Acrylic enteric coating compositions

Description

(57) Extract The invention provides a non-toxic, edible, enteric film-coatable, dry powder formulation for use in the preparation of an aqueous, enteric suspension suitable for coating pharmaceutical tablets, the formulation comprising a) an acrylic resin containing at least one vinyl or vinylidene moiety having a carboxylic acid group capable of forming salts, b) an alkalizing agent capable of reacting with the acrylic resin in such a way that after the reaction, 0.1 to 10 mol% of the acid groups in the vinyl or vinylidene moiety are in the form of a salt; and c) a tack-reducing agent. 42230 Beiben soluble ak.nl coating The invention relates to the field of coating pharmaceutical tablets with an aqueous, enteric (enteric) film coating and relates to coating compositions for preventing the release of the active ingredients of the coated tablet in gastric juice and for releasing the active ingredients of the tablet in the intestines. More specifically, the invention provides a fully formulated, non-toxic, edible, enteric film coating dry powder composition based on acrylic resin for the preparation of an aqueous, enteric coating suspension, which can be used in the coating of pharmaceuticals with an enteric coating and which is insoluble in the gastric juice of the stomach. Several aqueous enteric film coating systems are known: Such systems include the AQUATERIC system, which is based on cellulose acetate phthalate, SURETERIC based on polyvinyl acetate phthalate (PVAP), and the EUDRAGIT L system, which is based on copolymers of acrylic acid esters and methacrylic acid esters. The AQUATERIC and EUDRAGIT L systems require at least three processing steps to form the enteric coating suspension. In the case of the AQUATERIC system, the AQUATERIC powder is dispersed in water, and then Tween 80, a plasticizer, and optionally pigments, are added in batches to form the AQUATERIC suspension. The EUDRAGIT L system is available in powder form (L10055) or as an aqueous dispersion (L30-D). The ..EUDRAGIT L Teohnical Application Pamphlet (Info LÖ-13 / e}” describes a multi-step process for the preparation of an aqueous enteric dispersion, which includes the following steps: 1) EUDRAGIT L100-55 powder is added to water; 2) a pre-calculated amount of aqueous sodium hydroxide solution is added to it, as appropriate; 3} the dispersion is mixed using a simple mixer at a medium and controllable speed for 30 minutes; 4} the suspension is filtered off; 5} then an aqueous solution of a plasticizer (recommended amount of 10% by weight based on EUDRAGIT L100-55 powder), a "separating agent" and a thickener are added to the filtered suspension; 6) further mixing; 7) final filtration.Special precautions are warned about in the brochure, which include the warning that coagulation of the EUDRAGIT L aqueous dispersion may occur due to the presence of electrolytes, foaming, exposure to heat or frost, the presence of finely divided pigments and exposure to strong shear forces when using high-speed mixers and grinders. Special caution is given to adhere to the specified formulation ratios, as deviations can result in the formation of a coagulum which, according to the brochure, is “unable” to be dispersed, rendering the entire aqueous dispersion “unusable”. EUDRAGI i L3Ö-D suspension is a 30% by weight pre-neutralized aqueous dispersion of ethyl acrylate / melacrylic acid copolymer. Published by A. Rohm Pharroa GmbH IT L ] lloafloh Parophlef Union LD-11 / e)” provides a procedure for the preparation of a complete aqueous dispersion system based on EUDRAGIT L3Ö-D suspension, which includes the following steps: 1) addition of softening agent; 2) addition of “separating agent; 3) addition of dispersant; 4) addition of pigments, if applicable; 8) mixing; and 8) final filtration. The same special precautions as those described for EUDRAGIT L100-55 powder are also listed in the brochure for EUDRAGIT L3Ö-D suspension. The SURETERIG formulation disclosed in Colomon's U.S. Patent No. 5,733,575 advances the prior art by describing a complete formulation of an enteric film coating preform which, together with an antifoam, can be readily dispensed in water in two steps. The SURETERIG system requires the addition of a viscosity modifier to prevent the settling of suspended solids in the resulting aqueous dispersion during coating. Lebmann et al. in U.S. Patent No. 4,528,172 describe a two-component mixture of EUDRAGIT L. copolymer and a suitable alkalizing agent or "souring agent". However, no enteric film coating systems based on the εW-acrylic acid copolymer EUDRAGIT L system are currently known that are analogous to the SURETERIG system.Furthermore, considering the precautions cited in the Rohm & Rhamna literature and the chemical differences between PVAP and methacrylic / ethylene acrylate copolymers, it would be surprising and unexpected if the two-component system described by Lehmann et al. could be formed into a fully formulated, solid preparation that could be easily dispersed in water to provide an enteric coating. The object of the invention is to provide a fully formulated enteric film coating composition based on EUDRAGIT L copolymers, which is readily dispersible in water and can be used on pharmaceutical tablets, and which is defined in the claims, It is a further object of the invention to provide a fully formulated enteric film coating composition based on EUDRAGIT L copolymers which does not aggregate during its manufacture. A further object of the invention is to provide a fully formulated enteric film coating composition based on EUDRAGIT L copolymers which does not form tomates during storage at high temperatures and high humidity. The invention further provides a fully formulated enteric film coating composition based on EUDRAGIT L copolymers which is readily dispersible in water to form a coating dispersion which, when applied to pharmaceutical tablets, provides a coating which is non-tacky. It is a further object of the invention to provide a fully formulated enteric film coating composition comprising a lacquer pigment and a neutralizing agent, wherein the lacquer pigment remains stable upon dispersion in water. Another object of the invention is to provide a fully formulated enteric film coating composition based on EUDRAGIT copolymers which is easy to It is a coating that, when applied to a surface, forms a film coating with exceptional film strength. This exceptional film strength is reflected in the excellent performance obtained in the "disintegration under load" test. It is a further object of the invention to provide a fully formulated enteric film coating composition based on EUDRAGIT L copolymers which disperses in water without the formation of coagulants. It is a further object of the invention to reduce the number of steps in the preparation of aqueous film coating dispersions based on EUDRAGIT L copolymers from six (0) or more to two (2), and thus, as a beneficial result, the total preparation time for the preparation of aqueous film coating dispersions is reduced from 90 minutes to 20 minutes. According to the invention, a non-toxic, edible, enteric-coated dry powder composition for the preparation of an aqueous, enteric-soluble suspension for coating pharmaceutical tablets comprises an acrylic resin (e.g. EUDRAGIT 1 copolymer(s)), an alkalizing agent and a tack-reducing (inhibiting) agent. Optionally, but preferably, the dry powder composition according to the invention may further comprise one or more additives from the following: a plasticizer; a pigment; a flow-promoting agent; a surfactant; an agglomerate-preventing (reducing) agent; a secondary film-forming agent; and a secondary tack-reducing agent. In a particularly preferred embodiment of the invention, the novel; The dry powder formulation contains acrylic resins, an alkalizing agent, a tackifier, a plasticizer, a pigment, a flow aid, a surfactant, an anti-agglomeration agent, a secondary film former, and a secondary tackifier. The novel dry powder formulation comprises a process for preparing a resin with an alkalizing agent, a tackifier and optionally one or more of the following: a plasticizer; a pigment; a flow aid; a surfactant; an anti-agglomeration agent; a secondary film former and a secondary tackifier. The resulting enteric-soluble, film-coated, dry powder formulation and a separately added antifoam are readily dispersed in water, preferably deionized water, using a high shear mixer and the dispersion is ready for use within 15-30 minutes. A high shear mixer is preferred over a slower mixer to eliminate the formation of coagulants. According to the invention, the coating process for substrates, such as pharmaceutical tablets, comprises successively mixing an antifoaming agent and the dry composition of the invention in water to obtain a coating suspension, then applying the coating suspension to the substrate to be coated to form a film coating on the substrates, and drying the film coating. The soluble polymer is an acrylic resin containing at least one (legaoiyan vW- or vinylidene moiety) which has vosöooates. The acrylic resin may contain at least one alkyl acrylate or alkyl mefacrylaf moiety, or vinyl or vinyl or vinylic of these. Furthermore, the acrylic resin may contain le< vinylidene moiety having a carboxylic acid group capable of forming a salt. at least one alkyl acrylate or alkyl methacrylate moiety and at least one vinyl or vinylidene moiety copolymerizable with a) alkyl acrylate or alkyl methacrylate moiety and b) vinyl or vinylidene moiety having a carboxylic acid group capable of forming a salt, or may consist of such. Furthermore, the acrylic resin may comprise at least one vinyl or vinylidene moiety having a carboxylic acid group capable of forming a salt, or may consist of such. Preferably, the enteric polymer is an acrylic resin comprising (1) 20-85% by weight of at least one alkyl acrylate or alkyl methacrylate moiety; (2) 80-15 (i) at least one vinyl or vinylidene moiety; and (3) 0-30% by weight of at least one other vinyl or vinylidene moiety copolymerizable with (1) and (2). In a particularly preferred embodiment of the invention, the acrylic acrylate (1) is ethyl acrylate and the vinyl moiety (2) is methacrylic acid. EUDRAGIT 1100-55 powder is an example of a copolymer system meeting this definition. The acrylic resin preferably comprises from about 20 to about 80% by weight of the dry coating composition of the invention. The alkalizing agent may be, for example, sodium or potassium hydrogen carbonate, carbonate, phosphate or hydroxide, magnesium carbonate, magnesium hydroxide, ammonium carbonate, ammonium hydrogen carbonate, magnesium oxide, calcium hydroxide or any of these. The amount of alkalizing agent used is directly proportional to the amount of carboxylic acid-carrying vinyl or vinylidene moiety in the acrylic resin. about the aforementioned hanger .. The .. after reaction with mercury resin, 0.1-10 mol% of acid groups should be present in the salt form, The tackifier may be talc, aluminum hydrate, glycine monostearate, kaolin, or a combination thereof, and is used in principle to reduce the sticking of tablets to tablets which may occur during the film coating of pharmaceutical tablets and the like when aqueous dispersions based on the compositions of the invention are used. Preferably, the dry coating composition of the invention contains from about δ to about 40% by weight of tackifier. The plasticizer may be diethyl phthalate, triethyl citrate, glycerol triacetate, acetyl triethyl citrate, dibutyl sebacate, diethyl phthalate, polyethylene glycol having a molecular weight of 200-8000, glycerin, castor oil, copolymers of propylene oxide and ethylene oxide, or a combination thereof. If the dry powder composition of the invention does not contain a plasticizer, the plasticizer is separately mixed into the coating suspension of the invention. Preferably, the plasticizer comprises 0 to about 20% by weight of the coating composition of the invention, more preferably about 2 to about 20% by weight of the dry coating composition of the invention. The pigment may be, for example, an FD&C or D&C lake, titanium dioxide, magnesium carbonate, phthalate, fumed silica, iron oxides, carbon black, riboflavin, carmine 40, curcumin, annatto, insoluble dyes, a pearlescent pigment based on mica and / or titanium dioxide, or any combination thereof. Other suitable pigments are listed by Jeffries in US Patent No. 3,149,040; Butler et al. in US Patent No. 3,297,535; and Colomon in US Patent No. 3,991,984. The pigment may also comprise lacquer mixtures containing a plasticizer and OPADRY pigmented coating compositions, some of which are disclosed in U.S. Patent No. 4,543,370 to Colomon. Preferably, the pigment comprises from 0 to about 50 wt% of the novel dry coating composition. The flow aid may be, for example, silicon dioxide, such as colloidal silicon dioxide, which is available from Gebet Inc. under the trade name Cab-O-Silicone. The flow aid provides fluidity to the composition during dry mixing and subsequent transfer from the bag to the container. Preferably, the dry coating composition has a viscosity of about 100 to about 1000 psi. V is exposed to the flow-enhancing material, The surfactant may be, for example, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, polysorbate 80, Tween 80, or a mixture of any combination thereof. Preferably, the surfactant comprises from 0 to about 5% by weight of the novel dry composition. The anti-agglomeration agent may be, for example, kaolin. The amount of the anti-agglomeration agent in the novel dry coating composition is δ - about 40% by weight, based on the coating composition. We have surprisingly found that a relatively small amount of kaolin prevents agglomeration during the preparation of the powder composition and during storage of the final composition at elevated temperature and humidity. Preferably, the kaolin is used in an amount greater than 0% by weight and less than about 40% by weight, based on the composition. We have unexpectedly found that a given amount of kaolin; provides a much greater degree of anti-agglomeration effect than the same amount of talc or silica, which are also known as anti-agglomeration agents. Preferably, the kaolin serves both as an anti-agglomeration agent and as a tackifier. A secondary film maker can be e.g. xanthan gum, sodium aginate, propylene glycol alginate, hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose (HEC), sodium carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVF), Konjac flour, carrageenan, other film-forming polymer or a combination thereof. Preferably, the amount of secondary film-forming agent in the coating composition is 0 to about 5% by weight based on the dry coating composition of the invention. The use of the secondary film-forming agent improves the film-forming property of the composition of the invention in a very low amount, as shown by the coating performance obtained in the Colomon “on-demand, enteric dissolution test”. In a preferred embodiment of the invention, the new composition comprises a xanthan gum in an amount of 0.0% by weight based on the dry coating composition of the invention. Adding gum is better during bowel movements compared to preparations without xanthan gum. The secondary tackifier may be sodium sulfate, calcium sulfate, calcium chloride, other organic or inorganic water-complexing agents, or a combination thereof. Preferably, the amount of secondary tackifier is from 0 to about 5% by weight of the dry coating composition of the invention. Surprisingly, the amount of secondary tackifier is very low (m 5. as 0-5 fc results in a dramatic reduction in tablet stickiness after the tablets are coated with the aqueous dispersion film of the invention for the most stick-prone formulations. In a preferred embodiment of the invention, the addition of only 0.18% by weight of calcium sulfate based on the formulation results in the formation of stick-free tablets when coated with the novel aqueous dispersions. Surprisingly, a given level of calcium sulfate or similar water-complexing compound is much more effective in reducing stickiness than the same amount of other talc and glycerol monosphaera.It can be stated that the secondary tackifier acts as a water complexing agent and binds free water on the tablet surface, preventing water from interacting with the blended polymer, thus effectively increasing the glass transition temperature (Ts) of the polymer and its resistance to further softening and the accompanying adhesion to similar tablets. It is particularly advantageous to add as many beneficial additives as possible to the composition according to the invention. Therefore, a composition according to a particularly preferred embodiment of the invention comprises: (1) an acrylic resin, preferably in an amount of about 20 to about 80% by weight of the composition; (2) a solvent, present in the composition in an amount such that about 0.1 to 10 mol% of the carboxylic acid groups of the acrylic resin are neutralized; (3) a tackifier, preferably in an amount of about 5 to about 40% by weight of the composition; (4) a plasticizer, preferably in an amount of about 2 to about 20% by weight of the composition; (5) a pigment, preferably in an amount of more than 0% by weight of the composition, up to about 0% by weight; Sj flow aid, preferably in an amount greater than 0% by weight of the composition and up to about 3% by weight; 7) surfactant, preferably in an amount greater than 0% by weight of the composition -9) a high concentration, up to about 5% by weight; 8) an agglomeration inhibitor, preferably from about 0% by weight of the composition to about 48% by weight; 9) a secondary film former, preferably from about 0% by weight of the composition to about 5% by weight; and 10) a secondary tackifier, preferably from about 0% by weight of the composition to about 5% by weight. It has been unexpectedly found that when the said fully formulated pigment varnish composition is dispersed in water, the pigment varnish is completely stable. No color bleeding is observed. This is particularly surprising in view of current industry practice which dictates that "colorants should only be added to the dispersion after the neutralization step (reaction of the acrylic polymer with the neutralizing agent) in order to avoid color bleeding." The compositions of the invention are preferably prepared by conventional dry mixing using a "V-shaped" mixer, food processor or similar equipment. The compositions of the invention prepared by such conventional mixing techniques are dispersed in an aqueous solution using a high shear mixer prior to film coating of substrates, such as pharmaceutical tablets and the like. The use of a high shear mixer allows for the formation of a homogeneous aqueous dispersion without the formation of problematic coagulants. The following examples are provided. the find Example 1 Aspirin seeds (full batch 2.5 kg; 325 mg) were coated successively with a bottom coating dispersion made of a white Opadry® II coating composition (#574-39 composition} and an enteric coating suspension made of the composition according to the invention. First, the Opadry II bottom coating dispersion was prepared by adding dry Opadry II composition (50 g) to deionized water (250 g), then the mixture was mixed for 30 minutes using a propeller mixer. Thus, a homogeneous dispersion was obtained. The enteric-coated dry powder preparation of the invention according to Example 1 LtOÖ-55 powder (120.3 g; 43.13 wt.%), sodium hydrogen carbonate (3.6 g; 1.44 wt.%), talc (57.3 g; 22.93 wt.%), Pigment lacquer (9.5 g; 3.8 wt.%), titanium dioxide (14.3 g; 5.7 wt.%), colloidal silicon dioxide (3.3 g; 1.25 wt.%), sodium lauryl sulfate (1.25 g; 0.5 wt.%), kaolin (12.5 g; 5 wt.%) and xanthan gum (0.625 g; 0.25 wt.%) were prepared by thoroughly mixing for 10 minutes in a food processor. To this solid mixture was added sodium citrate (27.5 g; 11 wt.%). After another 2 minutes of mixing, a homogeneous, free-flowing powder was obtained, free of visible agglomerates. The enteric suspension of the invention was then prepared by pre-dispersing Antifoam Eö-10 antifoam (1 g) into deionized water (1.25 kg) using a Silverson high-torque mixer (Model L-4RT-A) equipped with a general purpose dispersion head (i.e., GPDH ring) operated at 1500-2000 rpm for 2 minutes with the stator positioned in the center of the vessel. The mixer speed was increased to 10,000 rpm and the enteric dry powder formulation of the invention (250 g) was gradually added to the vortex at a rate sufficiently slow to avoid clumping (approximately one minute). After the addition was complete, the stator was moved away from the center of the vessel to minimize air pockets, and the suspension was further agitated at 10,000 rpm for an additional ten (10) minutes. / min to obtain a homogeneous suspension containing no visible agglomerates, where neither pigment degradation nor color bleeding is observed. A 38.1 cm diameter O'Hara LabGoat 1 dragee pan equipped with a pump head, Cole-Parmer K / lasterftex pump, platinum-cured silicone tubing (15 gauge), and a Spraying Systems spray gun (0.3175 cm VAU SS; fluid nozzle-W60100-SS: air cap-VA1282125SÖ-SS) was loaded with aspirin cores (total batch 2.5 kg; 325 mg aspirin per tablet). The tablets were sequentially coated with the Opadry II undercoat dispersion and the enteric suspension of the invention under the following processing conditions. Coating process parameters (38.1 cm O'Hara LabGoat1) Fluid flow rate (g / min) Atomizing pressure (kPa) The speed of the kettle (f / min) 5 coating In H soluble 30 20 137.5 137.6 206.4 206.4 43 30 16 17 coating Neither stickiness nor sticking between tablets was observed during the coating process. The finished coated tablets are classified according to the United States Pharmacopeia (USP) <711> The dissolution test was performed according to the "delayed release" aspirin monograph. As specified in the test, six tablets coated as described in Example 1 were placed in 0.1 N HCl for 2 hours at 37°C. During the acidic phase of the test, the release of the active ingredient was 0.1%, compared to the upper limit of 10%. The six tablets were then placed in phosphate buffer (pH ∼6.8) and after 90 minutes the amount of aspirin released was 35% greater than 80%, compared to the requirement that the release after 90 minutes should not be less than 80%. The finished coated tablets were also evaluated using a modified version of the USP <70> disintegration test. 50 tablets, the The tablets prepared as described in Example 1 were subjected to 100 revolutions in an attrition tester. The 50 used tablets were then placed in a basket unit and soaked in a gastric juice-like liquid (0.1 N HCl) for one hour. The basket was moved upwards at a speed of 100 rpm similar to that of the weed killer. 50 unused tablets were also placed in one and soaked in a gastric juice-like liquid for one hour. After removal from the gastric juice-like liquid, the tablets were determined to be intact. In all cases (used and unused tablets), the tablets did not show signs of swelling or breakage. The finished coated tablets were also qualitatively examined. The resulting orange-colored coating was smooth and uniform and showed no evidence of adhesion, weathering or uneven color. >2 Example 2-5 Examples 2-5 relate to compositions according to the invention and suspensions according to the invention prepared in a manner analogous to the process described in Example 1, with minor modifications to the composition as detailed in the following table. In each of Examples 2-5, the compositions according to the invention were agglomerate-containing, free-flowing (free-flowing) granules which, when suspended in water, resulted in suspensions in which there were no visible coagulants and no pigment degradation or color bleeding was observed. In each of Examples 2-5, no woodiness was observed during the coating step. All tablets appeared smooth and uniform in both texture and color. Differences in dissolution test behavior were noted depending on the xanthan gum content.The presence of xanthan gum in the formulations resulted in improved performance in the stressed dissolution test, strongly suggesting that film strength and impermeability are significantly increased when only small amounts of xanthan gum are added to the formulation. Comparative data table - Example 2-5 Weight% in 250 g preparation Components Example 2 Example 3 Example 4 Example 5 Eudragit® L100-55 55.0 55.0 55.0 55.0 Sodium hydrogen carbonate 1.85 1.65 1.65 1.85 Telkem 20.1 20.8 24.8 18.0 Kaolin 5.0 5.0 5.0 5.0 Titanium dioxide 3.0 3.0 3.0 8.4 Yeilow#6 lake pigment 2.0 2.0 2.0 5.8 Sodium lauryl sulfate 0.5 0.5 0.5 0.5 Colloidal silicon dioxide 1.25 n 1.25 125 na 1.25 Kantan gum í í ;U 0.5 ' hv 0.0 Ο-,·Ο· 0.5 0.0 100% 100 % 100% 100% Standard disintegration test Disintegration test with demand bt 100 Example 6-9 Examples 6-9 relate to compositions of the invention and suspensions of the invention prepared in a manner analogous to the process of Example 1, with minor modifications as set forth in the table below. In Examples 6-9, the compositions of the invention were free-flowing powders free of agglomerates which, when suspended in water, gave suspensions in which there were no visible coagulants and no pigment degradation or color bleeding was observed. In Examples 6-9, the seed bed temperature during the tablet coating step was 32-36°C, in contrast to Example 1, where the seed bed temperature was maintained at 30°C. In general, the tendency to increase with increasing seed bed temperature. In Examples 6-9, the seed bed temperature was 32-36°C. sg and the tablets were sticking together. In the tablet coating step, no stickiness was observed in Examples 7-9 during the tablet coating step. The tendency to stickiness at elevated temperatures was compensated for by the addition of very small amounts of a secondary anti-adhesion agent (sodium sulfate, calcium sulfate dihydrate or calcium chloride). At the end of the coating process, all tablets appeared smooth and uniform in both texture and color. comparative data table - example 6-9 Weight% in 250 g preparation Components Example 6 Example 7 Example 8 Example 9 Eadragít® L10G-55 49.0 49.0 49.0 Calcium hydrogen carbonate 1.45 1.47 1.4 / 1.4 / Talc 25.46 25.3 25.3 25.3 Kaolin 5.0 5.0 5.0 5.0 ι-Oiloxide Lacquer Sodium lauryl sulfate Colloidal silicon dioxide Triethyl oleate Sodium sulfate Calcium sulfate dihydrate Calcium ket 5.82 3.88 3.5 1.30 7.8 0.0 3.0 8 0 100 50 5.1 3.1 5 1 28 7.6 0.15 0.0 0.0 100% 5.82 3.88 0.5 1.28 7.6 0.0 0.15 0.0 100% 5.82 0.5 1.28 7.8 0.0 0.0 0.15 100% during Standard dissolution test 100 100 100 -11. Examples 10 and 11 relate to compositions according to the invention and suspensions according to the invention prepared in an analogous manner to the process described in Example 1, with the difference that iron oxide-based dyes were used. Examples 18 and In Example 11, the compositions of the invention were free-flowing powders without agglomerates which, when suspended in water, resulted in suspensions in which there were no visible coagulants and no pigment degradation or color bleeding was observed. In Examples 10 and 11, no stickiness was observed during the tableting step. All tablets appeared smooth and uniform in both texture and appearance. Comparative data table - examples 10 and fi Eudragit® L100-55 Sodium Hydroxide Taikuro Kaolin % in 250 g preparation Example 10 Example 11 50.0 50.0 1.50 1.50 28.25 28.25 5.0 5.0 Titanium dioxide Red iron-exld Yellow iron oxide hlátri o m-ía u ril-su Ifát Colloidal silicon dioxide Tnetii citrate Tablet color Standard disintegration test (appropriate %- 5.1 5.1 3.4 0.0 0.5 0.0 3.4 0.5 1.25 7.0 1.25 7.0 100 % 100 % RED YELLOW 98 100 Example 12-15 Examples 12-15 relate to compositions according to the invention and suspensions according to the invention prepared analogously to the method described in Example 1 with the modifications of the composition detailed in the table below. When the composition contained kaolin, there was no evidence of agglomeration or agglomerate formation in the powder. In contrast, compositions containing talc but not kaolin showed significant agglomeration and agglomerate formation in the powder. The compositions according to Examples 12-15 were tested for color bleeding and the test results showed no color bleeding in the aqueous suspensions prepared from the compositions according to the invention, neither at "time zero" nor after storage for 1 month at 40°C and 75% relative humidity. All tablets appeared smooth and uniform in both texture and color. Comparison Data Table™ 12-15, Example Weight % in 250 g preparation Components Example 12 Example 13 Example 14 Eudragé® L100-55 55.0 55.0 49.0 49.0 Sodium hydrogen carbonate 1.76 1.76 1.57 1.57 Talc 30.0 0.0 27.0 0.0 Tin dioxide YeilowfO ink pigment NafnumdauriEsulfate Glycerin monostearate Tween 80 Covalent silica Trfetit-dtrat Agglomerate Formation - during the preparation of the powder - after 1 month of powder storage: 40cC / 7§ % relative humidity Tablet color Standard disintegration test (corresponding %~bao) 0.0 0.0 30.0 0.0 0.0 5.82 .27.0 0.0 0.0 3.88 3.88 0.5 0.8 0.5 0.5 1.6 1.8 1.5 1.5 2.2 2 zy <yzí 2,0 0,34 8,0 u.34 u} o ü, 3 100 % igen nem fehér narancs 98 94Example 16-18 Example 18-18 relates to compositions of the invention and suspensions of the invention prepared in an analogous manner to the process described in Example 1 with some modifications to the composition as detailed in the table below. When the composition contained kaolin, there was no evidence of agglomeration or agglomeration in the powder. In contrast, compositions containing talc but not kaolin showed significant agglomeration and agglomeration in the powder. The test results showed no color bleeding in aqueous suspensions prepared from the compositions of the invention, neither at "time zero" nor after storage for 1 month at 40°C and 75% relative humidity. All tablets appeared smooth and uniform in both texture and color. Example 18In Example 18, the omission of glycerol monostearate, sodium lauryl sulfate, and Tween 80 from the formulation resulted in coated tablets that were much less shiny or glossy than the tablets of Examples 18 and 17. • 17 Comparison data table--- 16-18, example Components Eudragli® L100-55 Sodium bicarbonate (anhydrous) Talc Kaolin Titanium dioxide Yeilow#6 lacquer pigment N át rio m-la u rü-szuifáí Glycerin monostearate TweenSSQ Colloidal silicium oxide Tnettórát during the preparation of the lerate formation - after 1 month of storage of the powder 40X / 75% relative humidity Tablet size / Appearance Standard disintegration test (filling- Weight0 / Example 18 49.0 27.0 0 0 in 250 g formulation Example 17 49.0 1.65 0.9 27 0 Example 18 49.0 0.0 31 S 5.82 5.82 5.82 3.88 3.88 3.88 0.5 0.5 0.0 A Π 1.0 1.0 UjU 2.0 2.0 0.0 0, 7.75 0.9 7.75 9.0 7.75 100 % 100% 100% YES NO NO YES NO N / A Orange / Orange / Orange / glossy glossy matt 94 98 92 Example 19-26 Examples 19-26 relate to compositions of the invention and suspensions of the invention prepared in an analogous manner to the Leid process in Example 1, except that significant modifications were made to the formulation and the size reduction was made to the powder formulation (100 g), the suspension formulation (500 g) and the coating process (30.45 cm diameter pan; 1 kg aspirin tablet core batch). 1st Judge: - 00 fever - 19-22, example Weight % in 100 g of preparation :VC35! SUi! !'··: Talc Kaolin aun old silpheiumTneil citrate cmm-sulfai-c gum Example 19 Example 20 Example 21 Example 22 60.0 80.0 60.0 60 0 1.8 1.8 1.8 1.8 38.2 31.0 28.5 36.9 0.0 0.0 AAAA 0.0 0.0 & ÖA AAP,v UJJ 0.0 0.0 0.0 0.0 0.0 0.0 0.0 P,ÖZ UJJ 3.88 0.0 0.0 0.0 0.0 0.0 1.3 0.0 7.2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 100% 100% 100% 100% In the appropriate % Standard disintegration! examination Disintegration with demand intake examination is not realistic. 100 White / matt Orange / bird White / matt Comparative data table - examples 23-28 Weight % in 100 g of preparation Eudragit® L. 100-55 Talc Kaolin Titanium dioxide 80.0 1.8 37.7 fi A 24, example 21 60.0 1.8 33.2 £? A 3pél 80.0 1.8 37.7 AA UJJ 0.0 Ö,U 0.0 U,P 0.0 Example 26 60.0 1.8 38.05 0.0 0.0 Yesiow#6 eye pigment Hydrochloric acid sulfate Your poets are syllabic. TnetH-cstrat Calcium sulfate dihydrate Kantan rubber In the appropriate % Standard disintegration! examination Disintegration with demand; examination Tablet szs n / Appearance 0.0 0 / 5 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 Ö 0.0 0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 ,0 0.15 ,5 0.0 100% 100% 1öí ) % 100 % 98 96 94 100 0 o ; ? 0 White / White / Top w / Bottom matt matt m aft matt A non-toxic, edible, enteric film-forming dry powder preparation for use in the preparation of an aqueous, enteric-coated suspension suitable for coating pharmaceutical tablets, the preparation being a tablet or tablet containing a b) a solvent capable of reacting with the acrylic resin in such a way that after the reaction 0.1-10 mol% of the acid groups in the vinyl or vinylidene moiety are in the form of a salt; and

Claims

2. A dry powder composition suitable for forming a non-toxic, edible, enteric film coating according to claim 1, which also comprises a plasticizer, pigment, flow aid, surfactant, anti-agglomerate, secondary film former, secondary tackifier or a combination thereof. A dry powder composition suitable for forming a non-toxic, edible, enteric film coating according to claim 1, wherein the acrylic resin comprises I) 20-85 wt% of at least one alkyl acrylate or alkylene; 80-15 wt% of at least one vinyl or moiety having a carboxylic acid capable of forming a resin; and at least one other vinyl or vinylene moiety, i) and l) respectively.

4. The composition of claim 3.1 which comprises a composition suitable for forming an enteric film coating according to claim 1. •21 5. A dry powder formulation suitable for forming an enteric film coating according to claim 3, which also contains a pigment.

6. A dry powder preparation suitable for forming an enteric film coating according to claim 3, which also contains a flow-enhancing agent.

7. A dry powder composition suitable for forming an enteric film coating according to Claim 3, which also contains a surfactant.

8. A dry powder preparation suitable for forming an enteric film coating according to claim 8, which also contains an anti-agglomerate agent.

9. A dry powder preparation suitable for forming an enteric film coating according to claim 3, which also contains a secondary film-forming agent.

10. A dry powder formulation suitable for forming an enteric film coating according to Claim 3, further comprising a secondary tackifier.

11. Another method for forming a dry enteric film coating, in which the alkyl acrylate is ethyl acrylate and the salt formation is vicinal acid.

12. The enteric film coating according to claim 3 is suitable for forming sodium or potassium magnesium carbonate, magnesium hydroxide, ammonium carbonate, ammonium hydrogen carbonate, magnesium oxide, potassium hydroxide or any of these; the material is falcum, suitable for forming, dry powder preparation, such as aluminum hydrate. glycine monostearate, kaolin cut) Λ. '>2 14. A dry powder preparation suitable for forming an enteric film coating according to claim 4, wherein the blowing agent is triethyl citrate, glycerol triethyl acetyl triethyl citrate, diethyl sebacate, diethyl phthalate, polyethylene glycol with a molecular weight of 200-8000, glycerin, castor oil, a copolymer of propylene oxide and ethylene oxide, or a combination thereof.

15. A dry powder formulation suitable for forming an enteric film coating according to Claim 5, wherein the pigment is FD&C or CMC lake, titanium dioxide, magnesium carbonate, talc, pyrogenic silica, iron oxide(s), ala· 17. A dry powder preparation suitable for forming an enteric film coating according to claim 7, wherein the surfactant is sodium lauryl sulfate, dioctyl sodium sulfosuccinate, polysomat 80, Tween 80 or any other of these, dry, enteric film coating inhibiting agents; 19. A dry powder preparation suitable for forming an enteric film coating according to claim 9, wherein the secondary film-forming agent is xanthan gum, sodium alginate, propylene glycol alginate, hydroxyethyl cellulose (HEC), sodium carboxymethyl cellulose (sodium CMC), polyvinylpyrrolidone (PVP), Konjac flour, carrageenan, other film-forming polymer or any combination thereof. A dry powder preparation suitable for forming an enteric film coating according to claim 10, wherein the secondary tack-reducing agent is sodium sulfate, calcium sulfate, calcium chloride, other inorganic or organic water-complexing agent(s) or any combination thereof.

21. A dry powder composition suitable for forming a soluble film coating according to claim 11, which also contains a plasticizer, a pigment, a flow aid, a surfactant, an agglomerate inhibitor, a secondary film former and a secondary tackifier, the amount of the acrylic resin is 20-80% by weight of the composition, the alkalizing agent is sodium or potassium bicarbonate, carbonate, phosphate or hydroxide, magnesium carbonate magnesium hydroxide, ammonium carbonate ammonium bicarbonate, magnesium oxide, calcium hydroxide or a combination thereof, the tackifier is falcon, aluminum hydrate, glycerol monostearate, kaolin or a combination thereof, the amount of the tackifier is 5-40% by weight of the composition, the plasticizer triethyl ether glycine triacetate, acetyl methyl citrate, dihydrogen sebacate, diethyl phthalate molecular weight 200-8000 polyethylene glycol, glycerin, castor oil,a copolymer of propylene oxide and ethylene oxide, or a combination thereof, the amount of the plasticizer is 2 to 20% of the composition, the pigment is FD&C or D&C lake, mica is a kind of carbonate, spirit, pyrogenic silica, iron oxide), in, carmine 40, curcumin, annatto, or a pearlescent based on titanium dioxide, the following) or these ge the main substance is silicon dioxide, the de %-anate is not more than 3% by weight, the surfactant is sodium taurine sulfate, disodium selphysulphate, polysorbate 80, Tween 80 or a combination thereof, the amount of the surfactant is more than 5% of the composition, but not more than 5 % of the main ingredient, the agglomerate-preventing agent is kaolin, the amount of agglomerate is % of the main ingredient, the secondary film-forming agent is xanthan gum, sodium alginate propylene glycol alginate (PGA), hydroxypropyl methylcellulose (HPMC), hydroxycellulose »24 I,sodium carboxymethyl oleulose (sodium polyvinylpyrrolidone (PVP), ac Ost the secondary film-forming polymer up to 5% by weight, the sulfate, calcium sulfate, potassium chloride n-forming polymer or any of these amounts to 0% of the composition, the sodium inorganic or organic water-complexing agent, or any combination thereof, the amount of the secondary tack-reducing agent up to 5% by weight. % I. A non-toxic, edible, enteric film coating according to claim 1 suitable for use in the preparation of an aqueous, enteric suspension; for use in the coating of pharmaceutical tablets, wherein the acrylic resin contains I) 15-80% by weight of at least one vinyl or vinylidene moiety having a carboxylic acid capable of forming salts) 20-85% by weight at least one composition according to i)-veli vinyl or vinylidene, which is a flow aid, a surfactant,agglomerate inhibitor, a secondary film former, a secondary tackifier or a combination thereof. a non-toxic, edible, enteric film-coating agent for cosmetic products and foodstuffs, suitable for aqueous coating dispersions, including a dry powder preparation, b) a dry alkalizing agent and tackifier according to step a; and c) preparing an aqueous coating suspension by high shearing of the slurry in a similar apparatus in water \ 24, ίε, άραραρα ρειοάαιθη και δεν σγλότερο, surfactant, agglomerate material, secondary tackifier or a combination thereof, and mixing the tackifier with the dry powder suitable for forming a non-toxic dry powder suitable for forming a soluble film coating according to claim 1, which comprises:and applying the aqueous SZUS2 solution of step a) to the substrate; and y. The 26. anti-caking agent, secondary tack reducing agent or one of these, the alkaline: method, characterized in that the softener, secondary tack reducing agent or one of these is combined with the material in the non-price suitable, dry preparation- 28. A dry powder preparation suitable for forming a non-toxic, edible, enteric film coating according to claim 22, wherein the tack reducing agent is selected from the group consisting of talc, aluminum hydrate, glyceryl monostearate, kaolin and combinations thereof.

29. A dry powder preparation suitable for forming a non-toxic, edible, enteric film coating according to claim 1, wherein the tack reducing agent is selected from the group consisting of talc, aluminum hydrate, glyceryl monostearate, kaolin and combinations thereof.

30. The method of claim 24, wherein the tackifier is selected from the group consisting of talc, aluminum hydrate, glycerin monostearate, kaolin, and combinations thereof.

31. The method of claim 26, wherein the tackifier is selected from the group consisting of talc, aluminum hydrate, glycerin monostearate, kaolin, and combinations thereof.that the tackifier is selected from the group consisting of talc, aluminum hydrate, giloenn monoester, kaolin and combinations thereof. or the process according to claim 26, wherein the tackifier comprises 5-40 wt.%. glazed OÖCÓU.S. wlzihus s szmó -íom ésdsséu, «zO kééy «. e«;5ŲZ Ss. UsU>yíU?,