Coating composition and coated tablets

Abstract

A coating composition useful for coating tablets such as compressed tablets, caplets, pills, capsules, confectionery, or seeds contains an opacity amount of crospovidone having an average particle size of less than 10 μm. Crospovidone having an average particle size of less than 10 μm is used as an opacifying agent and white pigment in the coating of coated tablets, as a substitute for titanium dioxide.

Description

[Technical Field]

[0001] The present invention relates to coating compositions, particularly film coating compositions, coated tablets having the coating, and the use of crospovidone having an average particle size of less than 10 μm as an opacifying agent and white pigment in the coating. [Background technology]

[0002] Film coating is a process in which a substrate, such as a tablet, pellet, confectionery, or seed, is encased in a thin layer of polymer film-forming material. Film coating can be performed for a variety of reasons, including altering color for aesthetic purposes or branding, protecting materials from degradation due to environmental conditions such as moisture, oxygen, or light, modifying the release of active ingredients in pharmaceutical compositions, reducing bitterness, and / or reducing odor. Film coating is generally provided on tablets by using film-forming agents. Film coating of pharmaceutical tablets allows for an efficient, controlled, uniform, and reproducible coating.

[0003] Coating formulations typically contain opacifiers and white pigments to provide a specialized color coating. Without these components, the coating would remain translucent and opaque, leaving the substrate, such as the tablet core, visible. In the pharmaceutical industry, the standard white pigment is titanium dioxide, and the standard opacifier is talc.

[0004] In a May 2021 opinion published by the EFSA (European Food Safety Authority), titanium dioxide was no longer considered safe due to the uncertainty surrounding the genotoxicity of the nanoparticles it contains. A food ban was subsequently announced in January 2022. The pharmaceutical industry is currently unaffected, but pharmaceutical companies are beginning to restructure their formulations in preparation for a potential ban.

[0005] For example, various components such as calcium carbonate, magnesium oxide, and tricalcium phosphate have been evaluated by compounders. However, in addition to the fact that some of these excipients also contain nanoparticles or are not inert and tend to react with either polymers or active pharmaceutical ingredients (APIs), this process requires considerable effort. Color coating is insufficient compared to conventional formulations, and due to the high specific density of some of the pigments proposed as alternatives to titanium dioxide, pigment sedimentation in the coating dispersion is strongly noticeable. Consistently, a high level of coating is required, and insufficient process reliability is observed. To date, there is no solution available to compounders that matches the performance of titanium dioxide.

[0006] U.S. Patent Application Publication No. 2012 / 0164223 discloses a rapidly disintegrating solid coating formulation comprising a solid core coated with a film coating. The film coating comprises a rapidly water-soluble polyether-vinyl ester graft polymer that is completely or partially hydrolyzed and may contain 30% by weight or less of finely powdered crospovidone having an average particle size of 2 to 30 μm.

[0007] The article "Titanium Dioxide (E171 Grade) and the Search for Replacement Opacifiers and Colorants: Supplier Readiness Survey, Case Studies, and Regulatory Perspective" by B. Hancock et al. in the Journal of Pharmaceutical Sciences describes research on various TiO2 substitutes as opacifiers in solid dosage forms. Properties achieved using TiO2 as an opacifier, such as whiteness, have not been reproducible with the described substitutes. [Overview of the Initiative] [Means for solving the problem]

[0008] The present invention relates to a coating composition, particularly a film coating composition, having an average particle size of less than 10 μm and containing an opacity amount of crospovidone. The coating composition is useful for coating tablets such as compressed tablets, caplets, pills, capsules, confectionery, or seeds. Tablets include pharmaceutical tablets and nutritional supplements. [Brief explanation of the drawing]

[0009] [Figure 1] This graph shows the relationship between the coating level and the a value for coating formulations 1 to 7. [Figure 2] This graph shows the relationship between coating level and b-value for coating formulations 1-7. [Modes for carrying out the invention]

[0010] "Crospovidone" is a commonly used name in the pharmaceutical sector for water-insoluble crosslinked polyvinylpyrrolidone. Such substances are marketed, for example, as Kollidon® CL by BASF SE, Germany and as Polyplasdone® XL by International Specialty Products, USA. These substances have been used in powder form as tablet degraders or suspension stabilizers.

[0011] Crospovidone useful in this invention has an average particle size of less than 10 μm, for example less than 8 μm, for example 2 to 5 μm. Quite unexpectedly, it was found that these crospovidones can be used as substitutes for both talc and titanium dioxide in coatings. The incorporation of crospovidone was found to provide coating compositions with excellent whiteness, shielding power and coloring power.

[0012] Crospovidone with very small particle sizes obtained by micronization is crospovidone Kollidon® CL-M from BASF and Polyplasdone® INF-10 from International Specialty Products. Kollidon CL-M has a particle size D[4,3] of 3 μm to 10 μm. Crospovidone grades with even finer particle sizes may be useful, for example, for engraved tablets, and can reduce the risk of crosslinking, especially when a higher coating level is required. Kollidon CL-M is a pharmaceutical excipient. It is a standard excipient with regulatory freedom and priority for use in pharmacopoeia monographs and registered formulations.

[0013] The average particle size is described as the volume-average diameter, also known as the volume moment-average (De Brouckere mean diameter) D[4,3] in micrometers. D[4,3] is,

number

[0014] The opacity of crospovidone having an average particle size of less than 10 μm is the amount that imparts the desired opacity, preferably equivalent to that obtained with conventional coatings using inorganic materials such as titanium dioxide and talc. Generally, the opacity is 25% by weight or more, preferably 32% by weight or more or 40% by weight or more, and sometimes 50% by weight or more, relative to the solid content of the coating composition. Generally, the opacity is 85% by weight or less or 75% by weight or less, relative to the solid content of the coating composition. The actual opacity may depend on many factors, including the original color of the substrate, the desired color impression, and the pigment-binding ability of the film-forming agent.

[0015] In some cases, it may be desirable to impart a specific observable color, coloring or hue to the coated tablets. For this purpose, the coating composition may further comprise a colorant and / or pigment other than crospovidone. The combination of crospovidone with a colorant and / or pigment has been found to provide a colorless transparent and bright color tone.

[0016] The colorant and / or pigment can be any colorant and / or pigment used to produce a coating dispersion for pharmaceutical tablets and the like.

[0017] As used herein, the abbreviation "FD&C" is the abbreviation of "Food, Drug, and Cosmetic". FD&C colors are colors approved by the US "Federal Food, Drug, and Cosmetic Act" for use in foods, drugs, and cosmetics. Similarly, the abbreviation "D&C" is the abbreviation of "Drug and Cosmetic".

[0018] A "lake" is an insoluble substance that produces a pale color by dispersion. Lakes are produced by coloring an aluminum substrate using an FD&C dye.

[0019] Preferably, the colorant is selected from natural and synthetic colorants. For example, the colorant is - azo dyes, - FD&C colors such as FD&C Blue No.1 (Brilliant Blue FCF), FD&C Blue No.2 (Indigocarmine), FD&C Green No.3 (Fast Green FCF), FD&C Red No.3 (Erythrosine), FD&C Red No.4 (disodium salt), FD&C Red No.40 (Allura Red AC), FD&C Yellow No.5 (Tartrazine) and FD&C Yellow No.6 (Sunset Yellow FCF), - D&C colors such as D&C Green No.5 (Acid Green 25), D&C Green No.6 (Solvent Green 3), D&C Green No.8 (Solvent Green 7), D&C Orange No.4 (Acid Orange 7), D&C Orange No.5 (Acid Orange 11), D&C Red 17 (Sudan III), D&C Red 21 (Solvent Red 43), D&C Red 22 (Acid Red 87), D&C Red 27 (Solvent Red 48), D&C Red 28 (Acid Red 92), D&C Red 33 (Acid Red 33), D&C Yellow No.8 (Acid Yellow 73), D&C Yellow No.10 (Acid Yellow 3), D&C Yellow No.11 (Solvent Yellow 33), and External D&C Violet No.2 (Acid Violet 43), and - mixtures thereof are selected from water-soluble colorants such as these.

[0020] Preferably, the pigments are selected from natural and synthetic pigments. For example, the pigments are - red, yellow, and black iron oxides, - calcium carbonate, - magnesium carbonate, - zinc oxide, - calcined silica, - FD&C lakes such as FD&C Red No.40 aluminum lake (Allura Red), FD&C Blue No.1 aluminum lake (Brilliant Blue FCF), and FD&C Yellow No.5 aluminum lake (Tartrazine), - D&C rakes such as D&C Red No. 6 Barium Lake (Pigment Red 57), D&C Red No. 7 Calcium Lake (Pigment Red 57:1), D&C Red No. 27 Aluminum Lake (Solvent Red 48:2), D&C Red No. 28 Aluminum Lake (Pigment Red 174), D&C Red No. 30 Tal Lake (Vat Red 1), D&C Red No. 33 Aluminum Lake (Acid Red 33), D&C Violet No. 2 (Acid Violet 43), and D&C Yellow No. 10 Aluminum Lake (Pigment Yellow 115), - Mica-based pearlescent pigments, and - those mixtures Selected from.

[0021] The coating composition may contain colorants and / or pigments in an amount of 0.1 to 10% by weight relative to the solid content of the coating composition.

[0022] In preferred embodiments, the coating composition does not contain titanium dioxide, and preferably does not contain titanium dioxide and talc.

[0023] The advantage of crospovidone with an average particle size of less than 10 μm is its low specific density. Therefore, there is less sedimentation in preparation containers and piping, leading to high process reliability. Excellent tablet surface coverage and opacity are achieved, with superior results obtained at lower coating levels. At comparable levels, crospovidone with an average particle size of less than 10 μm performs better than all alternatives. Unlike talc, a natural product, batch-to-batch variability is expected to be reduced with crospovidone with an average particle size of less than 10 μm due to its synthetic nature.

[0024] The preparation of the coating formulation is simplified because a high-shear mixer is not required for particle deaggregation, dispersion handling is simplified in terms of reduced sedimentation tendency, and process reliability is improved for the same reason.

[0025] The coating technologies that can use the coating composition are not particularly limited. These include sugar coatings, organic solvent-based film coatings, aqueous film coatings, delayed-release coatings, and granular coating technologies. However, preferably, the coating composition is an aqueous film coating composition.

[0026] The coating composition may contain a film-forming agent, generally a polymeric film-forming agent. The polymeric film-forming agent is not particularly limited and may be selected from polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-vinyl acetate copolymer (copovidone), methylcellulose (MC), ethylcellulose (EC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (CMC sodium), polydextrose, starch, modified starch, polyvinyl alcohol (PVA), polyvinyl alcohol-based copolymers, polyvinyl acetate phthalate, or combinations thereof.

[0027] Preferred polyvinyl alcohol-based copolymers include acetate-polyalkylene ether graft copolymers that are completely or partially hydrolyzed after polymerization. Particularly preferred polymers are polyvinyl alcohol-polyether graft copolymers manufactured by Kollicoat® IR, BASF SE, Ludwigshafen, which correspond to monograph "Macrogol Poly(vinyl alcohol)Grafted Copolymer" in European Pharmacopoeia 6.7. This is a polyvinyl acetate-polyethylene glycol graft copolymer having vinyl acetate units with a degree of hydrolysis of 90-99 mol%, which is hydrolyzed after polymerization, as described in the European Pharmacopoeia as "a polymer having 75% polyvinyl alcohol and 25% polyethylene glycol in powder form". The viscosity as a 20% strength aqueous solution is 50-250 mPas. The molecular weight is 30,000-150,000 daltons, and the average molecular weight is preferably 45,000 g / mol.

[0028] Another preferred polyvinyl alcohol-based copolymer is Kollicoat® Protect, manufactured by BASF SE, Ludwigshafen, which is a mixture of Kollicoat® IR (polyvinyl alcohol (PVA)-polyethylene glycol (PEG) graft copolymer) and polyvinyl alcohol (PVA). Kollicoat® Protect and Kollicoat® IR are preferred polymers due to their high pigment loading capabilities.

[0029] The coating composition may contain polymers for improved drug release. Examples of such polymers include cellulose phthalate acetate, cellulose trimellitate acetate, hydroxypropyl methylcellulose phthalate, and methacrylate-based polymers.

[0030] Suitable methacrylate-based polymers include poly(butyl methacrylate, (2-dimethylaminoethyl) methacrylate, methyl methacrylate)) 1:2:1, poly(ethyl acrylate, methyl methacrylate) 2:1, poly(methacrylic acid, methyl methacrylate) 1:1, poly(methacrylic acid, ethyl acrylate) 1:1, poly(methacrylic acid, methyl methacrylate) 1:2, poly(methyl acrylate, methyl methacrylate, methacrylic acid) 7:3:1, poly(ethyl acrylate, methyl methacrylate, trimethylammoniumethyl methacrylate chloride) 1:2:0.2, poly(ethyl acrylate, methyl methacrylate, trimethylammoniumethyl methacrylate chloride) 1:2:0.1, and poly(methyl methacrylate-diethylaminoethyl methacrylate) 6:4.

[0031] The amount of film-forming agent used in the composition may be in the range of 20% to 75% by weight, more preferably 24% to 42% by weight.

[0032] The coating composition may contain wetting agents, waxy components, plasticizers, flow enhancers, flavoring agents, sweeteners, additional polymers, and / or other pharmaceutically acceptable excipients.

[0033] The compositions of the present invention may contain plasticizers. As used herein, the term “plasticizer” refers to a compound having plasticizing properties useful for forming a complete film. Plasticizers may be used alone or in combination with other plasticizers. Plasticizers may be selected from phthalates, phosphates, citrates, stearates, sebacates, oleates, and adipates, as well as other esters, oils, glycerols, and glycols. Preferably, plasticizers are selected from ethyl phthalate, methyl phthalate, dipropyl phthalate, diethyl phthalate, glycerin, polyethylene glycol (PEG), triethyl citrate (TEC), dibutyl sebacate (DBS), diethyl phthalate (DEP), dibutyl phthalate (DBP), and triacetin. More preferably, plasticizers are selected from diethyl phthalate, triethyl citrate, dibutyl phthalate, and combinations thereof.

[0034] The amount of plasticizer used in the composition may be in the range of 5% to 20% by weight, more preferably in the range of 15% to 7% by weight.

[0035] The compositions of the present invention may include a waxy component or a combination of waxy components. As used herein, the term "waxy" refers to a substance having hydrophobic activity. The waxy component may be selected from fatty acids, glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, magnesium stearate, sorbitan esters, stearic acid, palmitic acid, polyoxyethylene alkyl ethers, lauroyl polyoxyglycerides and stearoyl polyoxyglycerides, cetostearyl alcohol, cetyl alcohol, serosine, propylene glycol monostearate, sorbitan tristearate, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oil, carnauba wax, microcrystalline wax, sodium dioctyl sulfosuccinate, ethylene glycol stearate, glyceryl monooleate, lanolin, myristic acid, peteractam / lanolin alcohol and stearate derivatives. The amount of waxy component used in the composition may be in the range of 0.1% to 10% by weight, more preferably in the range of 1% to 7% by weight.

[0036] The wetting agent used in the composition of the present invention may be selected from ammonium lauryl sulfate, sodium lauryl sulfate, polysorbate-20, polysorbate-40, polysorbate-60, polysorbate-80, and more preferably polysorbate-80.

[0037] The amount of wetting agent used in the composition may be in the range of 0.1% to 4% by weight, more preferably 0.5% to 3% by weight.

[0038] The compositions of the present invention may include a flow accelerator. As used herein, the term “flow accelerator” refers to a compound that increases the flow of a dry powder. The flow accelerator may be selected from magnesium stearate, Aerosil® (colloidal silicon dioxide), starch, hydrophobic colloidal silica, magnesium oxide, magnesium silicate, and magnesium trisilicate.

[0039] The amount of flow promoter used in the composition may be in the range of 0.1% to 10% by weight, more preferably 2% to 7% by weight.

[0040] The preparation process for the coating composition of the present invention involves combining the components of the composition, which include a film-forming agent, a plasticizer, and an optional component. These combinations of components can be achieved by several processes, such as heating, stirring, and mixing, to obtain a homogeneous dispersion. After the initial mixing, crospovidone and other pharmaceutically acceptable excipients having an average particle size of less than 10 μm may be added to obtain the composition of the present invention. The coating composition of the present invention has good adhesion properties, particularly good film-forming properties.

[0041] The coating may be applied by a spray coating process commonly used to coat orally ingestible substrates. The amount of coating applied will depend on several factors, including the properties and functionality of the coating, the substrate being coated, and the equipment used to apply the coating. The coating compositions of the present invention may also be suitable for large-volume batch processes and continuous coating operations.

[0042] In a further embodiment, the present invention is (a) Tablet core and (b) A coating having an average particle size of less than 10 μm, containing an opacity amount of crospovidone and Regarding coated tablets, including those containing [specific components].

[0043] Generally, the amount of opacity is 25% by weight or more of the total weight of the coating, preferably 32% by weight or more, or 40% by weight or more, and in some cases 50% by weight or more.

[0044] Preferably, the surface coverage of the crospovidone-coated tablets is 1 mg / cm². 2 Preferably 2 mg / cm³ 2 More preferably 3 mg / cm³ 2That concludes the explanation. Generally, the surface coverage of crospovidone-coated tablets is 9 mg / cm². 2 The following applies: Surface coverage is calculated as the percentage of crospovidone in the coating × the geometric surface area of ​​the tablet [cm²]. 2 This is intended to mean the amount of applied coating per unit [in mg as solids].

[0045] Coated tablets may contain a coating composition comprising a coloring agent and / or a pigment.

[0046] The tablet core may contain pharmaceuticals, dietary supplements and health supplements, and any other orally ingestible cores recognized in the art. Generally, the tablet core contains at least one pharmaceutically active ingredient.

[0047] Suitable pharmaceutically effective ingredients that may be included in the tablet core include, but are not limited to, adrenergic blockers, acetylcholinesterase inhibitors, analgesics or antipyretics, angiotensin modulators, anthelmintics, anxiolytics, antibacterial agents, antibiotics, anticoagulants, anticonvulsants, antidepressants, antifungal agents, antihistamines, antimalarial agents, antibacterial agents, antipsychotics, antiviral agents, hypoglycemic agents, calcium channel modulators, diuretics, erectile dysfunction agents, gastric acid secretion inhibitors, histamine H2 receptor antagonists, steroid type II 5α-reductase inhibitors, lipid modulators, selective HI receptor antagonists, vasodilators, and vitamins.

[0048] The coating composition is applicable to tablet cores containing one or more acidic pharmaceutically active ingredients. Pharmaceutical ingredients with pKa values ​​between 1 and 8 are considered acidic pharmaceutically active ingredients. These acidic pharmaceutically active ingredients may cause incompatibility with coatings containing basic pigments such as carbonates. Crospovidone with an average particle size of less than 10 μm does not experience such incompatibility.

[0049] The core may contain a tabletting excipient. Examples of tabletting excipients include fillers such as lactose, cellulose powder, calcium diphosphate, microcrystalline cellulose, sugar alcohols such as mannitol, sorbitol and starch, tablet disintegrating substances such as starch (derivatives), croscarmellose, crospovidone, carboxymethyl cellulose (CMC), lubricants such as stearic acid and magnesium stearate, flow promoters such as silicon dioxide (Aerosil) or mixtures thereof.

[0050] In a further aspect, the present invention relates to the use of crospovidone having an average particle size of less than 10 μm as an opacifying agent and a white pigment in the coating of coated tablets, particularly the film coating of film-coated tablets.

Example

[0051] Tablet cores were produced as follows: A powder mixture was obtained by mixing the components shown in Table 1 below. The mixture was tableted using a tableting machine (9 mm concave punch, upper compression force: 9.4 kN). The average tablet weight was adjusted to 322.9 mg. The average surface of each tablet was 2.14 cm 2 was.

[0052]

Table 1

[0053] The tablet cores were further processed in a perforated drum coater at an inlet air temperature of 55 °C, a bed temperature of 37 °C, an inlet air volume of 280 cm 3 / h, a spraying rate of 15 g / min, a spraying pressure of 1 bar and a pattern pressure of 1 bar to obtain film tablets.

[0054] Coating formulations 1 to 7 according to Table 2 below were studied.

[0055]

Table 2

[0056] The coating was applied as a 20% dispersion. The tablets were divided into 1-10 (12) mg / cm³. 2 The coating was applied within the specified range.

[0057] Nimodipine is a yellow API, and the tablets are correspondingly yellow. The yellowness of the film-coated tablets was evaluated by measuring the color value related to the L*a*b color model using a DataColor 400 spectrophotometer.

[0058] The graph shows the color change from yellow to white as the coating level increases. Sample 3 (85 wt% Kollidon CL-M) and Sample 4 (75 wt% Kollidon CL-M) perform better than Reference 2 (30.5 wt% talc and 3.5 wt% TiO2). In Sample 3, chalking and coating defects were observed after exceeding the maximum pigment load. For less demanding purposes, lower concentrations of clospidone with an average particle size of less than 10 μm may suffice.

[0059] Shielding capacity evaluation In this example, the shielding power of a coating composition is evaluated by coating blue mock tablets with various amounts of the coating composition.

[0060] Tablet cores of 100% by weight of Kollitab DC 87L were prepared as described above. The tablet cores were subcoated with a coating formulation of 1% by weight of FD&C Blue and 99% by weight of Kollicoat IR. The subcoating was applied as a 20% dispersion. The tablet cores were subcoated until a 5% weight increase was achieved to obtain blue subcoated tablets.

[0061] Subsequently, the blue sub-coated tablets were top-coated using coating formulations 4 and 8* from Table 2. The top coating was applied as a 20% dispersion. The tablets were administered at a concentration of 4-24 mg / cm². 2(Coating composition 4) and 4-28 mg / cm² 2 The top coating was applied at a coating level within the range of (coating composition 8*). The top coating was performed using a GEA CosiGma Coater at a drum speed of 100 rpm, an inlet air temperature of 70°C, an air knife temperature of 75°C, a spray rate of 110 g / min, a spray pressure of 1.5 bar, and a pattern pressure of 1.3 bar.

[0062] The obtained top-coated tablets were studied in terms of their ΔE values. ΔE represents the distance between two colors in the CIE-Lab system. It is calculated from the coordinates of the two color positions. Using the ΔE value, a numerical value can be assigned to the difference between two colors (as perceived by the human eye).

number

[0063] "Ideal white" has an "L value" of 100, an "a value" of 0, and a "b value" of 0. "Ideal black" has an "L value" of 0, an "a value" of 0, and a "b value" of 0.

[0064] The obtained ΔE values ​​are shown in Table 3.

[0065] [Table 3]

[0066] Tablets top-coated with coating composition 4 of the present invention have a smaller deviation from ideal white (at the same coating level) compared to tablets top-coated with reference coating composition 8*. The visible appearance of tablets top-coated with the coating composition of the present invention is closer to "ideal white" at lower coating levels compared to tablets top-coated with the reference coating composition.

[0067] Coating containing colorants / pigments in addition to crospovidone The coloration of Kollicoat IR (film-forming agent) based Kollidon CL-M coating was tested on Ludipress LCE tablets.

[0068] SilentCrusher M (available from Heidolph) was used to disperse the pigment.

[0069] Tablet cores having the components shown in Table 4 below were manufactured as described above. The tablet cores had a load capacity of 2.78 N / mm². 2 It had a tensile strength of 5.05 mm and a height of 5.05 mm.

[0070] [Table 4]

[0071] Coating formulations 9 and 10 were studied according to Table 5 below.

[0072] [Table 5]

[0073] For coating preparation, Kollicoat IR was dissolved in 70% of the total volume of water. Then, Kollidon CL-M was added, and the mixture was stirred for 1 hour. Iron oxide (E172) was dispersed in the remaining water (30% of the total volume) at 10,000 rpm for 10 minutes. The resulting suspension was added to the Kollicoat IR / Kollidon CL-M suspension.

[0074] The coating suspensions in Table 5 were applied to the tablet cores in Table 4 until a 4% weight increase was achieved. Samples were taken at 1%, 2%, 3%, and 4% weight increases (1% = 95g of suspension). Good coloration was achieved at weight increases of 3% or more.

[0075] Coating formulations 11-19 were studied according to Table 6 below.

[0076] [Table 6]

[0077] For coating preparation, Kollicoat IR was dissolved in water. A coloring agent and Kollidon CL-M were added, and the mixture was stirred for 1 hour.

[0078] The coating suspensions in Table 6 were applied to the tablet cores in Table 4 until a 4% weight increase was achieved (4% = 380g suspension). Good, strong coloration was achieved.

Claims

1. A coating composition containing an opacity-enhancing amount of crospovidone having an average particle size of less than 10 μm.

2. The coating composition according to claim 1, wherein the opacity amount is 25% by weight or more, preferably 32% by weight or more, or 40% by weight or more, relative to the solid content of the coating composition.

3. A coating composition according to claim 1 or 2, comprising a coloring agent and / or a pigment.

4. A coating composition according to any one of claims 1 to 3, which does not contain titanium dioxide.

5. A coating composition according to any one of claims 1 to 4, comprising a polymer film-forming agent.

6. The coating composition according to claim 5, wherein the polymer film-forming agent is selected from polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-vinyl acetate copolymer (copovidone), methylcellulose (MC), ethylcellulose (EC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (CMC sodium), polydextrose, starch, modified starch, polyvinyl alcohol (PVA), polyvinyl alcohol-based copolymer, polyvinyl acetate phthalate, cellulose phthalate acetate, cellulose trimellitate acetate, hydroxypropyl methylcellulose phthalate, methacrylate-based polymer, or a combination thereof.

7. (a) Tablet core and (b) A coating having an average particle size of less than 10 μm and containing an opacity amount of crospovidone Coated tablets containing [a specific ingredient / material].

8. The coating tablet according to claim 7, wherein the amount of opacity is 25% by weight or more, preferably 32% by weight or more, or 40% by weight or more, of the total weight of the coating.

9. The surface coverage of the coated tablet using crospovidone is 1 mg / cm². ２ Preferably 2 mg / cm² ２ More specifically, 3 mg / cm³ ２ The coated tablet according to claim 7 or 8.

10. The coating composition comprises a colorant and / or a pigment, as described in any one of claims 7 to 9.

11. The coating is a coated tablet according to any one of claims 7 to 10, wherein the coating does not contain titanium dioxide.

12. The coated tablet according to claim 11, wherein the coating further does not contain talc.

13. The coated tablet according to any one of claims 7 to 12, wherein the tablet core contains at least one pharmaceutically effective ingredient.

14. Use of crospovidone having an average particle size of less than 10 μm as an opacifying agent and white pigment in the coating of coated tablets.

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