Coating composition and coated tablet

Abstract

A coating composition comprises a) a polymeric film-former, and b) 20 wt.-% or more, relative to the solids content of the coating composition, of a gloss agent being sodium stearyl fumarate. The coating composition comprising sodium stearyl fumarate results in a coating with improved gloss.5

Description

[0001] Coating Composition and Coated Tablet

[0002] The present invention relates to a coating composition, a coated tablet, and a method for preparing the coating composition.

[0003] Film coating is a process in which a substrate, such as a tablet, a pellet, a confectionary or a seed, is enveloped by a thin layer of polymeric film forming material. Film coating of solid dosage forms such as tablets is a technique which has been widely used for years in modern drug formulation and tablet production. Film coating may be carried out for a wide variety of reasons such as modifying a tablet's appearance, i.e. its optical properties such as gloss; changing the color for aesthetic purposes or branding; protecting the material from degradation due to environmental conditions such as moisture, oxygen or light; modifying the release of the active ingredient of a pharmaceutical composition; alleviating bitterness; and / or reducing release of an odor. The film coating is generally provided on a tablet by using a film former. Film coating of pharmaceutical tablets allows efficient, controlled, uniform and reproducible coats.

[0004] Important requirements to be met by a film coating are that it is not tacky, adheres well to the substrate to be coated, is stable to mechanical stress and shows no fissuring on storage, and shows an excellent smoothness and gloss. In addition, it should be possible for the polymers of the film-coating solution to be prepared and dissolved in a solvent (such as water) quickly and easily. The film-coating solution should moreover have a low viscosity at a sufficiently high solids content in order to ensure good processing.

[0005] Film-forming polymers have been employed for years for coating tablets, for example cellulose derivatives such as hydroxypropylcellulose, hydroxypropylmethylcellulose, methacrylic acid copolymers or else polyvinyl alcohol copolymers. The use of polymers such as polyethylene glycol and polyvinylpyrrolidone as film-forming components in coating compositions is also known.

[0006] Known polymer compositions have the disadvantage when applied to a substrate to be coated, e.g. to a tablet core, of frequently producing a dull, non-glossy, unattractive and rough surface whose color is not matching the color of coatings comprising conventionally used white pigments and opacifiers. In order to confer on such substrates a more attractive, glossy appearance, it is intended to coat substrates with a glossy film.

[0007] Sugar coated tablets, and particularly those which have been polished, for example, with a top coat of carnauba wax, may typically possess higher surface gloss than film coated tablets, however the sugar coating process is highly time consuming and costly, and the coatings thus prepared can disadvantageously retard the dissolution of the dosage forms.

[0008] US 11 ,191 ,731 B2 relates to a film coating composition comprising a) about 3% to about 60% by weight hydroxypropyl methyl cellulose (HPMC); b) about 3% to about 25% by weight of polyol; c) a plasticizing agent comprising medium chain triglycerides; and d) about 15% to about 60% by weight of an opacifying agent. The coating composition may comprise a lubricant which may, inter alia, be selected from sodium stearyl fumarate. A gloss-increasing effect of the film coating is not described.

[0009] US 2011 / 0117142 discloses a polymeric composition for coating solid substrates consisting of a) 0.5-90% by weight of polyethylene glycol with a weight-average molecular weight in the range from 1500 to 20 000 g / mol, b) 0.5-20% by weight of a water-soluble polyvinylpyrrolidone with a Fikentscher K value in the range from 12 to 90, c) 0-95% by weight of a solvent (L), and d) 0-70% by weight of one or more non-polymeric aids. US 2011 / 0117142 aims at improving the gloss of substrates.

[0010] It is an object of the present invention to provide, and apply to the substrate, a coating composition which produces or improves the gloss. It should be possible to carry out the process for applying the composition easily and preferably with an aqueous solution.

[0011] The object is solved by a coating composition comprising a) a polymeric film-former, and b) 20 wt.-% or more, relative to the solids content of the coating composition, of a gloss agent being sodium stearyl fumarate.

[0012] It has surprisingly been found that the coating composition of the invention comprising sodium stearyl fumarate results in a coating with improved gloss. Furthermore, the inventive coating composition has an opacifying performance in film-coating equal to the performance of talc or other common opacifiers such as kaolin.

[0013] In comparison to talc, using sodium stearyl fumarate in coating compositions is advantageous as the processing characteristics improve. Sodium stearyl fumarate particles are smaller and have a lower specific density resulting in reduced sedimentation. This in turn advantageously results in a more robust and more reliable filmcoating process. Furthermore, the coatings obtained from the inventive coating compositions have a very similar color compared to the coatings comprising the conventionally used white pigments and opacifiers, i.e. the inventive coating compositions allow for color matching. i-former

[0014] The inventive coating composition comprises a polymeric film-former a). The polymeric film-former is not subject to particular restrictions. It may be selected from polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-vinyl acetate copolymer (copovidone), methylcellulose (MC), ethyl cellulose (EC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (sodium CMC), polydextrose, starch, modified starch, polyvinyl alcohol (PVA), copolymers based on polyvinyl alcohol, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, methacrylate-based polymers, polyethylene glycols, graft polymers based on polyethers, and combinations thereof.

[0015] Preferred polymeric film-formers are selected from copolymers based on polyvinyl alcohol, methacrylate-based polymers, copolymers based on polyethylene glycol, and combinations thereof.

[0016] Preferred copolymers based on polyvinyl alcohol include acetate-polyalkylene ether graft copolymer completely or partially hydrolyzed after the polymerization. A particularly preferred polymer is Kollicoat® IR, a polyvinyl alcohol-polyether graft copolymer, available from BASF SE, Ludwigshafen, which corresponds to the monograph "Macrogol Poly(vinyl alcohol) Grafted Copolymer” in European Pharmacopeia 6.7. This is a polyvinyl acetate-polyethylene glycol graft copolymer with vinyl acetate units hydrolyzed after the polymerization and having a degree of hydrolysis of from 90 to 99 mol-%, stated in the European Pharmacopeia as "Polymer with 75% polyvinyl alcohol and 25% polyethylene glycol in powder form”. The viscosity as 20% strength aqueous solution is between 50 and 250 mPas. The molecular weight is between 30 000 and 150 000 daltons, the average molecular weight is preferably 45 000 g / mol.

[0017] Preferred methacrylate-based polymers include co-polymers comprising methyl methacrylate (MMA) and diethylaminoehtylmethacrylate (DEAEMA), e.g. in the ratio 6:4. Particularly preferred methacrylate-based polymers are those from the Kollicoat® Smartseal series, available from BASF SE, Ludwigshafen.

[0018] Preferred graft polymers based on polyethers include copolymers obtained by free-radical polymerization of a mixture of i) 30 to 80% by weight of N-vinyllactam. ii) 10 to 50% by weight of vinyl acetate, and iii) 10 to 50% by weight of a polyether, with the proviso that the total of components i), ii) and iii) equals 100% by weight. Such copolymers and their preparation are described in detail in WO 2007 / 051743.

[0019] Specifically, the graft polymers based on polyethers may be polyvinyl caprolactam-polyvinyl acetatepolyethylene glycol graft copolymers (PCA-PVA-PEG). They are commercially available from BASF SE, Ludwigshafen as Soluplus®.

[0020] The coating composition may contain polymers for modified drug release. Such polymers include cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, methacrylate-based polymers and the like. 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, trimethylammonioethyl methacrylate chloride) 1 : 2 : 0.2, poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1 : 2 : 0.1 , poly(methyl methacrylate-diethylaminoethyl methacrylate) 6 : 4.

[0021] The amount of polymeric film-former in the coating composition may suitably be less than 80 wt.-%, relative to the solids content of the coating composition. For example, the amount of polymeric film-former in the coating composition may be in the range of from 20 to 75 wt.-%, preferably 20 to 50 wt.-%, relative to the solids content of the coating composition. b) Gloss agent

[0022] The inventive coating composition comprises a gloss agent b). The gloss agent is sodium stearyl fumarate. It has surprisingly been found in the context of the present invention that the presence of sodium stearyl fumarate allows for providing coating compositions yielding coatings with improved gloss.

[0023] The inventive coating composition comprises 20 wt.-% or more, relative to the solids content of the coating composition, of the gloss agent being sodium stearyl fumarate. Preferably, the coating composition comprises 40 wt.-% or more of the gloss agent, relative to the solids content of the coating composition. Amounts of 40 wt.-% or more of the gloss agent result in coating compositions yielding coatings with a further improved gloss.

[0024] The coating composition may comprise the gloss agent in an amount in the range of from 20 to 80 wt.-%, preferably 20 to 72 wt.-%, more preferably 40 to 60 wt.-%.

[0025] Surfactant

[0026] In order to facilitate dispersion of the gloss agent in the coating composition, the coating composition may comprise at least one surfactant.

[0027] The surfactant is not particularly limited and may be selected from ionic and nonionic surfactants. The surfactant may be a low molecular compound or polymeric. The polymeric film-former a) as described above may concurrently act as polymeric film-former and surfactant, such as polyvinyl caprolactam-polyvinyl acetatepolyethylene glycol graft copolymers (PCA-PVA-PEG). Suitable surfactants are selected from sodium lauryl sulfate, sorbitan fatty acid esters, ethoxylated sorbitan fatty acid esters, ethoxylated esters of hydrogenated castor oil, ethoxylated fatty acid esters, sodium dioctylsulfosuccinate, graft polymers based on polyethylene glycol and poloxamers.

[0028] Specifically, the surfactant may be selected from sodium lauryl sulfate (Kolliphor SLS, available from BASF SE), graft polymers based on polyethylene glycol (Soluplus®, available from BASF SE), Kolliphor® HS 15 (Macrogol 15 Hydroxystearate), Tween® 80, polyoxyethylated fatty acid derivatives such as Kolliphor® RH 40 (polyoxyl 40 Hydrogenated Castor Oil, USP), Kolliphor® EL (Polyoxyl 35 Castor Oil, USP), poloxamers, and docusate sodium.

[0029] Special preference is given to sodium lauryl sulfate (Kolliphor SLS, available from BASF SE) and graft polymers based on polyethylene glycol (Soluplus®, available from BASF SE).

[0030] Non-polymeric surfactants may be used in the coating composition in an amount in the range of 0.5 to 5 wt.-%, preferably 1 to 3 wt.-%, relative to the solids content of the coating composition.

[0031] Polymeric surfactants, in particular those which simultaneously act as film-formers, may be used in the coating composition in an amount in the range of 40 to 80 wt.-%, preferably 50 to 60 wt.-%, relative to the solids content of the coating composition.

[0032] Further components

[0033] The coating composition may additionally comprise at least one of an opacifier, a colorant and a pigment.

[0034] A suitable opacifier may be crospovidone. "Crospovidone” is a name customary in the pharmaceutical sector for water-insolubly crosslinked polyvinylpyrrolidone. Such substances are commercially available, for example, as Kollidon® CL, from BASF SE, Germany, and also as Polyplasdone® XL from International Speciality Products, USA.

[0035] The crospovidones may have an average particle size of less than 10 pm, for example less than 8 pm, e.g., 2 to 5 pm. Crospovidone can be used as a substitute for both talc and titanium dioxide in coatings.

[0036] Crospovidones having very small particle sizes obtained by micronization are the crospovidones Kollidon® CL- M from BASF and Polyplasdone® INF-10 from International Speciality Products. Kollidon® CL-M has a particle size D[4,3] of 3 to 10 pm. Crospovidone grades with an even finer particle size could be useful, e.g., for engraved tablets and could reduce the risk of bridging, particularly when higher coating levels are required. Kollidon® CL-M is a pharmaceutical excipient. It is a standard excipient with regulatory freedom, pharmacopoeia monographs and precedence of use in registered drug products. The average particle sizes is stated as volume mean diameter, also referred to as volume moment mean (De Brouckere mean diameter) D[4,3] in micrometers. D[4,3] is defined as where n; is the frequency of occurrence of particles in size class i, having a mean Di diameter. The size distribution is suitably determined by means of laser defractometry using a Malvern Mastersizer X at a compressed-air atomization of 2 bar.

[0037] The coating composition may comprise crospovidon in an amount of up to 50 wt.-%, preferably up to 40 wt.-%, or up to 30 wt.-% or more, relative to the solids content of the coating composition.

[0038] In some cases, it may be desirable to impart a specific observable color, coloration or hue to the coated tablet. To this end, the coating composition may additionally comprise a colorant and / or a pigment other than crospovidone. The combination of crospovidone with a colorant and / or a pigment provides clear and bright color tones.

[0039] The colorant and / or pigment may be any colorant and / or pigment used in making coating dispersions for pharmaceutical tablets and the like.

[0040] Herein, the abbreviation "FD&C” is short for "Food, Drug, and Cosmetic”. FD&C colors are colors approved by the United States "Federal Food, Drug, and Cosmetic Act” for food, drugs and cosmetics. Analogously, the abbreviation "D&C” is short for "Drug, and Cosmetic”.

[0041] A "lake” is an insoluble material that tints by dispersion. Lakes are produced by coloring aluminum salt substrates using FD&C dyes.

[0042] Suitably, the colorant is selected from natural and synthetic colorants. For example, the colorant is selected from water-soluble colorants such as

[0043] - azo dyes;

[0044] - FD&C colors such as FD&C Blue No. 1 (Brilliant blue FCF), FD&C Blue No. 2 (Indigo carmine), 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);

[0045] - 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);

[0046] - and mixtures thereof.

[0047] Suitably, the pigment is selected from natural and synthetic pigments. For example, the pigment is selected from

[0048] - red, yellow, brown and black iron oxides;

[0049] - calcium carbonate;

[0050] - magnesium carbonate;

[0051] - zinc oxide;

[0052] - pyrogenic silica;

[0053] - 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);

[0054] - D&C lakes 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 Talc 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);

[0055] - mica based pearlescent pigments;

[0056] - and mixtures thereof.

[0057] The coating composition may comprise the colorant and / or pigment in an amount of 0.01 to 10 wt.-%, relative to the solids content of the coating composition.

[0058] In preferred embodiments, the coating composition is free of titanium dioxide, preferably free of titanium dioxide and talc.

[0059] The coating composition may additionally contain a plasticizer, a wetting agent, a waxy component, a glidant, a flavoring agent, a sweetening agent, an additional polymer and / or other pharmaceutically acceptable excipients.

[0060] The term "plasticizer” as used herein refers to compounds having plasticizing properties which are useful to form an integer film. The plasticizer may be used alone or in combination with other plasticizer(s). The plasticizer may be selected from phthalate esters; phosphate esters; other esters like citrates, stearates, sebacates, oleates, and adipates; oils, glycerol, and glycols.

[0061] Preferably, the plasticizer is selected from ethyl phthalate, methyl phthalate, dipropyl phthalate, diethyl phthalate, glycerine, polyethylene glycol (PEG), triethyl citrate (TEC), dibutyl sebacate (DBS), diethyl phthalate (DEP), dibutyl phthalate (DBP), triacetin. More preferably, the plasticizer is selected from dibutyl sebacate, diethyl phthalate, triethyl citrate, dibutyl phthalate, and combinations thereof. Dibutyl sebacate is especially preferred.

[0062] The coating composition may additionally contain a wetting agent. The wetting agent may be selected from ammonium lauryl sulfate, sodium lauryl sulfate, polysorbate-20, polysorbate-40, polysorbate-60, polysorbate- 80, preferably polysorbate-80.

[0063] The amount of wetting agent in the coating composition may be in the range of from 0.5 to 5 wt.-%, preferably 1 to 3 wt.-%, relative to the solids content of the coating composition.

[0064] The coating composition may additionally contain a waxy component or a combination of waxy components. The term "waxy” as used herein refers to the substance having hydrophobic activity. The waxy component may be selected from fatty acids, glyceryl mono-stearate, glyceryl behenate, glyceryl palmitostearate, magnesium stearate, sorbitan esters, stearic acid, palmitic acid, polyoxyethylene alkyl ethers, lauroyl polyoxyl glycerides and stearoyl polyoxyl glycerides, cetostearyl alcohol, cetyl alcohol, cerosin, propylene glycol monostearate, sorbitan tristearate, sodium stearyl fumarate, stearyl alcohol, hydrogenated vegetable oil, carnauba wax, microcrystalline wax, dioctyl sodium sulfosuccinate, ethylene glycol stearates, glyceryl monooleate, lanolin, myristic acid, petrolatum / lanolin alcohols, and derivatives of stearate.

[0065] The amount of waxy component in the coating composition may be in the range of from 5 to 30 wt.-%, preferably 10 to 20 wt.-%, relative to the solids content of the coating composition.

[0066] Coated tablet

[0067] The invention further relates to a coated tablet comprising

[0068] 1) a tablet core, and

[0069] 2) a coating comprising a) a polymeric film-former, and b) 20 wt.-% or more, relative to the solids content of the coating, of a gloss agent being sodium stearyl fumarate.

[0070] Suitably, the surface coverage of the coated tablet with the coating is 6 mg / cm2or more, preferably 12 mg / cm2or more, more preferably 14 mg / cm2or more, in particular 24 mg / cm2or more. Generally, the surface coverage of the coated tablet with the coating is 36 mg / cm2or less. The surface coverage is intended to mean the amount of coating [in mg as solids] applied per geometrical surface area of the tablet [in cm2].

[0071] The coating may additionally comprise at least one of a surfactant. Regarding the surfactant, the definitions and embodiments as outlined above regarding the coating composition analogously apply for the coating. The coating may additionally comprise at least one of an opacifier, a colorant and a pigment. Regarding the opacifier, colorant and / or pigment, the definitions and embodiments as outlined above regarding the coating composition analogously apply for the coating.

[0072] The tablet core may include pharmaceuticals, nutraceuticals and dietary supplements as well as any other art- recognized orally ingestible core. Generally, the tablet core comprises at least one pharmaceutically active ingredient.

[0073] Suitable pharmaceutically active ingredient that may be comprised in the tablet core include, but are not limited to: adrenergic blocking agents; acetyl-cholinesterase inhibitors; analgesic or antipyretics; angiotensin modulators; anthelmintic agents; anti-anxiety agents; antibacterial agents; antibiotics; anticoagulants; anticonvulsant agents; antidepressants; antifungal agents; antihistamines; antimalarial agents; antimicrobial agents; antipsychotic agents; antiviral agents; blood glucose lowering drugs; calcium channel modulators; diuretics; erectile dysfunction agents; gastric acid secretion inhibitors; histamine H2-receptor antagonists; inhibitors of steroid Type II 5o-reductase; lipid regulating agents; selective Hl-receptor antagonists; vasodilators; and vitamins.

[0074] The coating composition is applicable to tablet cores that comprise one or more acidic pharmaceutically active ingredients. Pharmaceutically active ingredients having a pKa value of 1 to 8 are considered acidic pharmaceutically active ingredients. These acidic active pharmaceutical ingredients can cause incompatibilities with coatings containing basic pigments, such as carbonates. The coatings are not subject to such incompatibilities.

[0075] The core may include tableting excipients. Tableting excipients include fillers such as lactose, cellulose powder, calcium diphosphate, microcrystalline cellulose, sugar alcohols, e.g., mannitol, sorbitol and starch, disintegrants such as starch (derivatives), croscarmellose, cross-linked polyvinylpyrrolidone (crospovidone), carboxymethyl cellulose (CMC); lubricants such as stearic acid, magnesium stearate; glidants such as silicon dioxide (Aerosil®); or mixtures thereof.

[0076] Method for preparing the

[0077] The invention further relates to a method for preparing the coating composition as described above. The method comprises the steps of

[0078] (I) dissolving a polymeric film-former as described above in water to obtain an aqueous solution, and

[0079] (II) dispersing a gloss agent being sodium stearyl fumarate as described above to the aqueous solution. Preferably, step (i) involves maintaining the temperature in the range of from 10 to 30 °C, more preferably 15 to 25 °C.

[0080] The process for preparing the coating composition includes dissolving the polymeric film-former in water to obtain an aqueous solution (i), adding the gloss agent to the aqueous solution (ii), optionally followed by adding further constituents of the composition, if any present, e.g. wetting agent, waxy component, glidant etc. as described above.

[0081] The preparation of the coating composition is simplified, as no high shear mixer for particle disaggregation is required. Sodium stearyl fumarate can be dispersed in water at room temperature. Thus, advantageously, no heating of the components of the coating composition is required. This advantageously also allows for applying the inventive coating compositions for coating temperature sensitive tablets cores.

[0082] The coating techniques in which the coating composition can be used are not particularly limited. They include sugar coating, organic solvent based film coating, aqueous based film coating, delayed release coating and granule coating techniques. Preferably, the coating composition is an aqueous film coating composition. The amount of coating applied will depend upon several factors, including the nature and functionality of the coating, the substrate to be coated and the apparatus employed to apply the coating. The coating compositions may also be suitable for high volume batch process and continuous coating operations.

[0083] The present invention is further illustrated by the examples and drawings that follow.

[0084] Fig. 1 depicts tablets top-coated with inventive coating composition 4.

[0085] Fig. 2 depicts tablets coated with comparative coating compositions 5 and 6, and with inventive coating compositions 7 to 10.

[0086] Examples

[0087] Methods

[0088] Dispersion of the components of the coating compositions, e.g. sodium stearyl fumarate, pigments, talc etc., was carried out using a SilentCrusher M device (available from Heidolph).

[0089] Tablet manufacturing was carried out using rotary press XL 100 (available from Korsch) having concave 9 mm punches without embossing. Coating experiments were carried out using a drum coater XL Lab01 device (available from Manesty). The specifications were as follows:

[0090] - drum diameter 406 mm

[0091] - drum speed 27 rpm

[0092] - nozzle diameter 0.8 mm or 1.2mm

[0093] - atomization & pattern air pressure 1 .0 bar

[0094] - inlet air temperature 55 °C or 70 °C, at 280 m3 / h air rate

[0095] - spray rate 15 g / min

[0096] Water vapor sorption determination were carried out using a Vapor Sorption Analyzer - SPS device (available from proUmid). The determination was carried out continuously at 40 °C and 75% r.h. The determined values of water sorption are given as Am based on initial net weight [%].

[0097] Colorimetry measurements for determining color values were carried out using a Datacolor 400V device (available from datacolor). The specifications were as follows:

[0098] - aperture USAV,

[0099] - light D65 10°,

[0100] - n=3

[0101] Disintegration tests were carried out using a ST 50 device (available from Sotax). For each disintegration test, six tablets were investigated at 37 °C in 800 mL of 0.08 mol / L hydrochloric acid.

[0102] Example 1 - Moisture protection

[0103] Moisture protection properties of a comparative coating composition 1 and an inventive coating composition 2 were tested on moisture sensitive herbal extract tablets (commercially available from an external supplier) via water vapor sorption. The moisture sensitive herbal extract tablets had the following properties:

[0104] - 239 mg weight,

[0105] - 107 N crushing force (hardness),

[0106] - 4.9 mm height,

[0107] - 8 mm diameter,

[0108] - water sorption after 100 h at 40 °C and 75% r.h.: 20.5% The following two coating compositions were prepared (see tables 1 and 2):

[0109] Table 1. Comparative coating composition 1 (20% solid matter content):

[0110] 500 g of water were added to Kollicoat® Smartseal (polymeric film-former). While stirring, dibutyl sebacate (plasticizer) was added to the mixture. Iron oxide brown (pigment) and talc were dispersed in the remaining water for 8 min at 15.000 rpm using the SilentCrusher M. The resulting iron oxide brown dispersion was added to the polymeric film-former-plasticizer-mixture. The final coating composition was kept stirring for 1 h.

[0111] Table 2. Inventive coating composition 2 (20% solid matter content):

[0112] Iron oxide brown (pigment) was dispersed in the water for 8 min at 15.000 rpm using the SilentCrusher M. Soluplus® (polymeric film-former, surfactant) was dissolved in the pigment-dispersion. Sodium stearyl fumarate (gloss agent) was added and dispersed for 5 min at 8.000 rpm using the SilentCrusher M.

[0113] Coating composition 1 was applied to 2.0 kg of the moisture sensitive herbal extract tablets using the drum coater XL Lab01 device (nozzle diameter 1.2 mm, inlet air temperature 55 °C) until a weight gain of 15% was achieved. Coating composition 2 was applied to a further batch of 2.0 kg of the moisture sensitive herbal extract tablets using the drum coater XL Lab01 device (nozzle diameter 0.8 mm, inlet air temperature 70 °C) until a weight gain of 15% was achieved. Samples were taken at 5%, 10% and 15% weight gain. After reaching the final weight gain of 15%, a polishing step was carried out in the coater for 15 min at the same coater settings without spraying. Prior to water vapor sorption, the coated tablets were stored for 72 h at 20% r.h. and 23 °C. Water vapor sorption experiments were carried out for three single tablets coated with the comparative coating composition 1 , and for three single tablets coated with the inventive coating composition 2. The results are shown in table 3.

[0114] Table 3.

[0115] * comparative example

[0116] Moisture protection was achieved with the inventive coating composition based on sodium stearyl fumarate. Water sorption depends on the coating quantity applied.

[0117] Example 2

[0118] Coating compositions 3 and 4 were prepared as shown in table 4.

[0119] Table 4. Coating compositions 3 and 4 (20% solid matter content):

[0120] ‘comparative example

[0121] Iron oxide brown (pigment) was dispersed water for 10 min at 15.000 rpm using the SilentCrusher M. Soluplus® (polymeric film-former, surfactant) was dissolved in the pigment-dispersion. Sodium stearyl fumarate (gloss agent) was added and dispersed for 10 min at 12.000 rpm using the SilentCrusher M.

[0122] Coating composition 3 was applied to 2000 g of the moisture sensitive herbal extract tablets of example 1 using the drum coater XL Lab01 device at a nozzle diameter of 0.8 mm and an inlet air temperature of 70 °C until a weight gain of 15% was achieved to obtain sub-coated tablets. Then, the sub-coated tablets were top-coated with coating composition 4 using the drum coater XL Lab01 device at the same conditions until a further weight gain of 5% was achieved. A polishing step was carried out in the coater for 10 min at the same coater settings with water spraying (150 g). The resulting top-coated tablets are depicted in Fig. 1. As can be seen from Fig. 1 , the top-coated tablets showed a high gloss. The top-coated tablets had a smooth hand feel.

[0123] Example 3 - Gloss, disintegration, color

[0124] Impact of sodium stearyl fumarate on gloss, disintegration and color in coating compositions was investigated.

[0125] 2.0 kg of tablets as shown in table 5 were prepared using rotary press XL 100.

[0126] Table 5. Tablets.

[0127] The tablets had the following properties:

[0128] - 325 mg weight,

[0129] - 2.94 N / mm2tensile strength,

[0130] - 107 N crushing force (hardness),

[0131] - 5.05 mm height,

[0132] - 9.08 mm diameter.

[0133] Coating compositions 5 to 10 having varying ratios of crospovidon / sodium stearyl fumarate were prepared as shown in table 6.

[0134] Table 6. Coating compositions 5 to 10 (20% solid matter content):

[0135] 1] polymeric film-former

[0136] [2] sodium stearyl fumarate

[0137] ‘comparative example

[0138] Kolliphor® SLS (surfactant) was dissolved in 1600 g of water. Sodium stearyl fumarate (gloss agent), if present, was dispersed in the Kolliphor® SLS solution for 4 min at 14.000 rpm using the Silent Crusher M. Kollidon® GLI (opacifier), if present, was added to the mixture and stirring was continued for 5 min. Then, Kollicoat® IR (polymeric film-former) and the colorant were added, and stirring was continued for 45 min using a magnetic stirrer.

[0139] The coating compositions were applied to batches of 1800 g of the prepared tablets (as described above) using the drum coater XL Lab01 device at a nozzle diameter of 0.8 mm and an inlet air temperature of 55 °C until a coating level of 16 mg / cm2was reached (2 mg / cm2= 118.6 g applied coating composition, 4 mg / cm2= 237.3 g, 6 mg / cm2= 335.9 g, 8 mg / cm2= 474.5 g, 10 mg / cm2= 593.2 g, 12 mg / cm2= 711.8 g, 14 mg / cm2= 830.4 g, 16 mg / cm2= 949.1 g). Samples were taken at several coating levels. Once the final coating level of 16 mg / cm2was reached, a polishing step was carried out in the coater for 10 min at the same coater settings with water spraying (150 g).

[0140] The resulting coated tablets are shown in Fig. 2. The numbers in Fig. 2 correspond to the numbers of coating compositions (as shown in table 7) with which the tablets were coated. As can be seen from Fig. 2, sodium stearyl fumarate has a significant impact on tablet's gloss after the polishing step. The higher the sodium stearyl fumarate content the higher is the gloss. Tablets with superior gloss were obtained with inventive coating composition 10 comprising 50 wt.-% of sodium stearyl fumarate. The gloss of the coating from coating composition 9 comprising 40 wt.-% sodium stearyl fumarate is slightly weaker compared to coating composition 10. Inventive coating compositions 7 and 8 comprising 20 wt.-% and 30 wt.-% of sodium stearyl fumarate, respectively, result in coatings having a silky matt sheen. Comparative coating compositions 5 and 6 resulted in dull coatings.

[0141] Disintegration tests with the obtained coated tablets were carried out. The results are shown in table 7.

[0142] Table 7. Disintegration test results.

[0001] mean value of six measurements

[0143] ‘comparative example

[0144] As can be seen from the results shown in table 7, sodium stearyl fumarate in the coating has no slowing effect on the disintegration performance of the polished tablets at a coating level of 16 mg / cm2.

[0145] Color values of the obtained coated tablets with different coating levels were determined. The results are shown in table 8.

[0146] Table 8. Color values L, a and b.

[0147] ‘comparative example As can be seen from the results shown in table 8, the color values before polishing were not affected by sodium stearyl fumarate in the coating.

[0148] Example 4 - Opacity

[0149] For investigating opacity properties of the inventive coating compositions, tablets were sub-coated with a dark blue coat (sub-coat). Then, a top-coat was applied from coating compositions according to the invention.

[0150] A batch of the tablets prepared according to table 5 of example 3 was sub-coated using a blue sub-coating composition of 198 g (99 wt.-%) of Kollicoat IR and 2 g (1 wt.-%) of FD&C blue. The sub-coating composition was prepared by dissolving Kollicoat IR and the colorant in 800 g of water. Sub-coating was carried out in the drum coater XL Lab01 device at a nozzle diameter of 0.8 mm and an inlet air temperature of 55 °C until a coating level of 8 mg / cm2was reached.

[0151] Top-coating compositions 11 and 12 were prepared as shown in table 9.

[0152] Kolliphor® SLS (surfactant) was dissolved in 1600 g of water. Sodium stearyl fumarate (gloss agent) was dispersed in the Kolliphor® SLS solution for 10 min at 12.000 rpm using the Silent Crusher M. Then, Kollicoat® IR (polymeric fil-former) was added, and stirring was continued.

[0153] Top-coating was carried out in the drum coater XL Lab01 device using the sub-coated blue tablets at a nozzle diameter of 0.8 mm and an inlet air temperature of 55 °C until a coating level of up to 24 mg / cm2was reached.

[0154] Tablets having top-coatings of the inventive coating-composition 11 with coating levels of 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 mg / cm2were prepared. Coating composition 11 resulted in coatings having a good opacity (especially at coating levels above 14 mg / cm2). Good gloss was obtained at coating levels above 4 mg / cm2. Due to polishing effects at exposed areas of the tablets, abrasion effects occurred, particularly on the edges of the tablets. Tablets having top-coatings of the inventive coating-composition 12 with coating levels of 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 mg / cm2were prepared. Coating composition 12 resulted in coatings having a good opacity (especially at coating levels above 20 mg / cm2). In comparison to coating composition 11 , coating composition 12 resulted in less opaque coatings. Good gloss was obtained at coating levels above 6 mg / cm2. In comparison to coating composition 11 , less abrasion effects occurred. In other words, the tablets coated with coating composition 12 showed good uniformity.

Claims

Claims1. A coating composition comprising a) a polymeric film-former, and b) 20 wt.-% or more, relative to the solids content of the coating composition, of a gloss agent being sodium stearyl fumarate.

2. The coating composition of claim 1, comprising 40 wt.-% or more of the gloss agent.

3. The coating composition of claim 1 or 2, comprising at least one surfactant.

4. The coating composition of any one of the preceding claims, wherein the polymeric film-former is selected from polyvinylpyrrolidone (PVP), polyvinylpyrrolidone-vinyl acetate copolymer (copovidone), methylcellulose (MC), ethyl cellulose (EC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (sodium CMC), polydextrose, starch, modified starch, polyvinyl alcohol (PVA), copolymers based on polyvinyl alcohol, polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate, methacrylate-based polymers, polyethylene glycols, graft polymers based on polyethers, and combinations thereof.

5. The coating composition of claim 4, wherein the polymeric film-former is selected from copolymers based on polyvinyl alcohol, methacrylate-based polymers, copolymers based on polyethylene glycol, and combinations thereof.

6. The coating composition of any one of the preceding claims, additionally comprising at least one of an opacifier, a colorant and a pigment.

7. A coated tablet comprising1) a tablet core, and2) a coating comprising a) a polymeric film-former, and b) 20 wt.-% or more, relative to the solids content of the coating, of a gloss agent being sodium stearyl fumarate.

8. The coated tablet of claim 7, wherein the surface coverage of the coated tablet with the coating is 6 mg / cm2or more, preferably 12 mg / cm2or more, more preferably 14 mg / cm2or more, in particular 24 mg / cm2or more.

9. The coated tablet of claim 7 or 8, wherein the coating additionally comprises at least one surfactant.

10. The coated tablet of any one of claims 7 to 9, wherein the coating additionally comprises at least one of an opacifier, a colorant and a pigment.11 . The coated tablet of any one of claims 7 to 10, wherein the tablet core comprises at least one pharmaceutically active ingredient.

12. A method for preparing the coating composition of any one of claims 1 to 6, the method comprising the steps of(i) dissolving a polymeric film-former in water to obtain an aqueous solution, and(ii) dispersing a gloss agent being sodium stearyl fumarate to the aqueous solution.

13. The method of claim 12, wherein step (i) involves maintaining the temperature in the range of from 10 to 30 °C, preferably 15 to 25 °C.

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