments, the plasticizer can be included in an amount of about 5 wt %, about 10 wt %, about 15 wt %, about 20 wt %, about 25 wt %, about 30 wt %, about 35 wt %, or about 40 wt %, or any value therein.

[0075] In some embodiments, gelatin can be included in the marking formulation in an amount of about 20 wt % to about 70 wt %, about 25 wt % to about 65 wt %, about 30 wt % to about 60 wt %, about 35 wt % to about 55 wt %, or about 40 wt % to about 50 wt %, based on the total weight of the marking formulation. In some embodiments, gelatin can be included in an amount of about 20 wt %, about 25 wt %, about 30 wt %, about 35 wt %, about 40 wt %, about 45 wt %, about 50 wt %, about 55 wt %, about 60 wt %, about 65 wt %, or about 70 wt %, based on the total weight of the marking formulation.

[0076] In some embodiments of the marking formulation, the gelatin can be type A gelatin, type B gelatin, hide gelatin, bone gelatin, or a combination thereof. In some embodiments, the gelatin can comprise 150 bloom gelatin, 200 bloom gelatin, 250 bloom gelatin, or a combination thereof.

[0077] In some embodiments of the marking formulation, the plasticizer can comprise glycerol, glycerol, sorbitol, sorbitol sorbitan solution, triacetin, polysorbate, or a combination thereof. In some embodiments, the plasticizer can be glycerol.

[0078] In some embodiments, the marking formulation does not contain titanium dioxide. In other embodiments, the marking formulation is substantially free of titanium dioxide. As described above, it has been found that using different metal oxides (e.g., iron oxide) instead of titanium dioxide or titanium oxide can achieve visible effects, such as color changes.

[0079] In some embodiments, the marking formulation may comprise water.

[0080] In one embodiment of the marking formulation, laser irradiation can be applied to the marking formulation at a wavelength of about 1000 nm to about 2200 nm. In some embodiments, laser irradiation can be applied using a fiber laser.

[0081] Any pharmaceutically active ingredient can be used for the purposes of the present invention. Suitable pharmaceutically active ingredients include, but are not limited to, analgesics and anti-inflammatory agents, antacids, anthelmintics, antiarrhythmics, antibacterials, anticoagulants, antidepressants, antidiabetics, antidiarrheals, antiepileptics, antifungals, antigouts, antihypertensives, antimalarials, antimigraines, antimuscarinics, antitumors and immunosuppressants, antiprotozoals, antirheumatic agents, antithyroid agents, antivirals, anxiolytics, sedatives, hypnotics and neuroleptics, beta-blockers, cardiac inotropes, corticosteroids, cough suppressants, cytotoxic agents, decongestants, diuretics, enzymes, antiparkinsonian agents, gastrointestinal agents, histamine receptor antagonists, lipid regulators, local anesthetics, neuromuscular agents, nitrates and antianginal agents, nutritional agents, opioid analgesics, oral vaccines, proteins, peptides and recombinant drugs, sex hormones and contraceptives, spermicides, stimulants and combinations thereof.

[0082] In some embodiments, the active pharmaceutical ingredient can be selected from, but is not limited to, the group consisting of dabigatran, dronedarone, ticagrelor, iloperidone, ivacaftor, midostaurine, asimadoline, beclomethasone, apremilast, sapacitabine, linsitinib, abiraterone, vitamin D analogs (e.g., calcifediol, calcitriol, paricalcitol, doxorcalciferol), COX-2 inhibitors (e.g., celecoxib, valdecoxib, rofecoxib), tacrolimus, testosterone, lubiprostone, pharmaceutically acceptable salts thereof, and combinations thereof.

[0083] According to certain embodiments, the active agent may comprise a lipid-lowering agent, including but not limited to statins (e.g., lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin, and pitavastatin), fibrates (e.g., clofibrate, ciprofibrate, bezafibrate, fenofibrate, and gemfibrozil), niacin, bile acid sequestrants, ezetimibe, lomitapide, phytosterols, and pharmaceutically acceptable salts, hydrates, solvates, and prodrugs thereof, mixtures of any of the foregoing, and the like.

[0084] Suitable nutraceutical actives may include, but are not limited to, 5-hydroxytryptophan, acetyl L-carnitine, alpha-lipoic acid, alpha-ketoglutarate, bee products, betaine hydrochloride, bovine cartilage, caffeine, cetearyl alcohol, charcoal, chitosan, choline, chondroitin sulfate, coenzyme Q10, collagen, colostrum, creatine, cyanocobalamin (vitamin B12), dimethylaminoethanol, fumaric acid, germanium sesquioxide, glandular products, glucosamine HCI, glucosamine sulfate, hydroxymethylbutyrate, immunoglobulins, lactic acid, L-carnitine, liver products, malic acid, anhydrous maltose, mannose (d-mannose), methylsulfonylmethane, phytosterols, picolinic acid, pyruvate, red yeast extract, S-adenosylmethionine, selenium yeast, shark cartilage, theobromine, vanadyl sulfate, and yeast.

[0085] Suitable nutritional supplement actives may include vitamins, minerals, fiber, fatty acids, amino acids, herbal supplements, or combinations thereof.

[0086] Suitable vitamin actives may include, but are not limited to, ascorbic acid (vitamin C), B vitamins, biotin, fat-soluble vitamins, folic acid, hydroxycitric acid, inositol, mineral ascorbate, mixed tocopherols, niacin (vitamin B3), orotic acid, para-aminobenzoic acid, pantothenate, pantothenic acid (vitamin B5), pyridoxine hydrochloride (vitamin B6), riboflavin (vitamin B2), synthetic vitamins, thiamine (vitamin B1), tocotrienols, vitamin A, vitamin D, vitamin E, vitamin F, vitamin K, vitamin oils, and oil-soluble vitamins.

[0087] Suitable herbal supplement actives may include, but are not limited to, arnica, bilberry, black cohosh, cat's claw, chamomile, echinacea, evening primrose oil, fenugreek, flaxseed, feverfew, garlic, ginger root, ginkgo biloba, ginseng, goldenrod, hawthorn, kava-kava, licorice, milk thistle, plantain, rauwolfia, senna, soy, St. John's wort, saw palmetto, turmeric, and valerian.

[0088] Mineral actives may include, but are not limited to, boron, calcium, chelated minerals, chlorides, chromium, coated minerals, cobalt, copper, dolomite, iodine, iron, magnesium, manganese, mineral premixes, mineral products, molybdenum, phosphorus, potassium, selenium, sodium, vanadium, malic acid, pyruvate, zinc, and other minerals.

[0089] Examples of other possible active agents include, but are not limited to, antihistamines (e.g., ranitidine, dimenhydrinate, diphenhydramine, chlorpheniramine, and dexchlorpheniramine maleate), nonsteroidal anti-inflammatory agents (e.g., aspirin, celecoxib, Cox-2 inhibitors, diclofenac, benoxaprofen, flurbiprofen, fenoprofen, flubufen, indoprofen, pirprofen, carprofen, oxaprozin, pramoprofen, muroprofen, suprofen, aminoprofen, fluprofen, bucloxic acid), acid), indomethacin, sulindac, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, meclofenamic acid, flufenamic acid, niflumic acid, tolfenamic acidacid, diflurisal, flufenisal, piroxicam, sudoxicam, isoxicam, aceclofenac, aloxiprin, azapropazone, benolate, bromfenac, carprofen, choline magnesium salicylate, diflunisal, etodolac c), etoricoxib, faislamine, fenbufen, fenoprofen, flurbiprofen, ibuprofen, indometacin, ketoprofen, ketorolac, lornoxicam, loxoprofen, meloxicam, mefenamic acid, metamizole, methyl salicylate, magnesium salicylate, nabumetone, naproxen, nimesulide, oxyphenbutazone, parecoxib, phenylbutazone, salicylate, sulindac, sulfinpyrazone, tenoxicam, tiaprofenic acid and mixtures thereof) and acetaminophen, antiemetics (e.g., metoclopramide, methylnaltrexone), antiepileptics (e.g., phenyloin, meprobamine, and nitrazepam), vasodilators (e.g., nifedipine, papaverine, diltiazem, and nicardipine), antitussives and expectorants (e.g., codeine phosphate), antiasthmatics (e.g., theophylline), antacids, antispasmodics (e.g., atropine, scopolamine), antidiabetics (e.g., insulin), diuretics (e.g., ethacrynic acid), and

[0013] The present invention also includes but is not limited to: antihistamines, analgesics, steroids, bendrofluthiazide, antihypertensives (e.g., propranolol, clonidine), antihypertensives (e.g., clonidine, methyldopa), bronchodilators (e.g., albuterol), steroids (e.g., hydrocortisone, triamcinolone, prednisone), antibiotics (e.g., tetracycline), antihemorrhoidal drugs, hypnotics, psychotropics, antidiarrheals, mucolytics, sedatives, decongestants (e.g., pseudoephedrine), laxatives, vitamins, stimulants (including appetite suppressants such as phenylpropanolamine), and cannabinoids, and pharmaceutically acceptable salts, hydrates, solvates, and prodrugs thereof.

[0090] The active agent may also be a benzodiazepine, a barbiturate, a stimulant, or a mixture thereof.The term "benzodiazepine" refers to benzodiazepines and drugs that are derivatives of benzodiazepines that are capable of depressing the central nervous system. Benzodiazepines include, but are not limited to, alprazolam, bromazepam, chlordiazepoxide, clorazepate, diazepam, estazolam, flurazepam, halazepam, ketazolam, lorazepam, nitrazepam, oxazepam, prazepam, quazepam, temazepam, triazolam, and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, and mixtures thereof. Benzodiazepine antagonists that may be used as active agents include, but are not limited to, flumazenil, and pharmaceutically acceptable salts, hydrates, solvates, and mixtures thereof.

[0091] The term "barbiturate" refers to a sedative-hypnotic drug derived from barbituric acid (2,4,6-trioxohexidine). Barbiturates include, but are not limited to, amobarbital, aprobarbotal, butabarbital, butalbital, methohexital, mephobarbital, metharbital, pentobarbital, phenobarbital, secobarbital, and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, and mixtures thereof. Barbiturate antagonists that can be used as active agents include, but are not limited to, amphetamine, and pharmaceutically acceptable salts, hydrates, solvates, and mixtures thereof.

[0092] The term "stimulant" includes, but is not limited to, amphetamines, such as dextroamphetamine resin complex, dextroamphetamine, methamphetamine, methylphenidate, and pharmaceutically acceptable salts, hydrates, solvates, and mixtures thereof. Stimulant antagonists that can be used as active agents include, but are not limited to, benzodiazepines, and pharmaceutically acceptable salts, hydrates, solvates, and mixtures thereof.

[0093] The dosage forms according to the present disclosure include various active agents and pharmaceutically acceptable salts thereof. Pharmaceutically acceptable salts include, but are not limited to, inorganic acid salts, such as hydrochlorides, hydrobromides, sulfates, phosphates, etc.; organic acid salts, such as formates, acetates, trifluoroacetates, maleates, tartrates, etc.; sulfonates, such as methanesulfonates, benzenesulfonates, p-toluenesulfonates, etc.; amino acid salts, such as arginine salts, aspartate salts, glutamate salts, etc.; and metal salts, such as sodium salts, potassium salts, cesium salts, etc.; alkaline earth metals, such as calcium salts, magnesium salts, etc.; organic amine salts, such as triethylamine salts, pyridinium salts, picoline salts, ethanolamine salts, triethanolamine salts, dicyclohexylamine salts, N,N'-dibenzylethylenediamine salts, etc.

[0094] Examples

[0095] Several sample soft gel capsules were prepared using various marker formulations that were tested using a fiber laser. In each example capsule, glycerin, purified water, and gelatin were combined with the marker formulation according to Table 1.

[0096] Table 1: Labeled formulations of capsules

[0097]

[0098] Capsules from Samples 1 to 4 were tested to see if they reacted when irradiated with a fiber laser at a wavelength of approximately 1064 nm. Each formulation was prepared with at least one iron oxide and without titanium dioxide. The results can be seen in the figure. All formulations containing iron oxide without titanium dioxide were found to react with the fiber laser, producing color changes and foaming.

[0099] While certain embodiments have been illustrated and described, it will be understood that changes and modifications may be made therein in accordance with ordinary skill in the art without departing from the technology in its broader aspects as defined in the following claims.

[0100] The embodiments illustratively described herein can be appropriately practiced in the absence of any one or more elements, one or more limitations not specifically disclosed herein. Thus, for example, the terms "comprise," "include," "contain," etc. should be broadly understood and are not limited. In addition, the terms and expressions employed herein have been used as terms of description rather than limitation, and are not intended to use such terms and expressions that do not include any equivalents of the features shown and described or parts thereof, but it should be recognized that various modifications within the scope of the claimed technology are possible. In addition, the phrase "essentially consisting of..." will be understood to include those elements specifically described and those additional elements that do not substantially affect the basic and novel characteristics of the claimed technology. The phrase "consisting of..." does not include any elements that are not specified.

[0101] With respect to the specific embodiments described in this application, the present disclosure is not limited. It will be apparent to those skilled in the art that many modifications and variations can be made without departing from its spirit and scope. In addition to those enumerated herein, functionally equivalent methods and compositions within the scope of the present disclosure will be apparent to those skilled in the art based on the foregoing description. Such modifications and variations are intended to fall within the scope of the appended claims. The present disclosure is limited only by the terms of the appended claims and the full scope of equivalents authorized by such claims. It should be understood that the present disclosure is not limited to specific methods, reagents, compounds or compositions, which can of course be changed. It should also be understood that the terms used herein are only used for the purpose of describing specific embodiments and are not intended to be limiting.

[0102] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0103] As will be understood by those skilled in the art, for any and all purposes, particularly with respect to providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any enumerated range is readily identifiable by sufficient description, and the same range can be decomposed into at least the same two, three, four, five, ten, etc. As a non-limiting example, each range discussed herein can be readily decomposed into a lower third, a middle third, and an upper third, etc. As will be understood by those skilled in the art, all language, such as "at most," "at least," "greater than," "less than," etc., includes the enumerated numbers and refers to a range that can subsequently be decomposed into subranges as discussed above. Ultimately, as will be understood by those skilled in the art, a range includes each individual member.

Claims

1. A soft gel capsule comprising: Filling material; as well as a shell composition, wherein the shell composition comprises a marking formulation comprising a marking component, wherein laser irradiation is applied to the soft gel capsule at a wavelength of about 1000 nm to about 2200 nm such that the marking component provides a visible effect.

2. The soft gel capsule of claim 1, wherein the marking component comprises a metal oxide.

3. The soft gel capsule of claim 2, wherein the marking formulation further comprises a plasticizer and gelatin.

4. The soft gel capsule according to claim 2 or 3, wherein the metal oxide comprises iron oxide.

5. The soft gel capsule according to claim 4, wherein the iron oxide is iron oxide red, iron oxide yellow, iron oxide brown, iron oxide black, iron oxide blue, iron oxide green or a combination thereof.

6. The soft gel capsule of any one of the preceding claims, wherein the marking formulation is substantially free of titanium dioxide.

7. The soft gel capsule of any one of the preceding claims, wherein the marking formulation does not contain titanium dioxide.

8. The soft gel capsule of any one of the preceding claims, wherein the laser irradiation is applied to the soft gel capsule at a wavelength of about 1200 nm to about 1800 nm.

9. The soft gel capsule according to any one of the preceding claims, wherein the laser irradiation is achieved using a fiber laser.

10. A method for labeling soft gel capsules, comprising: A soft gel capsule is irradiated with a laser, wherein the soft gel capsule comprises a shell composition and a fill material, and wherein the shell composition comprises a marking formulation having a marking component. The method of claim 10 , wherein the irradiating is performed using a wavelength above about 1000 nm.

12. The method of claim 10, wherein the irradiating is performed using a wavelength of about 1000 nm to about 2200 nm, about 1200 nm to about 2000 nm, or about 1500 nm to about 1800 nm.

13. The method of claim 10, wherein the irradiating is performed using a fiber laser.

14. The method of claim 10, wherein said marking component provides a visible effect after said irradiation of said soft gel capsule.

15. The method of claim 10, wherein the marking component is a metal oxide.

16. The method of claim 15, wherein the metal oxide comprises iron oxide.

17. The method of claim 16, wherein the iron oxide is iron oxide red, iron oxide yellow, iron oxide brown, iron oxide black, iron oxide blue, iron oxide green, or a combination thereof.

18. The method of any one of claims 10 to 17, wherein the marking formulation is substantially free of titanium dioxide.

19. A method according to any one of claims 10 to 18, wherein the marking formulation is free of titanium dioxide.

20. A marking formulation comprising: a marker component comprising a metal oxide; Plasticizers; as well as gelatin, wherein laser radiation is applied to the marking formulation at a wavelength of about 1000 nm to about 2200 nm such that the marking component provides a visible effect.

21. The marking formulation of claim 20, wherein the metal oxide comprises iron oxide.

22. The marking formulation of claim 21, wherein the iron oxide is red iron oxide, yellow iron oxide, brown iron oxide, black iron oxide, blue iron oxide, green iron oxide, or a combination thereof.

23. The marking formulation of claim 20, wherein the marking component is included in an amount of about 0.001 wt% to about 10 wt%, about 0.005 wt% to about 9 wt%, about 0.01 wt% to about 8 wt%, about 0.05 wt% to about 7 wt%, about 0.1 wt% to about 6 wt%, about 0.5 wt% to about 5 wt%, about 1 wt% to about 4 wt%, about 1.5 wt% to about 3 wt%, or about 2 wt% to about 2.5 wt%, based on the total weight of the marking formulation.

24. The marking formulation of claim 20, wherein the metal oxide is included in an amount of from about 1 gram to about 5 grams, from about 1.2 grams to about 4.5 grams, from about 1.4 grams to about 4 grams, from about 1.6 grams to about 3.5 grams, from about 1.8 grams to about 3 grams, or from about 2 grams to about 2.5 grams, based on 100 grams of the total weight of the marking formulation.

25. The marking formulation of claim 20, wherein the plasticizer is included in an amount of about 5 wt% to about 40 wt%, about 10 wt% to about 35 wt%, about 15 wt% to about 30 wt%, or about 20 wt% to about 25 wt%, based on the total weight of the marking formulation.

26. The marking formulation of claim 20, wherein the gelatin is included in an amount of about 20 wt% to about 70 wt%, about 25 wt% to about 65 wt%, about 30 wt% to about 60 wt%, about 35 wt% to about 55 wt%, or about 40 wt% to about 50 wt%, based on the total weight of the ink formulation.

27. The marking formulation of claim 20, wherein the gelatin comprises type A gelatin, type B gelatin, animal hide gelatin, bone gelatin, or a combination thereof.

28. The marking formulation of claim 20, wherein the gelatin comprises 150 bloom gelatin, 200 bloom gelatin, 250 bloom gelatin, or a combination thereof.

29. The marking formulation of claim 20, wherein the plasticizer comprises glycerol, glycerin, sorbitol, sorbitan solution, triacetin, polysorbate, or a combination thereof.

30. The marking formulation of claim 20, wherein the plasticizer comprises glycerin.

31. The marking formulation of any one of claims 20 to 30, wherein the marking formulation is substantially free of titanium dioxide.

32. The marking formulation of any one of claims 20 to 31 , wherein the marking formulation does not comprise titanium dioxide.

33. The marking formulation of any one of claims 20 to 32 further comprising water.

34. The marking formulation of any one of claims 20 to 33, wherein the laser irradiation is applied using a fiber laser.

Images