GB1583034A

GB1583034A - Coating pharmaceutical cores

Info

Publication number: GB1583034A
Application number: GB1258477A
Authority: GB
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 1976-03-26
Filing date: 1977-03-25
Publication date: 1981-01-21
Also published as: FR2345145B1; CH631620A5; DE2612889B1; FR2345145A1; DE2612889C2; JPS52117415A

Abstract

The coating composition for moulded pharmaceutical articles for the production of a water-insoluble film of a water-insoluble, carboxyl group-containing copolymer is present in the form of an aqueous solution. The coating composition comprises a copolymer which contains 80 to 95% by weight of a vinyl monomer and 5 to 20% by weight of a polymerisable unsaturated mono- or dicarboxylic acid. The aqueous solution additionally contains an amount which is completely or partially equivalent to the carboxyl groups present of an easily volatile base and optionally of a non-volatile base.

Description

(54) COATING PHARMACEUTICAL CORES (71) We, BASF AKTIENGESELLSHAFT, a German Joint Stock Company of 6700 Ludwigshafen, Federal Republic of Germany, do hereby declare the invention, for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following Statement: The present invention relates to a process for coating pharmaceutical cores with film of a water-insoluble copolymer containing carboxyl groups; the coating being insoluble in water but soluble in intestinal juices.

A number of polymers can be used for applying thin coatings to pharmaceutical cores; these polymers are applied either as a solution in organic solvents or as a dispersion in water. Disadvantages in using coating agents which have to be dissolved in organic solvents are that a large amount of expensive solvent is required, that the apparatus needed is more expensive since it has to be explosion-proof, and that expensive measures have to be taken to protect the environment. Disadvantages of using dispersions such as are described, for example, in German Published Application 2,135,073 are that the said dispersions frequently exhibit insufficient stability on storage, and that there must be, if desired, additional precautionary measures for maintaining the stability which have to be observed when working with other conventional auxiliaries for film coating. Furthermore, due to having been manufactured by dispersion polymerization, the polymer dispersions contain a stabilizer and residues of the polymerization initiators used.

U.S. Patent 3,896,108 discloses that an aqueous solution of carboxyalkylcellulose, neutralized by means of alkali or ammonia, may be used for coating pharmaceutical cores. Carboxymethylcellulose has the disadvantage that it gives a clear solution only at relatively low temperatures, of about 5"C, and is insoluble even at room temperature.

In aqueous solution, a great increase in viscosity, due to thickening-up or gelling, occurs even at room temperatures. As a result of this gelling effect difficulties can arise in the conventional coating processes which, with aqueous solvents, are as a rule carried out at from 35 to 60"C.

We have found that good results can surprisingly be achieved by coating the pharmaceutical core using a film-forming coating composition which comprises a copolymer consisting of from 80 to 95% by weight of vinyl acetate and from 20 to 5% by weight crotonic acid, the copolymer being present in an aqueous solution which contains an amount of ammonia which is completely or partially equivalent to the carboxyl groups present in the polymer, the ammonia being volatilized at not more than 60"C to give the coating film. By using the volatile base ammonia, it is possible to drive this off, during the coating operation, by heating to not more than 60"C in order to obtain the water-insoluble polymer directly without the need for a separate acidification step. It is surprising that ammonia is so readily driven off under such circumstances. Vinyl acetate is used in an amount of from 80 to 95%, preferably from 90 to 95%, by weight, based on total weight of monomers, in the copolymers.

Correspondingly crotonic acid is used in an amount of from 5 to 20%, preferably from 5 to 10%, based on total weight.

These binary copolymers are water-insoluble in their free acid form but dissolve in water when base is present.

A particularly preferred coating composition contains a copolymer of 90% of vinyl acetate and 10% of crotonic acid, by weight.

The above copolymers advantageously have K-values of from 20 to 50, preferably from 35 to 40. The K-values are determined by the method of Fikentscher, Cellulose Chemie, 13 (1932), 58 - 64 and 71 - 74, in 1% strength solution in dioxane at 20"C; K = k. 103.

It is surprising that, on applying an aqueous solution of copolymer to be used according to the invention onto a pharmaceutical core, a water-insoluble homogeneous smooth film, which has a slight gloss, can be achieved if the aqueous sol ution contains an amount of ammonia, which is completely or partially equivalent, as a rule equivalent to from 75 to 100%, and preferably completely equivalent, to the carboxyl groups present in the polymer.

The film-forming coating composition may be applied by conventional means known to those skilled in the art; advantageously, processes of film-coating in a kettle, using spray embodiment, or manual application, or modified spraying using the dipleg process, or film coating in a fluidized bed using a Glatt fluidized bed granulator, are employed. Such conventional processes are described, for example, in R. Voigt, Lehrbuch der pharm. Technol ogle, 1975, Verlag Volk und Gesundheit, Berlin.

In general, the coating composition is used in the form of aqueous solutions of from 2 to 10% strength by weight, based on total weight of the solution.

To produce the coating, the process is advantageously carried out at from 35 to 60 C. Surprisingly, the ammonia is removed with the water solvent even at temperatures as low as this when vinyl acetatelcrotonic acid binary copolymers are used.

The properties of the film coatings can be modified by adding other water-soluble compounds, so that the entire range, from coatings resistant to gastric juices up to water-soluble coatings, can be produced.

For example, film coatings which dissolve or swell in gastric juices or water and release the active compounds, as described, for example, in German Published Application 1,617,351, may be obtained by adding water-soluble polymers.

Water-soluble or swellable coatings may also be obtained by adding water-soluble polymers, for example polyethylene glycol of molecular weight from 400 to 6,000 or polyvinylpyrrolidone of molecular weight from 25,000 to 40,000. The said polymers are employed in amounts of from 1 to 10%, based on the amount of copolymers employed.

Water-insoluble additives, e.g. talc, titanium dioxide and colored pigments, may also be added to the copolymer solutions, in the conventional way.

The finished coated pharmaceutical cores obtained according to the invention are in general from 5 to 10% heavier than the original cores, but completely continuous coatings of satisfactory appearance can be obtained by applying an amount which is as little as from 2 to 3% of the weight of the core.

The polymers to be used according to the invention may be manufactured by conventional methods, e.g. suspension b ead polymerization initiated by free radicals, and the relevant processes may be found in the literature, e.g. Präparative Pharmazie, 6 (1970), 149- 154. The following Examples illustrate the invention. In the Examples a conventional temperature range of 35 to 60"C was used for the spraying at which temperature the ammonia was removed along with water from the sprayed in solution leaving the coating of polymer.

EXAMPLE 1 200g of a copolymer of vinyl acetate and crotonic acid (in the weight ratio of 90:10), having a K-value of about 36, are dissolved in 4,200g of demineralized water, with the addition of 14g of concentrated ammonia.

The aqueous solution, which has a pH of 7, is then applied to the pharmaceutical cores, by spraying in a fluidized bed. A smooth, colorless coating is obtained.

EXAMPLE 2 Composition of the coating suspension: 13.5g of a copolymer of vinyl acetate and crotonic acid (in the weight ratio of 90:10), having a K-value of about 36, 6.5g of talc, 10.0g of titanium dioxide, 9.0g of pigment, e.g. L-Rotlack 87230 N (manufactured by Siegle, Stuttgart) and 361g of water.

The copolymer is dissolved by stirring in 300g of demineralized water containing 0.8ml of concentrated ammonia. The solids, worked into a paste with 61g of water, are added to the neutral solution and are thoroughly mixed in, using a suitable stirrer.

When the suspension is applied to pharmaceutical cores (2kg = 12,000 moldings) by spraying in a Glatt fluidized bed granulator, uniformly colored, continuous coatings are obtained.

EXAMPLE 3 Composition of the coating suspension: 30g of a copolymer of vinyl acetate and crotonic acid (in the weight ratio of 90:10), 3g of polyvinylpyrrolidone of K-value 25, 9.75g of talc, 15.00g of titanium dioxide, 13.50g of a pigmented vehicle and 528.75g of water.

The copolymer is dissolved in 150ml of demineralized water containing 2.25ml of concentrated ammonia. The aqueous suspension of the solid constituents is added to the neutral solution, and the resulting suspension is homogenized by means of a stirrer and is applied to the pharmaceutical cores by spraying in a fluidized bed. The suspension has a solids content of 11.8%.

EXAMPLE 4 Composition of the coating suspension: 13.5g of a copolymer of vinyl acetate and crotonic acid (in the weight ratio of 90:10) having a K-value of about 36, 6.5g of talc, 10g of titanium dioxide, 9.0g of pigments, 3g of polyethylene glycol 400 and 358g of water.

The coating suspension is prepared as described in Example 2. The film coating is then applied to the pharmaceutical cores by spraying in a fluidized bed.

WHAT WE CLAIM 1S: - 1. A process for producing a film of a water-insoluble polymer on a pharmaceutical core, wherein the core is coated with a copolymer consisting of from 80 to 95% by weight of vinyl acetate and from 20 to 5% by weight of crotonic acid, which copolymer is water-soluble in the free acid form, by applying a coating composition in the form of an aqueous solution which contains an amount of ammonia which is completely or partially equivalent to the carboxyl groups present, in addition to the copolymer, and volatilizing the ammonia at not more than 60"C to form the waterinsoluble polymer on the core.

2. A process as claimed in claim 1, wherein the aqueous solution contains ammonia in an amount equivalent to from 75 to 100% of the carboxyl groups present.

3. A process as claimed in claim 1 or 2, wherein the coating process is carried out from 35 to 60"C, the ammonia being removed with the water during the coating.

4. A process as claimed in any of claims 1 to 3, wherein the aqueous solution is applied by spraying in a fluidized bed.

5. A process as claimed in any of claims 1 to 4, wherein the polymer contains 5 to 10% by weight of crotonic acid units.

6. A process as claimed in any of claims 1 to 4, wherein the copolymer consists of vinyl acetate and crotonic acid in the weight ratio of 90:10.

7. A process as claimed in any of claims 1 to 6, wherein the aqueous solution additionally contains from 1 to 10% by weight, based on the copolymer in the coating composition, of a water-soluble polymer.

8. A process as claimed in any of claims l to 7, wherein the copolymer has a K-value of from 20 to 50.

9. A process as claimed in any of claims 1 to 8, wherein the aqueous solution contains from 2 to 10% by weight of the copolymer.

10. A process as claimed in any of claims 1 to 9, wherein from 2 to 10% by weight of coating is applied to the core.

11. A process as claimed in claim 1 carried out substantially as hereinbefore described or exemplified.

12. Pharmaceutical cores which have been coated with a water-insoluble coating by a process as claimed in any of claims 1 to 11.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. described in Example 2. The film coating is then applied to the pharmaceutical cores by spraying in a fluidized bed. WHAT WE CLAIM 1S: -

1. A process for producing a film of a water-insoluble polymer on a pharmaceutical core, wherein the core is coated with a copolymer consisting of from 80 to 95% by weight of vinyl acetate and from 20 to 5% by weight of crotonic acid, which copolymer is water-soluble in the free acid form, by applying a coating composition in the form of an aqueous solution which contains an amount of ammonia which is completely or partially equivalent to the carboxyl groups present, in addition to the copolymer, and volatilizing the ammonia at not more than 60"C to form the waterinsoluble polymer on the core.