US2552027A - Casting gelatin tablets - Google Patents

Description

y 8, 1951 J. c. BIRD ETAL 2,552,027

CAST ING GELATIN TABLETS Filed Jan. 1'7, 1948 INVENTORS Jfi/WY 6.5m: zwzopa/Pz a. POCHOW,

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ATTORNEY Patented May 8, 1951 CASTING GELATIN TABLETS John 0. Bird, Pleasantville, N. Y., and Theodore G. Rochow, Darien, 'C0nn., assignors to American Cyanamid Company, New York, N. Y., a corporation of Maine Application January 17, 1948, Serial No. 2,938

1 Claim. 1

With the advance in the progress of science it has become desirable to administer various therapeutic agents to both man and animals. Various methods of administration are used among the most eflicient of which is to incorporate the various agents in a matrix and administer separate portions orally, as desired.

In the past gelatin has been used as such a matrix and in the gelatin has been dispersed various therapeutic agents particularly vitamins. I-Ieretofore, considerable difficulty has been encountered because gelatin in its plastic state is so sticky that it is extremely diflicult to handle and a large number of various forms of molds have been used. In the past a standard method was to form temporary cavities in powdered starch, cast the gelatin tablets in the starch and then coat the tablets with clear gelatin by dipping in such fashion that the liquid gelatin in the dipping process did not come in contact with the supporting members.

The starch molds could be used for only one molding cycle and thus costly and time-consuming, mold-making facilities were required as part of the gelatin-forming process. Moreover, the gelatin tablets were left with a coating of starch particles, requiring the extra step of dipping into liquid gelatin.

It is an object of the present invention to provide a method whereby various matrices particularly those containing gelatin may be cast in molds made of Teflon.

It is an object of this invention to provide a method whereby pharmaceutical substances may be incorporated into a matrix which is cast into an individual dose tablet in such quantities as .may be desired.

It is a further object to provide a method whereby gelatin tablets may be rapidly and readily cast in final form without additional treatment. To more particularly illustrate and describe the invention the accompanying drawings and specification show certain embodiments thereof; additional objects and advantages will become apparent in connection therewith.

In the accompanying drawings:

Figure 1 shows a front elevation of a castin machine. I

Figure 2 shows a top view of a single mold cavity.

Figure 3 shows a sectional view of such a mold cavity containing a cast tablet.

Figure 4 shows a series of such molds arranged in a continuous strip.

of polytetrafluoroethylene.

in the literature and in the patents of others, as set forth for example, in Patent No. 2,230,654,

to Roy J. Plunkett, February 4, 1941. The material has a waxy appearance and is comparatively hard, usually of a light grayish color, may be cut, turned and worked more readily than brass and may be cut and worked on either metal or woodworking machinery. The material may be burnished and polished until highly reflective, until almost a specular finish is obtained. The mold, itself, may be molded from Teflon by the methods of Patent 2,400,091 to Alfthan, or otherwise constructed. This mold is more particularly shown in Figures 2 and 3 and may consist of a round member and may be turned from bar stock. It contains a cavity 2 which may be formed by an appropriately shaped drill and polished and burnished by means of successively .finer emery cloths or burnishing dust.

It is considered desirable that the bottom portion of this mold cavity 2 be formed so as to match in curvature thatform produced on the upper face by the surface tension of the material to be cast, so that the final tablet is symmetrical. Whereas various or any desired form of cavity may be used, for pharmaceutical purposes a symmetrical tablet is more acceptable to the trade and accordingly, if the mold cavity 2 is shaped appropriately as shown in Figure 3, the tablet will possess the same curvature on each side, being symmetrical and with a high finish gloss or sheen without further treatment or effort. If desired, for special purposes, a totally enclosed mold may be used, and any desired shape tablet molded.

Figure 1 shows a device which is suitable for casting these individual tablets. The gelatin mixture prepared as described below, is shown at 4. This mix is placed in a vessel 5 which is surrounded by a jacket 6 or other heating means whereby hot water or other heat transfer medium may be used to maintain the desired tern perature control. The cover l2 may be provided with a filler tube 20, or other suitable filling means. Electrical elements and electric control are very satisfactory in a properly insulated kettle.

In Figure 1 are shown entrance 1 and exit 8 pipes for the thermally conditioning fluid. The interior of the kettle is shown with a stirrer 9 to insure the homogeneity of the mix. This stirrer may be driven for example by a gear wheel i and worm l l or by other suitable means which may be in turn supported by the cover l2 for the kettle. The cover is held in position by any suitable means. Through the axis of this wheel and kettle is shown a plunger I3 which is reciprocable by means of an adjustable eccentric l4 so that this plunger is adjustably raised and lowered in a time adjustable fashion. If the temperature is kept constant as the plunger raises and lowers, a uniform portion of the mix is trapped in the plunger cylinder i 5 which in turn acts as a pump casing thereby ejecting a uniform portion of the mix from the kettle through the orifice 16 with each functioning stroke of the plunger. The exit orifice l6 and the plunger itself may be made from Teflon to insure that the gelatin mix will not stick to and jam the measuring mechanism. The individual mold is supported by a carrier 11, the design of which depends upon the number, size and other conditions of the tablets to be cast. The adjustable eccentric may be either manually or mechani- 'cally operated and the molds on their support carrier I! either manually or mechanically operated and indexed so that a separate mold is positioned under the orifice with each stroke of the plunger, thereby providing a separate mold for each tablet. For large scale production a continuous strip, as shown at l8, may be used containing any desired number of mold cavities l9 K which may be filled by an individual plunger or by a gang of plungers arranged to operate in suitably timed relationship.

In one particular modification individual Teflon molds were prepared from a rod of Teflon 1.9 cm. in diameter by cutting into discs .9 cm. high. Cavities were bored out by means of a specialboring tool, giving the cavity a depth of 3 mm, with an elliptical bottom. The bored cavity'was polished using a mandrel with a corresponding shape, finishing it with a cloth charged with an aqueous suspension of powdered emery; progressively finer emery being used until a specularly smooth surface was obtained. Such a polished cavity lasts indefinitely as the gelatin will not stick to it, and it remains clean and untarnished.

Other measuring mechanisms maybe used and other devices or arrangements constructed whereby uniform individual portions of gelatin are ejected into individual mold carriers. Various mechanical means will suggest themselves whereby the manual or mechanical operations may be eased for the operator provided that a sufflciently'largenumber of tablets is to be cast to justify the more complex mechanism. As designed and shown the mechanism is particularly suitable for use in an individual drug store in which tablets are to be made up by prescription for the specific use of an individual patient and "are to be cast only in such quantities as may be desired for such purposes. Where large scale use is to be made of the tablets, as for example, in the'mass distribution of vitamin pills, a continuous strip and a mechanical feed mechanism U and in a refrigerator at 4 C. for four hours.

is more desirable. Such machines are well known in the pharmaceutical and candy making fields.

Ecmmple 1 A base was made for a hard gelatin tablet by preparing a carrier mixture consisting of:

Parts Gelatin 50.4

Glycerine 2.8 Pharmaceutical mineral oil (medium grade) 2.8

Water 44.0

The gelatin,- glycerine, mineral oil and water were stirred thoroughly at a temperature of approximately 65 C. until a uniform, homogeneous mixture was obtained. To this mixture was added 5 parts of a pharmaceutical preparation consisting of vitamins A and D as oils and vitamins from the B group as powders. This material was stirred until thoroughly incorporated into the gelatin matrix, and the homogeneous mixture dropped into the mold cavities. The material at this temperature was dropped in such portions that the mold cavity was slightly over filled as shown in Figure 3, whereby the surface tension of the gelatin caused the tablets to assume the symmetrical shape as shown. The material was allowed to dry at room temperature for two hours So produced, the material shrunk slightly and was easily removed from the mold by means of a suction lifting-finger, or other means. The tablets may be additionally conditioned by drying as may be deemed advisable. If desired more water may be added, thus requiring lower temperatures for dropping but longer periods for drying.

Example 2 A tablet was prepared by stirring together:

Parts Gelatin 14.8 Corn 'syr'u'p a 26.6 Medicated oil 26.6 Water 32.0

The water was warmed to 0., the gelatin added, corn syrup added and then the medicated oil. The medicated oil contained such a selection of vitamins, cough inhibitors and other therapeutic agents as was deemed desirable. The material was warmed at 75 to 80 C. and stirred until smooth, then dropped from an ordinary pipette into Teflon molds. The material was allowed to dry at room temperature for several "days until non-sticky to touch and sufficiently rigid to maintain its shape. The exact time depends upon room conditions.

Example 3 A vitamin-containing tablet was prepared containing on an as cast basis:

Parts Vitamin'A 'o'il (55,000 units per gram) 28.9 Vitamin 1) oil "(10,000 units per gram) 0.3 'Corn syrup a 25.0 Gelatin 13.9 Water 31.9

The gelatin was added to water, corn syrup added to the mixture and stirred until smooth at approximately 70 C. The vitamin oils added, mixed, and cast at a controlled temperature of 70 C. into Teflon molds. Ihe material was dried at room temperature until non-sticky.

After approximately 12 hours the material was sufiiciently non-sticky to maintain its shape while being removed from the molds either by hand or by a suction lifter. The tablets maintained their shape after approximately 36 hours drying.

Example 4 A mixture was prepared as above containing:

Parts Vitamin A oil (15,755 units per gram) 20.8 Vitamin D oil (2466. units per gram) 0.7 Tocopherols, 30% 2.0 Vitamin B-1 0.6 Vitamin B-2 0.6 Vitamin C 9.9 Niacinamide 1.5 Calcium pantothenatefl s 3.6 Gelatin 19.? Water 40.6

may be used as solids or dissolved in a mineral oil. Colored tables were cast from the following formulation:

Parts Water (containing certified food coloring) 20.0 Gelatin (acid type) 26.8 Corn syrup 47.9 Glycerine 2.1 Mineral oil (containing vitamins) 3.2

The ingredients, in the order given, were mixed at room temperature, slowly to avoid entrapment of air, then slowly heated to a temperature of 75 C., stirred until homogeneous and clear (about 2 hours) and dropped at a controlled temperature at 55 plus or minus 2 C. At a room temperature of C. the drops of gelatin mixture jelled in about minutes to the point where they Icould be rolled out of the Teflon mold. However, it is considered more desirable to allow them to dry for a longer period so that the material would be shape-stable and not deform when allowed to stand.

Other molded shapes as may be desired may be produced.

Food colors may be introduced into either the oil or water (gelatin) phase of the mix. Similarly water soluble materials may be introduced into the water (glycerine) phase. Perfume or a flavor may be introduced into the aqueous phase if desired.

The tablets cast from harder gelatin base that is, gelatin containing a lower percentage of glycerine and mineral oil as set forth in Example 1 are particularly useful for the administration of vitamins or other pharmaceutical materials which should be released in the stomach or digestive tract at comparatively slow rates. Gelatin tablets prepared in accordance with Example 1 above when tested in synthetic gastric juice at a temperature of 37 0., completely dissolved in an average time of one and one half hours. This slow dissolution and release is frequently beneficial. In the past considerable diiiiculty has been experienced by the sudden release to the stomach of fish oil or other odoriferous materials contained in soft gelatin capsules. This sudden release results in objectionable regurgitation and the Vitamins are released so fast that they may not be properly assimilated. Further, the use of Teflon appears to prevent oil droplets from coming to the interface where they are easily broken. Even when fish liver oils are used, the finished tablets do not possess a fish odor.

By the use of our molds, tablets are produced in the instant machine which permit the slow and uniform release of the desired materials over a prolonged period so that the concentration is low at all times and adequate for :a prolonged period. Such a method of production and such a tablet has never been previously available on a small scale by the individual druggist nor under reasonable economic conditions on a large scale by the pharmaceutical manufacturer because of the difficulty of obtaining a mold material which could be used for a single casting and finishing operation combined.

Whereas a preferred form of the invention has been shown herein it is understood that certain modifications and change in the construction details in the several parts may be made without departing from the spirit of the invention.

We claim:

The method of preparing symmetrical gelatin vitamin tablets which comprises preparing a mixture consisting essentially of gelatin, glycerin, water and vitamins, mixing until homogeneous, droppin a portion of the homogeneous mixture into a polytetrafluoroethylene mold cavity, said cavity having a shape such that, (1) one surface of said portion of the mixture is entirely free from contact with the walls of the cavity, permitting said surface to be shaped by surface tension, said free surface comprising the entire upper portion of said tablet, and (2) that portion of the mixture in contact with the walls of the cavity will have substantially the same configuration as the surface tension gives to the free surface, permitting the mixture to harden, and removing the thus formed symmetrical tablet from the mold.

JOHN C. BIRD. THEODORE G. ROCI-IOW.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,218,591 Taylor Oct. 22, 1940 2,403,476 Berry et a1 July 9, 1946 FOREIGN PATENTS Number Country Date 2,488,446 Switzerland Nov. 15, 949

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