Title:
APPARATUS FOR COATING TABLETS
United States Patent 3841262


Abstract:
Process for coating tablet cores or the like with a film, comprising moving a plurality of tablet cores about within a container, introducing a current of gas through an outlet into said container into the body of moving tablet cores in such manner that a substantially tablet-free gas space is formed just beyond said gas outlet which is surrounded by said moving tablet cores, and spraying a suspension or solution of film-forming material into said current of gas. The process combines the best features of conventional coating processes in a rotating dragee kettle with the advantages of a fluidized bed coating operation.



Inventors:
Groppenbacher, Gregor (Heddesheim, DT)
Rieckmann, Peter (Mannheim-Waldhof, DT)
Rothe, Werner (Hockenheim, DT)
Schalk, Heinz (Mannheim, DT)
Schellhorn, Jurgen (Mannheim-waldhof, DT)
Application Number:
05/260579
Publication Date:
10/15/1974
Filing Date:
06/07/1972
Assignee:
BOEHRINGER MANNHEIM GMBH,DT
Primary Class:
Other Classes:
118/20, 118/24
International Classes:
A23G3/20; A23G3/26; A61K9/28; B05D1/02; (IPC1-7): B05C5/00
Field of Search:
118/19,24,20,303 259
View Patent Images:



Primary Examiner:
Mcintosh, John P.
Attorney, Agent or Firm:
Burgess, Dinklage & Sprung
Parent Case Data:


This is a division of application Ser. No. 152,797, filed June 14, 1971, now abandoned.
Claims:
What is claimed is

1. An apparatus for coating tablet cores or the like with a film, comprising a container for said cores, means for rotating said container about a horizontal or inclined axis, fixed means for introducing a gas into said container immediately adjacent its bottom independently of the rotation of said container thereby to be discharged into the mass of said cores and to form a tablet-free gas space just beyond the point of gas introduction, said container being provided with an outlet for said gas, whereby gas introduced into said container traverses said container on its way to said outlet, and means for spraying liquid into said gas immediately adjacent said point of gas introduction so that said sprayed liquid flows into said container together with said gas and immediately contacts the tablets surrounding the tablet-free gas space.

2. An apparatus according to claim 1, wherein said container is rotated about a horizontal axis.

3. An apparatus according to claim 1, wherein said spraying means comprises a two-component nozzle.

4. An apparatus according to claim 1, wherein said spraying means and said gas introducing means are positioned so as to discharge the liquid and gas in a direction substantially parallel to the bottom of said container.

Description:
The present invention is concerned with a new apparatus for varnishing formed bodies, especially tablets or tablet cores, with film-forming materials and is also concerned with a device for carrying out this process.

The varnishing of formed bodies by means of which an impervious coating is formed from film-forming materials and possibly adjuvants, is a process which is of increasing importance for the pharmaceutical industry. Ordinary tablets, which have been obtained by pressing from pharmaceutically active substances and filling and binding agents, must, for a large variety of reasons, be provided with a coating. The most important reasons are the following:

1. Protection from tablet dust in the case of colored or highly active materials;

2. Masking of an unpleasant taste or odor of the active material;

3. Facilitating swallowing due to a smoother and less absorbent surface of the tablets;

4. Protection of the contents of the tablets by means of a coating which is resistant to gastric juices;

5. Improvement of the appearance of the tablets.

The most important coated tablets are sugar dragees, which are coated with a thick covering layer, and film dragees or varnished tablets, which only have a thin coating. The varnishing of tablets is continuously increasing in comparison with the production of sugar dragees because varnished tablets possess the following advantages:

1. ECONOMIC PRODUCTION;

2. SUBSTANTIALLY SMALLER INCREASE OF WEIGHT AND SIZE;

3. THE PRESERVATION OF PREVIOUSLY PROVIDED SCORINGS AND MARKINGS ON THE TABLETS;

4. INCREASED STORAGE STABILITY REGARDLESS OF CLIMATIC INFLUENCES, AND THUS SIMPLIFICATION OF PACKING.

The varnishing of formed bodies, especially of tablets and tablet cores, is, according to the present state of the art, carried out by one of two principal processes:

1. VARNISHING IN A DRAGEE KETTLE

Drageeing kettles are axially symmetrical vessels which rotate about a horizontal or oblique axis. Consequently, when formed bodies are introduced into a rotating drageeing kettle, they are rolled around. The coating materials are sprayed in the form of aqueous or organic suspensions or solutions on to the moving formed bodies and the solvent or suspension agent is evaporated with a current of cold or warm air.

Whereas when applying a sugar coating the cores must be well moistened with the drageeing suspension in order to achieve a uniform dragee coating, this must normally be avoided in the case of varnishing in order to prevent the cores from sticking together. The rapid distribution of the varnishing suspension by spraying is, therefore, just as necessary as a simultaneous drying. According to Hess and Jansen ("Lackierte Tabletten und Filmdragees", published in Pharmac. Acta Helvetiae, No. 10, 599/1969), the problem is solved by utilizing a very large number, e.g., several hundred to several thousand, short, successive bursts of spray, drying being carried out by blowing in warm air during the intervening periods of time. In this way, the tablets in the kettle never become so moist that they tend to stick together or adhere to the wall of the drageeing kettle.

Important advantages of this process are that the apparatus used is extremely simple and, in many cases, is already available for the production of sugar dragees. Since the throughput depends practically only upon the volume of the kettle, relatively large quantities of formed bodies can be coated relatively easily. The most important disadvantage of this process is the production of spray mists which apply varnish not only to the formed bodies or tablet cores but also to the walls of the kettle, the exhaust pipes therefrom and the surroundings; besides causing an unpleasant contamination, this also results in a loss of up to 50% of the amount of varnish sprayed in and thus gives rise to a considerable increase of the cost.

2. VARNISHING IN A FLUIDIZED BED

In the case of the fluidized bed process a stationary vessel is used, formed bodies present therein being held in suspension and moved about by a current of air. A varnish solution or suspension is sprayed into this fluidized bed and, due to the current of air which holds the formed bodies in suspension, the solvent of suspension agent is simultaneously evaporated off (cf. Zeller, "Lackieren von Presslingen in der Flugschicht", Pharmaz. Industrie, 31, 11/1969).

The advantage of such a technique lies in the rapid drying of the cores as a result of the high throughput of air and in the enclosed working space used which ensures clean operating conditions. However, a disadvantage of the apparatus used is that it is relatively expensive and, in most cases, necessitates new capital investment. Further disadvantages are the high operating costs (use of large amounts of air) with the use of relatively small batches (about 10 - 30 kg.). Furthermore, it has been found that only relatively tough or hard cores can be introduced into such a fluidized bed if the attrition caused by rubbing together of the cores is not to be too great.

It is an object of the present invention to provide a device which combines, as far as possible, the advantages of varnishing in a drageeing kettle with the advantages of the fluidized bed process.

We have now found that this can, surprisingly, be achieved with the use of a conventional drageeing kettle in which the drying air is not, as previously, blown on to the surface of the cores moved about by the rotation of the kettle but is blown in through an immersion tube, which terminates near the bottom of the drageeing kettle, into the middle of the cores and a suspension or solution of film-forming materials is sprayed into the small tablet-free gas space which is established just beyond the mouth of the immersion tube. This space is created by the expressed drying gas which is appropriate in pressure and volume so as not to blast through the tablet cores, in which case the varnish would not be fully utilized before the gas is exhausted, and so as not to permit only a few cores adjacent the mouth to receive too much varnish and adhere to each other with ultimate caking and clogging.

In spite of the comparatively strong current of the drying air, we have found that the spray mists are deposited practically quantitatively on the formed bodies and thus the troublesome contamination of the drageeing kettle and of the surroundings, as well as the loss of the varnishing suspensions or solutions, which are sometimes very expensive, are avoided.

Since the drying air comes into intensive contact with the cores or formed bodies, we have also found that the amount of air can be considerably reduced in comparison with the conventional process and, nevertheless, a more rapid drying is achieved.

For carrying out the process according to the present invention, it is substantially immaterial which varnish formulation is employed so long as it has a viscosity which is sufficiently low to permit efficient spraying thereof. Furthermore, practically all cores and formed bodies can be used which also sufficiently stable under the conditions prevailing in the case of sugar drageeing.

The invention will be further described with reference to the accompanying drawings wherein:

FIG. 1 is a schematic sectional view through a drageeing vessel with one embodiment of gas and liquid inlets in accordance with the invention; and

FIG. 2 is a similar view of another embodiment of gas and liquid inlets in accordance with the invention.

Referring now more particularly to the drawings, both of which show their immersion tubes on a magnified disproportionate scale, the form and arrangement of the immersion tubes can be altered substantially while still being able to fulfill the purpose according to the present invention. On form which has been found to be especially useful is illustrated in FIG. 1 wherein spherical container 10 is mounted with its axis inclined at an angle of about 30° to the horizontal, the container being rotated about its axis by a drive. The container has a gas outlet 11 above the tablets for escape of gas supplied near the container/botton and is mounted so as to be stationary but not to interfere with rotation of the container. The pipe 12 bends inside the container in the same direction as the rotation of the container so that its opening 13, whose plane is substantially vertical, is adjacent the container bottom. Axially of pipe 12 there is a spray nozzle supply pipe 14 which terminates in a nozzle 15 located substantially in the plane of opening 13.

In FIG. 2 the cylindrical container 20 rotates about a horizontal axis and is provided with a gas outlet 21 above the level of the tablet cores. A vertical immersion tube or pipe 22 projects into container 20 and its horizontal opening 23 is widened in the direction of rotation of the container, i.e., counterclockwise. A spray nozzle supply pipe 24 is secured inside pipe 22 and terminates in a nozzle 25 so located that spray therefrom is discharged in the direction of movement of gas discharged through pipe 22.

The process according to the present invention for the varnishing of tablet cores and the like with film-forming materials is, therefore, characterized in that a suspension or solution of film-forming materials is sprayed into a current of drying air which is on all sides surrounded and enveloped by moving tablet cores or the like.

In order to obtain an especially uniform coating, we have found it to be advantageous to conduct the current of drying air, and thus the current of sprayed varnish solution or suspension, substantially in the direction which corresponds to the movement of the cores or the like brought about by the rotation of the container and by the action of gravity.

Whereas in the case of the conventional varnishing process in a drageeing kettle, single-component nozzles are necessary in order to minimize the spray mist, it being necessary, therefore, to operate with spray pressures of up to 150 atmospheres, such spray mists do not have a disturbing effect in the case of the process according to the present invention. Therefore, according to the present invention, there can also be used, with good results, two-component nozzles which can be operated at an atomizing air pressure of only 2 - 5 atmospheres.

It has proved to be especially advantageous that, with the process according to the present invention, the amount of varnish applied to the individual tablet cores or the like can be precisely predetermined. Therefore, highly active materials can be incorporated into the varnish suspension and, nevertheless, can be applied uniformly in precise amounts to the individual tablet cores or the like without waste.

The present invention also provides an apparatus for varnishing tablet cores and the like, this device comprising a container for said cores, means for rotating said container, fixed means for introducing a gas into said container adjacent its bottom independently of the rotation of said container, said container being provided with an outlet for said gas, whereby gas introduced into said container traverses said container on its way to said outlet, and means for spraying liquid into said gas introducing means so that said sprayed liquid flows into said container together with said gas. If desired, the spray nozzle can be constructed as a two-component nozzle. Furthermore, the spray nozzle and the opening of the air inlet can discharge their fluids in a direction parallel to the bottom of the drageeing kettle.

The following Examples are given for the purpose of illustrating the present invention:

EXAMPLE 1

50 kg of scored placebo dragee cores are placed in a drageeing kettle, in accordance with FIG. 1, rotated at 30 rpm about an axis inclined at 30° to the horizontal. The cores have a diameter of 10 mm, a Stokes hardness of 3 kp and an average weight of 333 mg per core.

A tube made of polypropylene with an internal diameter of 8 cm which broadens out via a curve into an end piece of 12 cm diameter, dips into the cores. The air exit opening points in the direction of downwardly directed flow of the cores. In the middle of the air exit opening, there is a two-component nozzle which, for aerodynamic reasons, has a conical shape. The nozzle opening is 1.5 mm. The varnish suspension, which is kept continuously stirred, is supplied without pressure. An atomization pressure of 2 atmospheres gage is used. The immersion tube operates at a rate of 500 m3 /hour and the air is blown in at ambient temperature.

With the use of the above-described device, there is sprayed on to the cores, within the course of 50 minutes, 6000 g of the following varnish suspension:

Eudragit E (12.5%) 300 parts talc 50 parts titanium dioxide RN 56 40 parts yellow varnish ZLT 2 20 parts (FDA approved No. FD+C Yellow 5) polyglycol 6000 10 parts (50% aqueous solution) ethanol 580 parts.

When the application of the varnish is finished, the drageeing kettle is rotated for about another 5 minutes. In this way, a varnish-like gloss is automatically obtained. The average increase of weight is 6 mg/core.

EXAMPLE 2

A varnish solution is applied with an application device similar to that used in Example 1 but with the following alterations:

a. the immersion tube has the form illustrated in FIG. 2 of the accompanying drawings;

b. the nozzle has the shape and arrangement shown in FIG. 2 of the accompanying drawings and has an opening of 1 mm;

c. dry air is applied in an amount of 300 m3 /hour and at a temperature of 20°C.

The varnish suspension applied has the following composition:

ethyl cellulose 60 parts polyvinyl-pyrrolidone 10 parts polyoxyethylene stearate 10 parts carbon tetrachloride 880 parts isopropanol 40 parts

EXAMPLE 3

Into a drageeing kettle, there are placed 50 kg of rod-shaped placebo granules averaging 10 mg in weight, 5 mm in length and 1.5 mm in diameter, and these are then varnished in the manner described in Example 1. However, instead of yellow varnish ZLT 2, there is used the same amount of a brown iron oxide pigment. The amount of varnish applied is 8000 g.

EXAMPLE 4

Using the application apparatus described in Example 1, 50 kg of round placebo cores with a diameter of 10 mm and an average individual weight of 333 mg are sprayed with a varnish formulation of the following composition:

Eudragit L 8000 g Eudragit S 8000 g talc 5800 g white spirit 18200 g

The finished varnished dragees have an average increase of weight of 43 mg. Their disintegration corresponds to the requirements for coatings resistant to gastric juices according to Deutsches Arzneibuch 7th Edition.

EXAMPLE 5

On to 10,000 placebo hard gelatine capsules of oblong form and of size 2 with an average weight of 438 mg, there is applied, in a drageeing kettle, by means of the device used in Example 3, the following varnish solution:

hydroxypropylmethyl-cellulose 42.0 g phthalate diethyl phthalate 12.6 g acetone 365.4 g

The capsules are satisfactorily varnished. The increase of weight per capsule is, on average, 42 mg.

EXAMPLE 6

In the manner described in Example 1, 50 kg of round placebo dragee cores with an average individual weight of 333 mg and a diameter of 10 mm are treated with the following varnish solution:

Eudragit E (12.5%) 300.0 parts talc 49.5 parts titanium dioxide RN 56 40.0 parts yellow varnish ZLT 2 20.0 parts polyglycol 6000 10.0 parts (50% aqueous solution) digoxin 0.5 parts ethanol 580.0 parts.

The average increase of weight is 6 mg/core. The varnish coating of each core contains 0.2 mg digoxin. Analytical determinations according to United States Pharmacopoeia 17, page 198, on 50 varnished dragees give a digoxin content of 0.2 mg. ± 10 percent. Varnishing by means of the process according to the present invention permits a sufficiently accurately measured incorporation of a small amount of an active material into the varnish coating.

Eudragit E employed in the foregoing examples is a cationic copolymer of dimethylaminoethyl methacrylate and lower alkyl methacrylates; Eudragit L and S are anionic copolymers of methacrylic acid and lower alkyl methacrylates, the proportions of monomers differing in the two to modify the water solubility. The polymers are available from Rohm A. G. of Darmstadt, Germany.

It will be appreciated that the instant specification and examples are set forth by way of illustration and not limitation and that various modifications and changes may be made without departing from the spirit and scope of the present invention.