FI87624B - VATTENDISPERSION AV ETT BELAEGGNINGSAEMNE FOER CEILING MODEL OCH FOERFARANDE FOER FRAMSTAELLNING AV ETT CEILING PREPARATION - Google Patents

Abstract

1. Aqueous dispersion of a coating composition for medicaments, comprising dispersed latex particles A) of a carboxyl group-containing polymer which is water-soluble at between pH 5 and 8, and B) a water-insoluble film-forming polymer of high extensibility, characterized in that the weight ratio of the total quantity of latex particles A and B is above 60 : 40 and below 95 : 5.

Description

1 87624 Aqueous dispersion of a coating for a medicinal product and a process for the preparation of a medicinal product

DE-C 16 17 351 discloses a coating material for medicated tablets which contains a water-soluble, film-forming plastic in the form of an aqueous dispersion and a water- or alkali-soluble substance. For gastric fluid-resistant coatings, an alkali-soluble substance is used which dissolves from the tablet coating in an alkaline environment and leaves pores through which the active ingredient can then diffuse. For example, fatty acids are proposed as alkali solubilizers. The release of the active substance begins when the tablet enters an aqueous environment at which the pH-soluble substance dissolves.

It is also known from the same publication to add water-soluble macromolecular substances, such as polyethylene glycol, to the coating, which are soluble regardless of the pH of the environment. The use of alkali-soluble macromolecular agents was not yet known, but it was expected that, like small molecule time-soluble agents, they would cause the coating to penetrate by diffusion at the pH at which they are soluble.

EP-A 52 075 discloses the combination of a dispersed acrylic ester polymer with water-insoluble ethyl ethers. They provide drug coatings that slow the release of the active ingredient.

Application According to DE-A 31 27 237, an aqueous dispersion of a gastric fluid-resistant coating material is combined with polyethylene glycol and polyvinylpyrrolidone to give 2,87624 drug coatings which degrade rapidly in intestinal fluid.

Thiele and Pflegel are in "Pharmazie." 1981, p.

5,858-859 and 1983, pp. 43-45 disclose tackifiers prepared from aqueous dispersions containing 98-99% by weight of a low carboxyl group hydrophobic acrylic / methacrylic ester polymer and 1-2% by weight, in each case based on the total polymerization-10 consisting of acrylic / methacrylic acid and acrylic / methacrylic acid alkyl esters. Although the addition of the latter polymeric material increases the diffusion permeability, it does not cause a rapid release of the active ingredient in the initial range. When more than 2% by weight of hydrophilic polymer is added, the coating becomes unstable. No pH dependence of permeability was observed. Rather, the release of the active ingredient takes place only by diffusion through a non-porous membrane, essentially regardless of pH.

DE-C 21 35 073 discloses drug coating dispersions of polymers containing ·: · 10 to 55% by weight of carboxyl group-containing monomer components. They provide dosage forms for coatings which, even in a weakly alkaline intestinal environment, dissolve rapidly when the carboxyl group content is high and more slowly when the carboxyl group content is lower.

30 Polymers are relatively hard and brittle and slightly stretchable. This can become annoying, for example when compressing granules coated to be resistant to gastric fluid or in a retard form, as the coating can tear and · '. releases the active substance in the stomach too early.

Drug capsules made of these polymers are known from DE-C 21 57 435. By adding plasticizers, such as citric acid esters, the brittleness can be reduced to such an extent that it is possible to make, fill and use the capsules, but still improve the extensibility.

5

EP-B 56 825 also discloses the addition of plasticizers in the preparation of capsules from such aqueous dispersions.

The elasticity and extensibility of durable and retarding drug coatings for manic fluid, which can be prepared from aqueous dispersions, should also be improved without the need to add conventional plasticizers.

The tensile strength of polymer films formed by drying aqueous dispersions of carboxyl group-containing emulsion polymers, as measured by DIN 53 455, has been found to be substantially increased by adding a limited amount of latex of water-insoluble film-forming polymers with higher latex. It can also be observed that the tensile strength increases, which is important above all in the region of a reasonably increased tensile elongation.

1-25 For films formed in different blend ratios from latex blends containing A) a copolymer of 50% by weight of methacrylic acid and 50% by weight of ethyl acrylate and B) a copolymer of 33% by weight of methyl methacrylate and 67% by weight of ethyl acrylate are given in the following measured values for tensile elongation1e (elongation at break calculated from the length of the unstretched space) and tensile strength (tensile at the point of elongation at break): '35 4 87624

Mixture ratio Tensile Tensile strength A: B elongation strength (% N / mm2 dry weight of polymers) _ 10: 0 14 10 9: 1 72 22 8: 2 93 17 7: 3 290 6.2 10 0: 10 600 7.5

Surprisingly, even small additions of a film-forming, highly stretchable polymer substantially improve tensile strength and tear elongation. The addition does not alter the resistance of gastric fluid 15. As without the presence of polymer B, the release of the active ingredient in the gastric fluid can also be easily adjusted as needed by changing the carboxyl content of polymer A rapidly or slowly.

The new coating dispersions are suitable for the preparation of pharmaceutical formulations in which the release of the active ingredient is delayed, in particular those which must bypass the stomach unchanged and release its active ingredient definitively only in the intestine, using an aqueous coating agent. 25 dispersions. Depending on the thickness of the coating, the mixture ratio of the polymers and the other ingredients of the formulation, the release of the active ingredient can then begin in the acidic pH range with diffusion through the intact but more or less permeable polymer layer, after which it rises above pH 5. Finally, when most of the polymer A is dissolved from the mine dressing, the coating disintegrates and releases the drug content.When the gastric release of the active ingredient is less than 5% of the total dose, there is talk of gastric fluid-resistant dosage forms, otherwise products with retardation. When retard formulations are used in other cavities of the body (e.g., rectum, i, 5 87624 vagina, mouth, nose, ear canal) or in the eye or skin, the desired permeability or disintegration of the polymer coating can be adjusted accordingly. to conditions in this range, in particular pH and electrolyte concentration, and if desired can be further stabilized by the use of buffers in the drug formulation.

The carboxyl group-containing polymer (A) is in the form of latex particles dispersed in the aqueous phase. The preparation of such latexes is described in DE-C 21 35 073 and DE-A 31 34 222. However, it is not necessary that the dispersion of this polymer alone form a film. Therefore, hardening comonomers, such as lower methacrylic acid esters, may form a larger portion of the polymer product than if the dispersion were used alone as the coating agent.

The carboxyl group-containing polymer must be water-soluble in at least part of the pH range between 5 and 8, but may still be water-insoluble in the lower part of this range. Because it can be dispersed in water, it must be water-insoluble at least below pH 5. Above pH 8, it is generally water-soluble, but this property is not relevant to the invention. The aqueous dispersion of latex particles ·: · 25 A and B in each case has a pH at which the carboxyl group-containing polymer is insoluble.

In general, the polymer is prepared by radical emulsion polymerization of vinyl monomers in the aqueous phase. Some of the vinyl monomers, preferably 10 to 70, in particular 25 to 55% by weight, contain at least one carboxyl group. Preferred vinyl monomers of this type are acrylic and methacrylic acid, but maleic, fumaric, crotonic or itaconic acid are also useful. The remainder of the vinyl monomers .35 do not contain carboxyl groups and may consist of esters of said carboxylic acids, in particular alkyl esters having 1 to 8 carbon atoms in the 6,87624 alkyl group, acrylic or methacrylonitrile, styrene, α-methylstyrene, vinyl toluene, vinyl toluene, vinyl toluene vinyl acetate. The structure of the emulsion polymer may contain limited amounts of hydrophilic neutralizing comonomers, such as acrylamide, methacrylamide, vinylpyrrolidone, or hydroxyalkyl esters of acrylic or methacrylic acid. They result in a certain diffusion permeability of the coating even at low pH values, 10 which is only desirable in special cases.

The amount of carboxyl group-containing monomers is dimensioned so that the polymer is water-soluble in the pH range of 5-8 and the active ingredient is released at the desired pH. If polymer A is studied alone, then its solubility rate turns out to depend on the carboxyl group content.

Hydrophilic comonomers increase the solubility rate, hydrophobic comonomers slow it down. For the purposes of the invention, water-soluble are considered to be polymers which, in the form of films with a thickness of 20 to 20 [mu] m, are soluble in an artificial intestinal fluid having a pH of 7.5 within a maximum of 60 minutes with moderate mixing. The slowed water solubility in the coatings according to the invention acts by shifting the decomposition point to higher pH values.

25

The solubility rate also depends on the molecular weight. The weight average molecular weight is generally not more than 500,000 and is best between 50,000 and 300,000.

The film-forming polymer (B) is likewise in the form of aqueous dispersed latex particles and is also best formed by radical emulsion polymerization of suitable vinyl monomers. Aqueous film dispersions forming the film are commercially available in large quantities, 35 and their preparation is also well known in numerous publications.

7 87624

Emulsion polymers are referred to as film-forming when they provide a uniform film that adheres securely to the core to be coated under conventional conditions for the use of aqueous drug coating dispersions. Such film formation usually takes place already at room temperature, but a higher drying temperature can also be used. The film-forming polymer is generally selected so that, in the form of an aqueous latex, its minimum film-forming temperature according to DIN 53787 is not more than 60 ° C, preferably not more than 40 ° C. The high extensibility of the film-forming polymer B is essential for the increase in the extensibility of the films formed from polymers A and B. It should be at least 50% at room temperature, preferably above 100%. This requirement is generally met when the dynamic freezing temperature 1a (T5max value, DIN 53445) is not more than 80 ° C, preferably not more than 40 ° C.

Emulsion polymers may be formed from the same vinyl monomers as carboxyl group-containing polymers, but the amount of carboxyl group-containing comonomers is substantially lower or non-existent. Also, hydrophilic comonomers are only polymerized in such a limited amount that the polymer is not water-soluble in the physiological pH range of 1-8 in the gastrointestinal tract. Water solubility only above pH 8 is not an obstacle to the usefulness of the polymer.

High extensibility requires that the polymer 30 structure be rich in "soft" comonomers.

These primarily include alkyl esters of acrylic acid.

They generally form an amount in the range of 40 to 80% by weight of the polymer. Commercial drug release dispersions for the preparation of insoluble coatings for diffusion tablets meet these requirements and are particularly well suited for the purpose of the invention.

The topcoat is conveniently prepared by mixing type A and B latexes in a weight ratio of more than 60:40 to less than 95: 5, preferably between 70:30 and 85:15 by weight of each of these polymer types. It goes without saying that the dispersions to be mixed must be compatible with one another. For example, they must not contain oppositely charged emulsifiers, as this would cause coagulation.

10

The mixture ratio affects the minimum film-forming temperature of the coating agent. It is between the lowest film formation temperatures of the starting latices of polymers A and B. When it is too high, it can be reduced by the addition of film-forming aids which remain in the film either as plasticizers or which leave on drying as a volatile solvent. Examples of such film-forming excipients are ethylene or propylene glycol, glycerin, citric acid esters and polyethylene glycol.

20

As the amount of polymer A increases with respect to polymer B, the rate of release of the active ingredient enclosed in the coated dosage form increases above the pH at which the active ingredient passes through at all. Although at low concentrations of polymer A "'25 the coating membrane is permeable but remains as such, it decomposes at higher concentrations of polymer A immediately after reaching the pH at which it is permeable, especially when the coated core has a disruptive effect due to swelling.

30

Polymers A and B generally comprise from 10 to 40% by weight of aqueous coatings. The rest is water, the emulsifier dissolved in it and any additives.

. In addition to polymers A and B, the coating agent may contain conventional dissolved or suspended excipients and additives. In addition to the already mentioned film-forming auxiliaries, there are, for example, preservatives, thickeners, polishes, dyes and pigments.

The viscosity of the liquid coating agent is suitably between 10 and 1000 cP. Its pH is below 6, usually between 2 and 5.

Coated dosage forms 10

According to the invention, all dosage forms can be coated with the aim of releasing the encapsulated active ingredient at a certain pH. To improve portability, the release of the active ingredient may be slightly delayed over a period of 15 to 60 minutes, or for long-term therapy up to a few months in the body cavities or on the skin.

Objects to be coated may be tablets, granules, pills, granules, crystals, powders, possibly up to 20 gelatin capsules. Granules or pellets can also be prepared using the substances according to the invention after a conventional granulation process. The granules, on the other hand, can be coated or compressed into tablets.

The coating methods correspond to those used with conventional drug coating dispersions. Preferred are container granulation methods in which the coating agent is poured or sprayed onto highly or continuously rotating dosage forms. In this case, warm air is usually blown on for drying.

Preference is also given to the 1-bed process, which is best carried out at an air temperature of 40 to 60 ° C.

However, the drugs can also be embedded in the polymers 35 by dissolving or suspending the active ingredient in the latexes and allowing the mixtures to dry into films, or by coating the polymer films with other drug-containing materials such as paper, textiles, patches, etc. The films can then initially be prepared separately from the drug. and only at a later stage of work put together.

The pH-dependent release is particularly evident in layer thicknesses of 10 to 30. When coating granules, particles and crystals, this corresponds to 10 to 20% by weight of the lacquer coating, in the case of tablets, medicaments or capsules to 3-5% by weight of the lacquer coating, in each case based on the weight of the coated core. Below this range, instead of pH-dependent release, the increasing, time-dependent release through diffusion must be taken into account, and above this range, an increasingly slower release at the pH of the dissolution range.

15 Medicinal capsules

One preferred use of the new dispersions is the preparation of drug capsules. To prepare the capsules, the polished molds are immersed in the dispersion in a manner known per se and, if desired, allowed to drip until the remaining layer forms the desired layer thickness upon drying. The layer is then best dried by rotating the molds in a stream of warm air at 25-50 ° C. The upper edge of the dried layer is cut in the usual way, torn from the mold and in each case two suitably sized parts are pushed together into a capsule. The wall thickness of the capsules or the thickness of the remaining layer after dipping and draining the molds can be influenced by the viscosity of the dispersion. The viscosity can be increased in various ways, namely by raising the pH to the initial swelling range of the carboxyl group-containing polymer A, by adding swellable volatile or non-volatile plasticizers such as ethylene glycol, propylene glycol or. 35 glycerin, or by adding water-soluble high molecular weight thickeners such as cellulose ethers, polyethylene glycols, polyacrylic acid or polyvinylpyrrolidone. With the addition of these 87624 substances, a dispersion is obtained for thixotropic sex. Different types of thickeners can also be used at the same time. The wall thickness of the capsule can also be increased by dipping and drying the molds several times.

5

A second grade capsule can be made by the foil welding method. For this purpose, a uniform layer of dispersion is applied to a rotating heated roll or endless belt and dried to a film of about 50 to 150 μm. When using a roll with embedded cups11a, foils with corresponding embeddings can be made immediately. On the other hand, such dips can be subsequently printed by means of a corresponding pair of rollers at a temperature, for example at 60-100 ° C.

15 These dips are filled with a metered amount of liquid or solid drugs. A second foil, generally made in the same manner, is placed on top and the drug-filled dips are pressed out into individual capsules with a hot tool while simultaneously welding the other 20 or both foils along the edge of the dips.

The manufacture of capsules from a gastric fluid - resistant material is substantially more rational and reliable than the coating of hard gelatin capsules with gastric fluid:. 25 with durable coating.

i ‘Example 1

Preparation of disintegrating tablets * with controlled release of the active ingredient

1440 g of an emulsion polymer of equal parts of methacrylic acid and ethyl acrylate with a dry matter content of 30% and 960 g of an emulsion poly-35 merisate containing 1 part by weight of methyl methacrylate and 2 parts by weight of ethyl acrylate and the substance content is also 30%. Separately, 360 g of 12 7 724 talc were suspended in 2730 g of water, and 18 g of polyoxyethylene sorbitan monostearate (Tween 80) was dissolved in this suspension.

The latex mixture was then mixed with the aqueous suspension 5 and 6 kg of acetylsalicylic acid crystals having a grain size between 0.2 and 0.8 mm were used for coating. For this purpose, the spray suspension was transferred to a storage vessel and fed by means of a hose pump and with constant stirring to an air-operated spray gun. The 10 crystals were then fluidized in a Glatt 1 fluidized bed apparatus (WSG 5) at an inlet temperature of 50 ° C, with warm air flowing from below and a spray gun mounted on top of the fluidized bed with the spray directed downward. The latex mixture was then sprayed on at a spray rate of 33 g / ml to 15 minutes while maintaining a supply of warm air, leaving the exhaust air temperature at about 35 ° C. The application of the varnish had been completed after 170 minutes. For post-drying, warm air was then blown for about 10 minutes in a weak vortex and dried overnight at 40 ° C in a circulating air drying oven.

The coated cores were tested to USP XXI Standard 11a (Paddle Method) at a stirrer speed of 25,100 rpm. The release of the active ingredient was then less than 5% in the artificial gastric fluid within 2 hours. The gastric fluid was then changed to artificial intestinal fluid, pH 6.8. The release of the active ingredient here was more than 75% after one hour and more than 85% after 2 hours.

; Crystals coated with 30,547 g were mixed with 300 g of microcrystalline cellulose (Avicel PH 101) and 150 g of corn starch and 3 g of magnesium stearate and compressed in an eccentric press of about 15 kN into 35 tablets with a diameter of 10 mm and a total weight of 600 mg. These tablets disintegrated in a USP-Paddle at 100 rpm. Within 5 minutes, the i3 87624 undamaged coated particles are released again from contact with the tablet. Release of the active substance in the artificial gastric fluid, as above, less than 5% within 2 hours. After switching to artificial intestinal fluid, more than 75% of the active ingredient had dissolved within one hour and more than 85% after 2 hours.

Example 2 Preparation of controlled release coated particles 150 g of a polymer powder prepared by spray drying an emulsion polymer prepared from equal amounts of methacrylic acid and ethyl acrylate were suspended in 300 g of water and 50 g of water was added dropwise. N sodium hydroxide with stirring. After stirring for a further 30 minutes, the latex formed was mixed with 250 g of an emulsion polymer containing 1 part by weight of methyl methacrylate and 2 parts by weight of ethyl acrylate and having a dry matter content of 30%. Separately, 3.3 g of polyoxyethylene sorbitan monostearate (Tween 80) was dissolved in 750 g of water, 100 g of talc was suspended therein and finally 15 g of acetyl citric acid triethyl ester were further emulsified with stirring.

The latex mixture obtained above was poured into this mixture with stirring and stirred for another 10 minutes to complete the homogenization.

In a laboratory fluid bed apparatus (Uniglatt), 1 kg of cetylsalicylic acid crystals having a grain size between 0.3 and 0.8 mm were fluidized in a 41 ° C air stream and a total of 600 g of spray suspension was added via a hose pump from a spray nozzle mounted in the upper 35 part of the shower facing down. The suspension was then continuously sprayed at a spray rate of 3.5 g / minute with a nozzle diameter of 1 mm and a spray pressure of 1.5 bar. The exhaust air temperature then settled at about 25 ° C and the entire spraying process was complete after 4 hours. The crystals were still fluidized for about 5 minutes in a stream of air and then post-dried overnight in air.

The release of the active ingredient was studied according to Example 1 in a USP-Paddle-1 apparatus: The release in artificial gastric fluid was 2.7% after 1 hour and 4.0% after 2 hours. After switching, the release in the artificial intestinal fluid during the next hour was 62% and after 2 hours 85%.

Example 3 15

Preparation of empty capsules 5.6 g of polyacrylic acid (Carbopol 934 PH) were suspended in 180 g of water, and to this were added and mixed solutions containing 15 g of polyethylene glycol 6000 in 60 g of water and 5 g of polyoxysorbitan monostearate (Tween 8y0) in 10 g. in water. 240 g of emulsion polymer with equal amounts of methacrylic acid and ethyl acrylate and a dry matter content of 30% and 105 g of an emulsion polymer containing 1 part of methyl methacrylate and 2 parts of ethyl acrylate and also having a dry matter content were mixed together. 30%, and mixed with the first preparation. This mixture was transferred to a mixing vessel equipped with a vacuum and a dilute ammonia solution prepared from 10 g of 3 N ammonia and 64 g of water was added dropwise under a reduced pressure of about 250 millibars.

The preparation prepared above was transferred to an immersion tank.

In the manufacture of gelatin capsules, cylindrical VA steel molds were also immersed in the dispersion by a conventional immersion mechanism, which are also conventionally used in the manufacture of hard gelatin capsules, with an immersion time of 3 seconds. The adhered liquid film was then dried at room temperature and about 60% relative humidity. The obtained capsules had a wall thickness of about 200 μm and the dimensions corresponded to a capsule size of 1. To study the resistance of gastric fluid, 250 mg of a 0.3% milk sugar / methylene blue powder mixture was filled into the bottom of the capsule and the capsule was closed by pressing the top. In the gastric fluid resistance study, a study was performed within 10 2 hours in artificial gastric fluid (0.1 N hydrochloric acid) on a USP degradation tester. During this time, only slight swelling of the capsule wall was observed without the liquid penetrating the capsule or disintegrating. After the next exchange, the contents of 15 intestinal fluid BP 80, pH 6.8, were released within 15 minutes, and after 60 minutes the entire capsule wall had disintegrated.

Example 4 20 Making Matrix Tablets s up r a_pu r i s t uk s e 11 a

A spray-dried powder was prepared from a 7: 3 mixture of an emulsion polymer containing 70 parts of methacrylic acid and 30 parts of acrylic acid methyl ester and a 7: 3 mixture of neutral emulsion polymer used in Example 1.

. . . With 170 g of this polymer powder, 600 g of theophylline and 100 g of microcrystalline cellulose (Avicel PH 102), 20 g of talc (DAB) and 10 g of magnesium stearate (DAB) were mixed and compressed at 18 kN into matrix tablets with a diameter of 12 mm and weight 450 mg. This corresponded to 300 mg of theophylline per tablet.

These tablets were monitored in a USP disintegration tester for 8 hours in phosphate buffer, pH 5, and the release of active ingredient 35 was measured. During this time, the tablets disintegrate in part due to the slow erosion of the surface and continuously release the active ingredient at a rate of 15-20% of the active ingredient dose per hour.

Example 5 400 g of a latex mixture prepared from the emulsion polymers of Example 4 in a ratio of 85:15 and having a polymer dry matter content of 15% were added in a forced mixer to a mixture of 400 g of diprophylline and 129.8 g of calcium hydrogen phosphate (Emcompress). The moist mass was pressed through a sieve with a hole width of 1.5 mm, the formed granulate was dried overnight at 40 ° C in a warm air drying oven to a residual moisture content of less than 2% and sieved once more through a sieve with a hole width of 1.5 mm. Thereafter, tablets were compressed from this under normal production conditions after the addition of 6.6 g of talc and 3.6 g of magnesium stearate. The extrudates had a diameter of 12 mm, a breaking strength (Pharmatest PTB type 301) of 150 N, and a total weight of 600 mg corresponding to 400 mg of diprofyl-20 line per single dose. In the USP-Paddle, these tablets showed slow swelling and disintegrated within 4 hours. During this time, the active ingredient was released at a rate of 25-30% of the active ingredient dose per hour.

..25 Example 6 67 g of a latex mixture of the emulsion polymers of Example 1 (ratio 9: 1) (dry matter content 30%) are mixed with 190 g of purified water, mixed with 300 g of finely divided theophylline powder (particle size less than 110 pm) and further processed according to Example 5.

The dry granulate was mixed with: 24 g of microcrystalline cellulose (Avicel PH 102), 4 g of talc and 2 g of magnesium stearate.

17 87624 This granulate mass is compressed into tablets weighing 350 mg, having a breaking strength of 110 to 150 N and a diameter of 10 mm.

In USP-Dissolutions Test 1 in Method 5 (Paddle), these tablets release about 30% of the administered dose in artificial gastric fluid after 2 hours, whereas in the next 3 hours after switching to artificial intestinal fluid, pH 6.8 (BP 1980), more than 90% of the total theophylline has gone into solution.

10

Example 7 with 176.3 g of a latex mixture (dry matter content 30%) with a 60:40 ratio of emulsion polymers prepared on the one hand from equal parts of methacrylic acid and ethacrylic acid and on the other hand 1 part by weight of methacrylic acid methyl ester and 2 parts by weight part of acrylic acid ethyl ester, 35 g of a 20% aqueous solution of polyethylene glycol 6000 and 140 g of purified 20 g of water are mixed evenly, and 3.2 g of tranylcypromine sulfate are dissolved therein.

This batch is applied through a 0.1 mm sieve to a flat surface with an area of 1085 cm 2 and dried at room temperature in a convection oven. A film about 500 μm thick is obtained, which contains 3 mg of active ingredient per cm 2.

In a release experiment using a buffer solution of pH 5.5 (8.82 g NaH 2 PO 4 .H 2 O and 0.39 g Na 2 PO 4 per liter) at 34 ° C, the active ingredient was released from this membrane in the following manner, slowed down as follows: after 12 hours 0.7 mg / cm2 after 24 hours 1.0 mg / cm2 after 40 hours 1.4 mg / cm2.

Such pharmaceutical preparations are particularly suitable for use on the skin.

35 is 87624

Example 8

Immersion of the active ingredient powder by welding 5 A film was prepared from the dispersion mixture described in Example 3. The film had a thickness of 400 μm and was cut into 160 mm wide strips. These films were treated in a deep drawing machine as follows: Ellipsoid depressions were formed from a flat foil with compressed air at about 6 bar at 80-100 ° C and filled with about 200 mg of the milk sugar-methylene blue mixture described in Example 3. A similar flat foil was placed under it and the filled recesses were welded with it at a temperature of about 100 ° C under pressure along the edge and pressed out. Welded capsules 15 have the following release properties when tested by the method described in Example 3: No fluid penetration in the artificial gastric fluid for more than 2 hours and release of the capsule contents after up to 10 minutes, capsule wall disintegration after up to 40 minutes.

Example 9

Coating of tablets'. 25

The latex mixture prepared according to Example 1 was mixed with the talc suspension described in this example. 10 kg of acetylsalicylic acid tablets with a diameter of 12 mm and an active ingredient content of 500 mg each were sprayed continuously in a granulation vessel at 30 rpm. at the rotational speed of the above suspension by supplying warm air (40-50 ° C) using a compressed air spray gun with a nozzle diameter of 1 mm and a spray pressure of 1.2 bar. The spraying time was a total of 3.5 hours-35 hours. The tablets were dried overnight in air at room temperature. The thickness of the coating layer was 5-20 μm.

Claims (8)

An aqueous dispersion of a coating for a medicament containing dispersed latex particles 5 A) a water-soluble carboxyl group-containing polymer with a pH between 5 and 8, and B) a water-insoluble, high-stretch film-forming polymer, characterized in that the total weight ratio of the latex particles A and B is more than 60:40 and less 95: 5. Aqueous dispersion according to Claim 1, characterized in that the polymers A and B are emulsion polymers of vinyl monomers. 15 Aqueous dispersion according to Claim 2, characterized in that the carboxyl group-containing polymer contains from 10 to 70% by weight of acrylic and / or methacrylic acid units. 20 Aqueous dispersion according to Claim 2 or 3, characterized in that the polymers A and B contain units polymerized according to the alkyl esters of acrylic and / or methacrylic acid. Aqueous dispersion according to one of Claims 1 to 4, characterized in that the dynamic freezing temperature of the film-forming polymer is between 10 and 60 ° C. . Aqueous dispersion according to one of Claims 1 to 5, characterized in that the content of polymer A and B is from 10 to 40% by weight. Use of an aqueous dispersion 35 according to any one of claims 1 to 6 for coating a medicament. 20 «7 624 A process for preparing medicaments coated with a gastric fluid-resistant or retardant coating by coating with an aqueous drug coating dispersion and drying, characterized in that an aqueous dispersion according to any one of claims 1 to 6 is applied. 2i 87624