US2996431A - Friable tablet and process for manufacturing same - Google Patents

Friable tablet and process for manufacturing same Download PDF

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US2996431A
US2996431A US398498A US39849853A US2996431A US 2996431 A US2996431 A US 2996431A US 398498 A US398498 A US 398498A US 39849853 A US39849853 A US 39849853A US 2996431 A US2996431 A US 2996431A
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pellets
tablet
matrix
medicinal
thumb
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Barry Richard Henry
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Barry Richard Henry
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2072Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61JCONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/10Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of compressed tablets
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2072Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S252/00Compositions
    • Y10S252/965Retrospective product identification, e.g. tags and tracers

Description

1961 R. H. BARRY 2,996,431

FRIABLE TABLET AND PROCESS FOR MANUFACTURING SAME Filed Dec. 16. 1953 IN V EN TOR.

United States Patent P 2,996,431 FRIABLE TABLET AND PROCESS FOR MANUFACTURING SAME Richard Henry Barry, Bloomfield, NJ. Filed Dec. 16, 1953, Ser. No. 398,498 17 Claims. (Cl. 1tS7-82.)

The present invention relates to pharmaceutical tablets and to a process for manufacturing the same.

It is the general object of the present invention to provide a tablet in which the matrix or binder has embedded therein a number of small pellets so constituted or coated that, at least for the most part, they are not crushed or otherwise integrated with the material of the matrix or binder during the pressing of the tablet, but remain more or less individually distinct from such material and separable therefrom.

A specific object of the invention is to provide a pharmaceutical or medicinal tablet having pellets embedded therein and characterized at the same time both by a high degree of resistance to shock and impact, and thus to chipping or breakage, and by a degree of friability such that it can be crushed and disintegrated into a comminuted state by the pressure of the thumb on the tablet against a table or other surface, preferably aided by a slight turning or twisting movement.

It is a further object of the invention to provide a tablet which is composed essentially of two parts, namely a matrix or binder, and a quantity of small pellets distributed therein and of such size, quantity and hardness that when the pellet is subjected to the pressure of the thumb, accompanied by a slight turning or twisting movement, the pressure being insufficient to crush the pellets, shearing forces are generated which, by reason of the presence of the small pellets, operate to break up even a highly compacted matrix or binder.

Other objects of the invention are to provide a tablet in which the medicinal agent can be contained either in the matrix or in, but preferably on, a relatively large number of pellets distributed therein, or in both the matrix and pellets; to provide a tablet in which there can be incorporated two or more incompatible, i.e. mutually chemically reactive medicinal substances, with the aid of embedded pellets; to provide a tablet wherein the medicinal agent is deposited on a plurality of groups of pellets embedded in the matrix or hinder, the difierent groups of pellets being covered with a protecting or barrier coating of diiferent degrees of thickness, or with coatings of different nature, so that after disintegration of the tablet in the alimentary tract, the pellets belonging to the different groups release their medicinal agent at different times, whereby a protracted or sustained action of the medicinal agent is obtained; and to provide a tablet wherein certain of the aforementioned pellets may be colored or may contain a non-toxic, inert but readily detectable chemical agent to provide tracers whereby the manufacturer may determine whether suspected goods represented as being made by him were actually of his own manufacture.

Other objects and advantages of the invention will appear from the following more detailed description thereof and the features of novelty will be set forth in the subjoined claims.

It is known in the pharmaceutical industry to manufacture tablets of a reduced degree of hardness so that the 2,996,431 Patented Aug. 15, 1961 same can be crushed by the pressure of the finger or thumb to enable such tablets to be taken by mouth by children and also by adults who are unable to swallow a whole tablet. These tablets are consequently of a reduced resistance to shock and impact and are liable to break or chip during transportation, and also during the course of handling during manufacture. For this reason, it is customary to fill the unoccupied space of bottles containing such tablets with a cushioning material, such as a plug of cotton or the like.

It is also known that in the crushing of the just-mentioned type of tablets there is usually obtained a mixture of particles of greatly varying sizes, the larger of which are frequently of such substantial size that they must be subjected to a further crushing action; and because the larger particles are sometimes sharp-edged, there is danger of puncturing the skin of the finger or thumb.

According tothe present invention, there is provided a tablet which can be disintegrated into a mass of small sized particles by the pressure of the thumb (or of the finger) on the tablet and against a table or other surface, in a single operation and without danger of injury to the skin. This high degree of friability is obtained despite the fact that the tablet is shaped under such pressure in manufacture that a tablet which is hard and resistant to shock and impact is produced. The tablet of the present invention is, in fact, friable under thumb pressure even though a tablet composed wholly of the same matrix and formed under the same conditions, including the same degree of pressure, is not friable under the same thumb pressure.

I have found that an otherwise crush-resistant tablet can be made friable under thumb pressure by incorporating therein a certain quantity of small pellets of more or less rounded shapes, such as spheroid, ellipsoid, and ovoid forms, all of these dilferent rounded shapes being hereinafter referred to as spheroid or spheroidal.

The desired effect of the distributed spheroidal particles or pellets is obtained only with a certain minim-um proportion of the weight or volume of such pellets to that of the matrix or hinder; at the same time there is a practical upper limit to the proportion of the spheroidal pellets for the production of an adequately strong and cohesive tablet. It is important also that the spheroidal pellets be of a certain size, in relation to the tablet as a whole, and hence of a certain number, to enable an otherwise crushresistant matrix to be disintegrated to practically a powdered condition by thumb pressure.

I have found that to obtain the results above described, the tablet should be composed of from about 30 to by weight of the spheroidal pellets, the remainder being composed of the matrix or binder. As the densities of the pellets and matrix in the compressed tablet are approximately the same, the weight and volume are about equivalent magnitudes. An easily friable tablet is obtained if the minimum proportion of the spheroidal pellets is about 40% by weight, and in general, best results are obtained when the spheroidal pellets constitute about 50% to 60% of the weight (or volume) of the tablet.

The pellets are of a size ranging from about 10 to 16 mesh, sizes passing through a 12 to 14 mesh screen being preferred, and they may all be of more or less the same size or of dififerent sizes within this range. Thus, by Way of example, a 400 mg. circular tablet of about 9 mm. diameter and of a thickness ranging from about 4 mm. at

the edge to about 6 mm. at the center, can have incorporated therein as many as 100 to 150 spheroidal pellets of about 12 to 14 mesh size.

The spheroidal pellets can be of the type commonly known in the confectionery trade as nonpareil seeds. These are composed of about 65 parts cane sugar, and 35 parts corn starch, plus a quantity of a certified color where they are to be colored. The pellets can, however, be formed of any other inert and harmless material of a comparable degree of hardness, it being noted that the hardness should be such that the pellets, with at most but a relatively few exceptions, are themselves not crushed during the pressing of the tablet, and hence will not be crushed by the disintegration of the tablet with the thumb.

In a further development of the present invention, a tablet composed of a large number of small pellets embedded in a matrix or binder is provided with a medicinal agent coated on the pellets in such a manner that a prolonged or sustained action is obtained. The pellets are provided with a coating of the medicinal agent and such coating is in turn sealed by a protecting or barrier coating whose thickness or character is such that the protecting coatings on different groups of pellets are disintegrated in the alimentary tract at successive time intervals so that a desirable protracted or sustained action of the medicinal is insured. Where the medicinal is to act in the stomach, coatings of different thicknesses are applied to diflerent groups of pellets so that the stomach fluids disintegrate such coatings at successive periods during the time that the pellets remain in the stomach; or such different groups of pellets may be given different coatings which dissolve in the stomach at different rates. Where the medicinal agent is to act in the intestinal tract, different groups of pellets are provided with outer protective or barrier coatings, commonly called enteric coatings, and with an timer or intermediate coating or coatings, so that the medicinal coating on the different groups of pellets becomes exposed at different time intervals. As already indicated, the coatings can be of the same material but of different thicknesses; or they may be of approximately the same tln'ckness but of different materials which dissolve at different rates in the intestinal fluids. These coatings are known in the art and may, for example, consist of shellac, synthetic resins, such as vinyl and urea resins, cellulose esters, like the acetate, and acetate-phthalate, and the like. While the medicinal agent is preferably coated on the pellets, it can, of course, also be incorporated within the pellets, or in only certain groups of pellets, so that the matrix of the pellets will further delay the action of the medicinal in such pellets. Coatings of different thicknesses can be provided either by employing solutions of the coating material of different concentrations, or by applying different numbers of coatings of the same solution on the different groups of pellets. Part of the medicinal agent can also be contained in the matrix and such medicinal portion will be brought into action first. Thus the matrix or binder can contain barbiturates, analgesics, sulfa drugs, antihistamines, and the like, and where the medicinal agent is itself not capable of being pressed into a coherent tablet, or the quantity thereof is too small, it may be mixed with excipients such as sugar, starch, or other known components of tablet mixes capable of being reduced to a granular or substantially powdery condition; and, as will be understood, the mix will be composed of such known tablet excipients also when it contains no medicinal agent. Where the medicinal agent is to act only in the intestinal tract, the Whole tablet can be provided with an enteric coating, but I prefer to coat the pellets themselves in this way because, as above indicated, the tablet may be crushed prior to ingestion.

The preparation of a tablet composed of pellets embedded in a matrix makes it possible also to incorporate in a tablet two or more incompatible substances, that is, substances which are mutually reactive, such as citric acid and sodium bicarbonate in the case of an effervescent '4 tablet. Thus one of the reactive agents can be incorporated in the matrix or binder and the other within or on the pellets which are then coated with sugar or with a barrier or delaying coating, such as shellac, synthetic resin, cellulose acetate, acetate-phthalate, and the like. The incompatible medicinal agents can also be incorporated within or coated on diflerent groups of pellets and then encased within a protecting coating which is disintegrated in the stomach or in the intestines. Examples of incompatible but simultaneously administered medicinal agents are aminophylline or other basic medicinal agent and an acid salt, such as ephedrine sulfate, antihistaminic salts such as Chlor-trimeton (l-parachlorophenyl l (2 pyridyl) 3-dimethylaminopropane maleate), and the like; calcium ereosotate and alkaloid salts like codeine phosphate; vitamin B and reducing agents like ascorbic acid or ferrous salts.

The pellets can also be employed to support coatings or films of a medicinal having a bitter or other disagreeable taste, in which case the medicinal coating can be covered with a coating of sugar which may be flavored, if desired. If the pellets are to be covered with an enteric or other barrier coating, then the sugar coating can in such case be dispensed with.

The pellets can all be of more or less the same color as the matrix, which is usually white. However, one or a few of the pellets in each tablet can be colored to serve as a tracer to enable a manufacturer to ascertain whether suspected tablets sold as products of his manufacture were actually made by him. The number of such colored pellets in the mixture which is to be pressed into tablets should be of suflicient quantity to insure that at least one such colored pellet will be contained in nearly all of the tablets. If desired, a large number of the pellets, or even all of them, can be colored and preferably different groups of pellets can be given difierent colors to make the tablet more attractive to children who might otherwise refuse to take the medicine.

The accompanying drawing shows by way of example a table prepared in accordance with the invention; in said drawing:

FIG. 1 is a central section through the tablet; while FIG. 2 is an enlarged central section through a pellet provided with a medicinal and a protecting coating.

Referring to the drawing, the tablet is shown at 10 and is composed of a binder or matrix 11 and of a large number of pellets 12 of spheroidal shape. The pellets are indicated to be more or less true spheres, but it will be understood that, as mentioned above, they need not be of any regular shape but may have a non-circular, although preferably entirely rounded, outline.

As will be evident from FIG. 1, the presence of the pellets destroys the continuity of the matrix, and where the pellets are of sutficient number, as proposed by the present invention, the mass of material between the pellets is quite thin. Consequently, upon pressure of the thumb upon a tablet resting on a non-yielding surface, and especially if the thumb is given a slight turn as the pressure is applied, the hard pellets are caused to exert shearing and crushing forces along numerous areas and planes within the matrix which, because of the thinness of the intervening material, operate to break up the matrix and reduce it practically completely to its originally powdery or granulated condition. The pellets, however, being quite hard, will not themselves be crushed by the thumb pressure. This disintegrating action occurs despite the fact that the matrix is quite hard and strong, so much so that. a tablet composed entirely of the matrix material and made under the same conditions would not be crushable with the thumb.

FIG. 2 shows a pellet 12 provided with a core 13 which may be a nonpareil seed, as above described. This core may or may not contain a medicinal agent, while the pellet as a whole is provided with a coating 14 of a medicinal agent. About the coating 14 is a protecting or barrier film 15 which is made of one of the coating materials above described or a material having an equivalent action or function.

In manufacturing the tablet, the nonpareil seeds in adequate quantity are mixed as uniformly as possible with the matrix material, which may or may not contain a medicinal agent, such matrix material :being in the granulated or powdery condition. The tablets are then shaped under a pressure of about 1 /2 to 2 tons per square inch. This pressure operates to compress the matrix into a solid, hard mass which even at the sharp edges of the tablet is resistant to chipping and breakage both during the handling of the tablets in the course of manufacture and packaging, and during transportation when the tablets may strike against each other and against the wall of the bottle or other container.

To make the tablets attractive to children, the nonpareil seeds or pellets, or the coatings thereon, can be given a variety of colors, and these may contrast with a colored matrix, so that when the tablet is crushed, a more or less powdery colored matrix mass is obtained which is mixed with the relatively large and variously colored pellets. For tracer purposes, as above stated, only a very small proportion of the pellets need be colored.

As above described, either the pellets alone, or the matrix alone, or both may serve as carrier for a medicinal agent; and different and even mutually incompatible medicinal agents can be carried by the pellets and matrix, or by different groups of pellets. Thus in one satisfactory form of tablet the matrix of each tablet contains a mixture of about 3.5 gr. of acetylsalicyclic acid (aspirin), 2.5 gr. of acetophenetidin (phenacetin) and 2.0 mg. of 1- parachlorophenyl 1 (2 pyridyl) 3 dimethylaminopropane maleate (Chlor-Trimeton).

While it is generally desirable to provide a protective coat on the pellets when different groups thereof are coated with incompatible medicinals, such protective coat can in certain cases be dispensed with, -by first agitating the different groups of medicinally coated pellets with a portion of the powdered matrix to provide a protective film of the matrix about the pellets, then mixing the socoated pellets and pressing the mix.

As examples of readily assayable or detectable ingredients of tracer pellets may be mentioned bismuth compounds like the sub-nitrate, and quinine sulfate and other substances which fluoresce under ultra-violet light.

I claim:

1. A pressed medicinal tablet which is resistant to breakage and chipping under impact but is capable of being crushed and disintegrated by the pressure of the thumb, said tablet being composed of about 30 to 70% by weight of hard, spheroidal medicinal pellets of about to 16 mesh, distributed in about 70 to 30% by weight of a comminuted matrix which is compacted into a hard, strongly cohesive mass which, in the form of a tablet composed wholly thereof, is highly resistant to being crushed with the thumb, said tablet on application of thumb pressure with a twisting motion being readily disintegrable, by reason of shearing forces transmitted by said pellets, into a substantially powdered matrix containing the spheroidal pellets in substantially undamaged condition.

2. A tablet as defined in claim 1, wherein the pellets constitute about 50 to 60% by weight of the tablet and are of about 12 to 14 mesh.

3. A tablet as defined in claim 1, wherein the matrix is composed at least in part of a medicinal agent.

4. A tablet as defined in claim 1, wherein at least some of the pellets have thereon a coating of a medicinal agent.

5. A tablet as defined in claim 1, wherein at least some of the pellets have thereon a coating of a medicinal agent, there being a protective coating over such medicinal coating.

6. A tablet as defined in claim 1, wherein difierent groups of pellets are provided with a protective coating of diflferent thicknesses to cause the medicinal agent of such groups of pellets to be brought into action at different times.

7. A tablet as defined in claim 1, wherein the medicinal agent is present as a coating on the pellets, different groups of such medicinally coated pellets being provided with a protective coating having different rates of disintegration in the alimentary tract, whereby the medicinal agent of such different groups of pellets is brought into action at different times in the ailrnentary tract.v

8. A tablet as defined in claim 1, wherein at least some of the pellets have a color difierent from that of the matrix.

9. A tablet as defined in claim 1, wherein difierent groups of pellets have different colors, such colors being different from that of the matrix.

10. A tablet as defined in claim 1, wherein different groups of pellets are provided with mutually incompatible medicinal agents.

'11. A tablet as defined in claim 1, wherein the matrix contains a mixture of aspirin, phenacetin and an antihistaminic.

12. A tablet as defined in claim 1, wherein at least some of the pellets have thereon a coating of a medicinal agent, there being a protective coating over such medicinal coating, the protective coatings of different groups of the medicinally coated pellets having dilferent degrees of resistance to the fluids of the alimentary tract, whereby the groups of pellets are disintegrated progressively, and the medicinal agents of the different groups of pellets are brought into action at different times within the alimentary tract.

13. A pressed medicinal tablet comprising a pressuremolded matrix having embedded therein a quantity of discrete, hard, uncrushed, spheroidal pellets constituting from about 30% to 70% by weight of the tablets, at least certain of said pellets carrying a medicinal agent, said matrix being disintegrable by pressure of the order of that applicable by the thumb to release said pellets in substantially undamaged condition.

14. A pressed medicinal tablet comprising a pressuremolded matrix having embedded therein a quantity of discrete, hard, uncrushed, spheroidal pellets constituting from about 30% to 70% by weight of the tablet, said pellets being composed of a plurality of groups carrying a medicinal agent, the pellets of said groups having thereon inert protective coatings which differ in the plurality of groups in their rates of disintegration in the alimentary tract, whereby a prolonged medicinal action is obtained, said tablet being disintegrable by pressure of the order of that applicable by the thumb without crushing of the pellets.

15. A pressed medicinal tablet comprising a pressuremolded matrix having embedded therein a quantity of discrete, hard, uncrushed, spheroidal pellets of 10 to 16 mesh constituting from about 30% to 70% by weight of the tablet, said matrix being disintegrable to release said pellets in substantially undamaged condition, and said pellets being provided with a medicinal agent, difierent groups of such pellets having thereon inert coatings characterized by different rates of disintegration in the alimentary tract whereby a sustained medicinal action is obtained, said tablet being disintegrable by pressure of the order of that applicable by the thumb Without crushing of the pellets.

16. A pressed medicinal tablet for oral administration having a compressed matrix of such hardness and strength that a tablet composed thereof is normally highly resistant to being crushed by the thumb, said matrix having embedded and distributed therein a quantity of discrete, hard, uncrushed spheroidal pellets carrying a medicinal agent and constituting from about 30% to about 70% by weight of the tablet, said tablet on application of thumb pressure 8 with a tfwilslting mgtion being reading disigtegrl'fble, by FOREIGN PATENTS reasono s earingorces transmitte y sai pe ets into a substantially powdered matrix containing the spher oidal 109438 Austmha 9 pellets in substantially undamaged condition. OTHER REFERENCES 17. A tablet as defined in claim 15, wherein mutually 5 Modern Drug Encyclopedia edition Drug Publi. incompatible medicinal agents are provided on different ations, Inc New York, 1955, p. 72, A-P-Cillin. groups of pellet Gutman: Modern Drug Encyclopedia," 5th edition,

References Cited in the file of this patent Pubhcations, Inc., New York, February 1952, page UNITED STATES PATENTS 10 Silver et -al.: Manufacture of Compressed Tablets, 2,738,303 Blythe Mar. 13, 1956 F. J. Stokes Machine Co., 1944, pages 10 and 11.

ULITED STATES PATENT OFFICE CERTIFICATION OF CORRECTION Patent No. $996,431 Y I August 15 1961 Richard Henry Barry It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

In the grant lines 1 2 and 3, for "Richard Henry Barry, of Bloomfield New Jersey read Richard Henry Barry, of Bloomfield, New Jersey, assignor to Schering Corporation of Bloomfield New Jersey a corporation of New Jersey line 12, for "Richard Henry Barry his heirs" read Schering Corporation its successors in the heading to the printed specification lin'gx 4 for Richard Henry Barry Bloomfield N. J." read Ric ard Henry Barry, Bloomfield N, J. v assignor to Schering Corporation Bloomfield N. J a corporation of New Jersey Signed and sealed this 21st day of November 1961,

(SEAL) Attest:

ERNEST W. SWIDER DAVID L. LADD Attesting Officer Commissioner of Patents UMTED STATES PATENT OFFICE CERTIFICATION OF CORRECTION Patent No. 2 '996,43l August 15 1961 Richard Henry Barry It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

In the grant, lines 1 2 and 3, for "Richard Henry Barry of Bloomfield New Jersey read Richard Henry Barry, of Bloomfield, New Jersey, assigno r to Schering Corporation of Bloomfield New Jersey a corporation of New Jersey *5 line 12, for "Richard Henry Barry his heirs" read Schering Corporatiom its successors in the heading to the printed specification line: 4,, for Richard Henry Barry, Bloomfield N. J read Richard Henry Barry, Bloomfield N. J. assignor to Schering Corpora'tiom Bloomfield, N. J a corporation of New Jersey Signed and sealed this 21st day of November 1961,,

(SEAL) Attest:

ERNEST w. SWIDER DAVID LADD Attesting Officer Commissioner of Patents

Claims (1)

1. A PRESSED MEDICINAL TABLET WHICH IS RESISTANT TO BREAKAGE AND CHIPPING UNDER IMPACT BUT IS CAPABLE OF BEING CRUSHED AND DISINTEGRATED BY THE PRESSURE OF THE THUMB, SAID TABLET BEING COMPOSED OF ABOUT 30 TO 70% BY WEIGHT OF HARD, SPHEROIDAL MEDICINAL PELLETS OF ABOUT 10 TO 16 MESH, DISTRIBUTED IN ABOUT 70 TO 30% BY WEIGHT OF A COMMINUTED MATRIX WHICH IS COMPACTED INTO A HARD, STRONGLY COHESIVE MASS WHICH, IN THE FORM OF A TABLET COMPOSED WHOLLY THEREOF, IS HIGHLY RESISTANT TO BEING CRUSHED WITH THE THUMB, SAID TABLET ON APPLICATION OF THUMB PRESSURE WITH A TWISTING MOTION BEING READILY DISINTEGRABLE, BY REASON OF SHEARING FORCES TRANSMITTED BY SAID PELLETS, INTO A SUBSTANTIALLY POWDERED MATRIX CONTAINING THE SPHEROIDAL PELLETS IN SUBSTANTIALLY UNDAMAGED CONDITION.
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US3125490A (en) * 1964-03-17 Tablet with contrasting indicia and method
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US4642233A (en) * 1982-03-22 1987-02-10 Alza Corporation Gastrointestinal drug delivery system comprising a hydrogel reservoir containing a plurality of tiny pills
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