US3336200A - Tablet structure - Google Patents

Description

g-v 96 G. KRAUSEY ETAL 3,336,200

TABLET S TRUCTURE Filed Ocit. 1, 1963 INVENTORS:

FRED C. NINGER GEORGE M. KRAUSE ATTORN EY United States Patent This application is a continuation-in-part of application Ser. No. 150,000, filed Nov. 3, 1961, and now abandoned.

The present invention relates to a method for the preparation of a novel tablet structure and relates more particularly to a method for the preparation of a unitary pharmaceutical tablet structure formed of a plurality of separable sections normally joined to each other in such manner that the sections may readily be separated from each other by the application of a moderate manual pressure.

An object of this invention is the provision of a unitary pharmaceutical tablet normally constituting a single dosage unit but formed of sections which may be accurately divided and conveniently separated into individual dosage units.

Another object of this invention is to provide a method for the preparation of a readily divisible compressed tablet of novel configuration and composition which has a low bulking factor and which is adapted to nest readily in a container on random fill.

A further object of this invention is to provide a method for the preparation of a unitary compressed tablet structure which is suitably sectioned and which is adapted to be further processed by film coating or other tablet surface coating without impairing the ease and reliability with which said sectioned tablet structure may be subdivided into plurality of dosage units.

Other objects will appear from the following detailed description of the present invention.

Compressed tablets are widely employed'as a means of marketing many products in the drug industry where individual dosage units are desired. To form tablets, a suitable, freely-flowing granulation is prepared and fed to a tablet press. The press may operate with a single set of punches, or a high speed rotary tablet press may be employed where a large series of punches operate on a high speed rotary bed. The shape of the surfaces of the punches or dyes between which the granulation is compressed determines the shape of the tablet which is formed and an infinite variety of shapes and monogrammed surfaces may be obtained. Aside from variations in the peripheral shape of such compressed tablets, these tablets, most commonly, are either flat-faced or have slightly convex surfaces. For ease of subdivision, may tablets are centrally scored across one surface. An example of such a tablet is that disclosed in the Wilhelm patent, US. Pat. No. 2,386,416. In the case of small and moderately thick tablets formed of granulations containing appreciable quantities of waxy or wax-like diluents, scoring 1 proves of little advantage since such diluents tend to produce strong and hard tablets which are rather brittle. Such tablets are not very amenable to subdivision by ordinary manual pressure, and usually are difficult to break for purposes of obtaining a predetermined fractional dosage. Hence, where several different dosage schedules may be recommended to a patient, the difiiculty of subdividing these tablets to follow such schedules may require the production of several different tablet sizes rather than the production of one size which can be conveniently and accurately subdivided into fractional dosage units. Where the original compressed tablets require a film or othersuitable coating in order to produce a technically satisfactory as well as a pharmaceutically acceptable product, such coatingstend to obliterate any 3,336,200 Patented Aug. 15, 1967 scoring to such a degree that the subdivision of a large coated tablet into subdivided dosage forms is quite impractical and unsatisfactory.

In accordance with the present invention, there is now provided a method for the preparation of an improved pharmaceutical tablet of a new and novel structure, which can be readily formed by compression, as described, in either a coated or an uncoated form and which may easily be subdivided into a plurality of dosage units by the simple application of a moderate manual pressure. The present invention is more clearly illustrated by the accompanying drawing in which there is shown several modifications of the improved tablet structure of this invention.

In the drawing:

FIG. 1 is a view in perspective of a tablet structure of this invention having one of the two faces formed of angularly disposed surfaces with the other face being a fiat surface lying in a single plane, and

FIG. 2 is a view in perspective of a tablet structure of this invention in which each of the two faces comprises a plurality of surfaces angularly disposed with respect to each other, and

FIG. 3 is a further modification of the tablet structure of this invention wherein the tablet may be subdivided into more than two sections.

Like numerals indicate like parts in the several views of the drawing. 1

Referring now to the drawing, and more particularly to FIG. 1, the tablet structure shown comprises a lower face 5 and an upper face 6 divided into sections 7 and 8. As shown each of sections 7 and 8 lie in separate planes .which intersect along a line 9 and form an angle A in tercepting an arc of less than 180 and preferably an arc of about to about The material forming the tablet structure is thicker at the sides than it is at the center and the thinnest portion lies along the line 9 where the surfaces of sections 7 and 8 intersect. Line 9 may be defined merely by the intersection of the surfaces of sections 7 and 8 or it may be defined by providing a somewhat deeper score line, as shown. In order to subdivide the unitary tablet structure and to separate it into individual dosage units a moderate manual pressure is applied to the upper and lower faces of the tablet by means of the thumb and forefinger. The leverage exerted on the separate sections of the upper face has its fulcrum along line 9 and since the thinest portion of the tablet lies along line 9 it is easily broken there thus forming two equal halves.

While the tablet structure shown in FIG. 1 is of unequal thickness from the edges to the center, the tablet may also be of uniform thickness as shown in FIG. 2. In this modification both the upper face 10 and the lower face 11 are formed of separate sections, the upper face 11 consisting of sections 12 and 13 lying in separate planes which intersect along a line 14. The lower surface 11 is similarly formed of separate sections the surfaces of which lie parallel to the surfaces 12 and 13, respectively, and which meet along a line 15 on the lower face of the tablet structure. Line 14 may comprise a somewhat deeper score line, if desired. The tablet structure shown in FIG. 2 is readily subdivided into separate dosage units merely by placing the tablet between the thumb and forefinger and by applying manual pressure. The leverage exerted by pressure upon the sections of the upper face cause the tablet to split readily along line 14 and to yield equal halves forming separate dosage units.

The tablet structure shown in FIG. 3 enables a single dosage unit to be subdivided to form either two or four separate dosage units. In this structure the upper face of the tablet 16 is divided into separate sections 17, 18, 19 and 20, respectively, with the surfaces of sections 17 and 20 lying in one plane and the surfaces of sections 18 and 19 lying in another plane, each of said planes being at an angle to each other embracing an arc of less than 180 and meeting in a line 21. In this respect tablet 16 is similar to that shown in FIG. 1 and may similarly be subdivided into two separate units along line 21 by the application of manual pressure. However, in order to enable tablet 16 to be further subdivided additional scoring is provided to separate the surface of section 17 from the surface of section 20 and similarly, the surface of section 18 from the surface of section 19 thus forming spaces 22 and 23 which may be joined at the base of the tablet (not shown) or merely be open.

The novel tablet structures of this invention are especially valuable for use where the tablets contain therapeutic agents together with a substantial amount of a wax or similar diluent in order to obtain a timed and sustained release of the active ingredient since a substantial proportion of waxes in the tablet composition tends to form a very hard and brittle tablet which is diflicult to subdivide when formed into the usual shapes. For example, when an ordinary flat-faced sugar tablet is formed by compression of 400 milligrams of sugar to a thickness of 0.160" and a diameter of with a score line on the top and bottom surfaces, such a tablet will easily fracture since it will have an average hardness of less than about 6 to about Strong-Cobb units as measured on a tablet hardness testing machine customarily used for determining the hardness or resistance to crushing of pharmaceutical tablets. An example of such a testing machine which has been widely adopted in the art is described in Albrecht U.S. Patent No. 2,645,936. In contrast, a tablet of similar size and construction formed of a composition having a substantial quantity of waxy fillers or diluents therein may have an average hardness of about to about 25 Strong-Cobb units, which makes it extremely difficult, if not impossible, to fracture with manual pressure exerted solely by ones fingertips. A waxy filled tablet formed by the present structure, however, may be readily fractured into equal dosage units by a moderate finger pressure. Although the present structure may be employed in construction of relatively soft tablets such as those having a Strong-Cobb hardness of less than about 10, it finds its greatest utility in application to those tablets having a Strong-Cobb hardness of greater than about 12 to about 15, which tablets may not be easily fractured into separate dosage units when in the shape of conventional tablets.

In order further to illustrate this invention, the following examples are given:

EXAMPLE 1 A granulation is prepared of the following components. Ingredient: Parts by wt. Carnauba wax 4 Stearic acid l6 Phenylpropanolamine hydrochloride 10 Lactose 50 Color 0.03

The carnauba wax is melted at 85 C. and the stearic acid is then added to the molten solution. The phenylpropanolamine hydrochloride and lactose are then added to the molten mixture obtained after which a solution of the color in a small amount of water is also added. The mass is mixed until uniform and allowed to solidify in trays. After solidification, the mix is granulated by being passed through a mill.

A second granulation is prepared from the following components.

Ingredient: Parts by wt. Polyethylene glycol 4000, USP 4 Lactose Phenylpropanolamine hydrochloride 5 Color 0.005 Magnesium stearate 0.2

The polyethylene glycol is heated to 70 in a suitable mixer. The lactose and the phenylpropanolamine hydrochloride are then slowly added to the polyethylene glycol. The color is next dissolved in 1.66 parts by weight of water and added as a solution, with mixing, to the other ingredients. After a substantially uniform blend is obtained, the mixture is transferred to trays where it is allowed to solidify. The solidified material is then milled to form a granulation with which the magnesium stearate is uniformly blended.

The separate granulations are then compressed into double layer tablets whose layers are of substantially uniform thickness, each tablet weighing about 705 milligrams, the bottom layer (first granulation) weighing up to about 485 milligrams. The punches employed are shaped to produce a center scored tablet in which the two halves of the tablet which meet along the score line are at an angle of 135 to each other. The tablets obtained even though the bottom layer is of a hard, waxy structure may easily be divided into two halves by exerting manual pressure on the tablet with the forefinger so as to divide it into separate dosage units. The tablets are found to have an average hardness of about 18 Strong-Cobb units.

EXAMPLE 2 A sustained release and an immediate release granulation are each prepared in the following manner:

Sustained aclion' granulation Eight parts by weight of carnauba wax are heated at C. in an agitator and 32 parts by weight of stearic acid are added and mixed until a uniform melt is obtained. To this melt is then added 50 parts by weight of phenyltoloxamine dihydrogen citrate and 70 parts by weight of lactose. After the melt has been uniformly mixed, 6.5 parts by weight of phenobarbital are added followed by a solution of 0.033 part by weight of FD & C Yellow No. 5 in 0.8 part by weight of water. The waxy mixture is then spread in thin layers on drying trays and broken up into small particles after hardening. The mixture is then milled to granular form and blended with 1.3 parts by weight of magnesium stearate.

Immediate release granulation 7.33 parts by weight of polyethylene glycol 4000 are heated to 70 C. 60 parts by weight of lactose, 3.33 parts by weight of phenobarbital and 10 parts by weight of phenyltoloxamine dihydrogen citrate are then gradually added to the heated polyethylene glycol. To this mixture is added, 0.003 part by weight of PD & C Yellow No. 5 in 3.33 parts by weight of water. The uniform mixture obtained is then placed on drying trays and after solidification the mixture is milled to a granular form. 0.3 part by weight of magnesium stearate is then thoroughly blended with this granulation. The immediate release granulation and the sustained release granulation are then compressed into V-shaped double layer tablets weighing about 753 milligrams, with the sustained action layer weighing about 524 milligrams. The tablets are formed to a general V-shape tablet between suitably shaped punches yielding tablets of uniform thickness whose sides meet at an angle of about In this composition the sustained release layer constitutes a hard, waxy formulation, yet the tablet may easily be subdivided into two equal parts by pressure of the forefinger. The tablets so formed are found to have an average hardness of about 16 Strong- Cobb units.

EXAMPLE 3 The following separate granulations are prepared in the manner described above.

Ingredient: Parts by wt. Phenylpropanolamine hydrochloride 2.5 Ephedrine hydrochloride 7.5 Sodium butabarbital 12 Starch Lactose 20 Stearic acid powder 3.5 Polyethylene glycol 6000 3 Phenylpropanolamine hydrochloride 37 Stearic acid powder 24 Ethyl cellulose .5 Carnauba wax 2.5 Sugar 26 FD & C Red No. 4 0.08 FD & C Red No. 2 0.1 Water 1 Ephedrine hydrochloride 65 Stearic acid powder 17 Camanba wax 14 Ethyl cellulose 4 Magnesium stearate 1 PD & C Red No. 4 0.03 Water 1.7

Granulations B and C are mixed and this mixture is then compressed with granulation A into double layer tablets weighing about 450 milligrams, the top layer being granulation A with the bottom layer weighing about 240 milligrams. The overall tablet thickness is about 0.23 inch and the tablet so formed is generally of the V-shape tablet wherein the thick sides meet at the center at an angle of about 135. The lower or sustained release waxy layer, although quite hard, is readily divisible together with the upper immediate release layer by merely exerting pressure on the tablet by the forefinger. The tablet is found to have an average hardness of about 15 Strong-Cobb units.

It is understood that the foregoing detailed description is given merely by way of illustration and that many variations may be made therein without departing from the spirit of our invention.

What is claimed is:

A compressed V-shaped center scored double layer tablet, having a drug in two separate granulations, comprising:

(a) an immediate release drug granulation of a drug in tablet granulation excipients and lubricant in the upper layer, and

(b) a sustained release drug granulation of the same drug in carnauba wax and stearic acid with tablet granulation excipients in the lower layer, said separate immediate and sustained release drug granulations, of the same drug, having been compressed into V-shaped center scored double layer tablets having an average hardness of about 15-18 Strong-Cobb units and layers of substantially uniform thickness, wherein the two top halves constituting the upper plane surfaces of the tablets are joined at the center score at an angle of about to each other so that the application of a unidirectional finger pressure exerted on the center of the lower face of the tablet placed with the upper face down on a firm surface causes the tablet to split into two equal halves, each half containing predetermined fractional dosages of the same drug in both an immediate release drug granulation and in a sustained release drug granulation.

References Cited UNITED STATES PATENTS D 91,644 3/1934 Blackstone 163 2,082,312 6/1937 Todd 99-138 2,082,313 6/1937 Todd 99l38 2,798,443 7/1957 Martell l071 2,809,917 10/1957 Hermelin 167-82 2,887,438 5/1959 Cooper et al. 16782 2,951,792 9/1960 Swintosky 16782 3,048,526 8/1962 Boswell 167--82 3,145,146 8/1964 Lieberman et al. 167-82 D 201,497 6/ 1965 Ninger 16-3 D 202,467 10/1965 Guilmot 16--3 FOREIGN PATENTS 352,208 9/1937 Italy. 808,014 1/1959 Great Britain.

OTHER REFERENCES Atlas Pharmaceutical Bulletin, A Guide to Using Atlas Mannitol, N.F., as a Base in Press-Coated and Multi- Layer Tablets, 12 pp. August 1959.

Tsevdos: Press-Coated and Multi-Layer Tablets, Drug & Cosmetic Industry 78 (1), pp. 38-40, 113-114, January 1956.

LEWIS GO'ITS, Primary Examiner.

S. K. ROSE, Assistant Examiner.

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