US2314527A - Method of making sealed capsules - Google Patents

Description

March 23, 1943. H.'F. TAYLOR I METHOD OF MAKING SEALED CAPSULES 'Filed July 6, 1940 I INV ENT OR.

ROE/V F. TA no? BY M Patented Mat. 23, 1943 METHOD OF MAKING SEALED CAPSULES Harden F. Taylor,l\lew York, N. Y., asslgnor to The Atlantic Coast Fisheries Company, New York, N. Y., a corporation of Maine Application July 6, 1940, Serial No. 344,215

3 Claims. (Cl. 226-41) This invention relates to a method of making capsules filled with a medicament. More particularly, this invention relates to a method of making sealed capsules containing a solid medicament surrounded by an inert gas.

In my Patent No. 2,183,053, there is disclosed a vitamin preparation comprising dry beadlets in which a colloidal substance, preferably gelatin, and with or without a plasticizer, constitutes a continuous phase matrix having discrete particles of a vitamin-bearing liquid dispersed therein and completely imprisoned and surrounded thereby whereby no free vitamin-bearing liquid is on the exterior surfaces of said beadlets. These beadlets are of a relatively small size, i. e. from .01 to 1.0 mm. in diameter, and thusa number of these beadlets are necessary to provide an individual dosage.

I have found that an individual dosage can be obtained by filling an ordinary two-piece dry gelatin capsule withthe quantity of beadlets necessary to constitute the' dosage. Since the beadlets are spherical in shape, they do not completely occupy the space in the capsule and the interstitial spaces are ordinarily filled with air. 'I'his is true irrespective of whether the capsule is filled with beadlets alone or with a mixture of beadlets and other particles (powdered or subdivided) of solid medicaments, such as vitamin B complex, liver extracts or other substance or substances which may or may not be themselves labile or oxidizable. In any event, I have. found that it is highly desirable to exclude substantially all the air normally inside the capsule and filling the interstitial spaces, and to substitute an inert gas in place and stead of said air.

An object of this invention is to provide a method of making a capsule filled with a solid medicament, i. e. beadlets alone or in admixture with other powdered or other sub-divided medicaments, and in which the spaces are substantially free of air and filled with an inert gas.

Other objects will appear from .the following description, appended claims, and accompanying drawing wherein:

Figure l is an enlarged vertical section of a capsule contemplated by this invention.

Referring now to the drawing, wherein there is shown a filled capsule prepared in accordance with this invention and wherein like reference numerals designate like parts, the reference numeral i designates a dry gelatin capsule which is filled with a solid medicament, such as gelatin beadlets 2. The size of the capsule i is such that when filled, it will contain sufilcient beadlets or other medicament, or both, to constitute an individual dosage. As further shown in the I drawing, the capsule is formed of a bottom member 3 which is designed to be telescopically engaged by the cap I.

The interstitial spaces between the beadlets, as well as any other spaces in the capsule, are substantially free of air or oxygen and are filled with an inert gas. In other words, an inert gas constitutes the gaseous medium within the capsule.

The invention is not restricted to any particular inert gas. Any inert'gas which is non-toxic in the amounts employed may be used. Nitrogen and carbon dioxide are illustrative examples of inert gases which have given satisfactory results.

The capsule is provided with means to inhibit separation between the bottom member 3 and the cap I and also inhibit leakage of the inert gas from the interior of the capsule. This isobtained by securing the bottom member 3 and the cap 4 together. Though this may be obtained in various manners, I prefer to adhesively apply a sealing band 6 around the capsule so that it will be united to both the cap 4 and bottom member 3 to seal the same-and at the same time envelop the annular edge 'I of the cap 4. The sealing member 6 preferably consists of gelatin of the type employed in making the capsule.

To produce filled capsules of the type and nature contemplated by this invention and hereinbefore described, empty bottom members 3 of the capsules i are filled with the beadlets 2 in any convenient manner, and thereafter the caps 4 are applied in the usual manner. It is to be noted that at this stage of the process, air constitutes the gaseous medium within the capsules and also fills the interstitial spaces. In accordance with the principles of this invention, the thus-filled capsules are then treated to remove the air from within the capsules and introduce in place and stead thereof an inert gas.

In one embodiment of the process, the capsules filled and capped as previously explained are introduced into a chamber which is thereafter hermetically sealed. The air is then withdrawn or exhausted from the chamber whereby the air within the capsules is also. withdrawn or exhausted. The production of the vacuum. just described, is produced in such a manner as 'not, to cause the air within the capsules to expand suddenly and thereby blow off the caps; I have found that if the air in the chamber is pumped out slowly and gradually, the air content in each capsule will have time to escape therefrom through the joint formed by the overlapping portions of the bottom member 3 and the cap 4 without producing any deleterious effects.

Although a moderate or even a high vacuum may be established, I prefer to produce a vacuum of about 1 mm. of mercury.

After the desired vacuum has been obtained, the selected inert gas is introduced into the chamber and the pressure in the chamber is permitted to build up to at least atmospheric pressure. The inert gas within the chamber leaks into the capsules through the joint formed by the overlapping portions of the cap and bottom member. The capsules are maintained within the chamber until equilibrium has been established between the interior and exterior of the capsules.

It is, of course, practical to raise the inert gas to super-atmospheric pressure during the introduction of said inert gas into the interstitial spaces within the capsules. When such a procedure is employed, after the pressure has been built up to the desired degree it is slowly released from the chamber to establish atmospheric pressure therein, whereupon some of the inert gas escapes from the capules to establish atmospheric pressure therein.

It is obvious that a minute trace of oxygen may remain mixed with the inert gas inside the capsules. If extreme de-oxygenation is desired, the capsules filled, as previously described, with inert gas may again be subjected to a high vacuum whereby the inert gas is withdrawn from the capsules, after which the inert gas may be admitted under pressure, as previously described. The completeness of the removal of oxygen can be carried to any desired degree, ranging from .that obtained by a single exhaustion of the original air to moderate vacuum and admission of inert gas to atmospheric pressure, to the other extreme of providing an extremely high vacuum, admitting inert gas under pressure and repeating these operations two or more times.

If desired, means may be provided to restrain and prevent the caps from beingblown of! the capsules on repeated exhaustion. A simple arrangement is one in which the filled capsules are positioned parallel to each other and with their two ends near to or in contact with restraining members which prevent the caps from being blown on during exhaustion. These restraining means may be embodied in a foraminous or pervious tray or other holder on which the capsules are disposed in the chamber during the exhaustion of the air and the introduction of the inert gas.

After the capsules have been treated as previously described and the interstitial spaces therein filled with the inert gas, they are appropriately sealed. To seal the capsules, a narrow strip of gelatin constituting the sealing band, preferably after having one side thereof energized with mo sture, is wound around the capsule to envelop the annular edge of the cap and unite itself to both the cap and bottom member. Alternatively, a solution of gelatin may be applied to the previously-mentioned areas of thecapsules in any convenient manner and thereafter dried. Instead of gelatin, any other suitable non-toxic substance may be employed to seal the capsules .as described.

Though the invention has been specifically described in connection with beadlets, it is to be understood that this is for purpose of illustration and that the invention is not restricted thereto. The invention is equally applicable to any solid medicament, and preferably those which are labile or oxldizable, or mixtures thereof.

The term particles of a solid" as used in this description and following claimsis intended to cover a substance which is per se small in size, as for example beadlets, or a substance which has been obtained by powdering or otherwise sub-dividing a solid.

Since it is obvious that various changes and modifications may be made in the above description without departing from the nature or spirit thereof, this invention is not restricted thereto except as set forth in the appended claims.

I calm:

1. A method which comprises exhausting the air from the interior of a two-piece gelatin capsule formed of telescopically engaging bottom and cap members and filled with particles of a solid medicament while the ends of said capsule are restrained to prevent the cap from being blown off, introducing an inert gas into the interior of said capsule to fill the spaces including the interstitial spaces thereof, and sealing said cap and bottom members together.

2. A method which comprises introducing a two-piece gelatin capsule formed of telescopically engaging bottom and cap members and filled with particles of a solid medicament into a chamber, withdrawing the air from said chamber to produce a vacuum therein while the ends of said capsule are restrained whereby the air in said capsule will be withdrawn through the joint formed by the cap and body member and a vacuum produced therein without blowing off said cap, introducing an inert gas into said chamber until the pressure therein is at least atmospheric whereby said inert gas will be introduced into said capsule through the joint formed by the cap and body member, maintaining said capsule in said chamber until equilibrium is established between the interior and exterior of the capsule, and.thereafter sealing the said cap and bottom members together.

3. A method which comprises introducing a two-piece gelatin capsule formed of telescopically engaging bottom and cap members and filled with particles of a solid medicament into a chamber, withdrawing the air from said chamber "to produce a vacuum therein while the ends of said capsule are restrained whereby the air in .said capsule will be withdrawn through the joint formed by the cap and body member and a vacuum produced therein without blowing off said cap, introducing an inert gas into said chamber until the pressure therein is superatmospheric whereby said inert gas will be introduced into said capsule through the joint formed by the cap and body member, releasing the pressure until atmospheric pressure is obtained, maintaining said capsule in said chamber until equilibrium is established between the interior and exterior of the capsule, and thereafter sealing the said cap and bottom members together.

HARDEN F. TAYLOR.

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