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US3927194A - Tablet formulation - Google Patents

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US3927194A
US3927194A US52942374A US3927194A US 3927194 A US3927194 A US 3927194A US 52942374 A US52942374 A US 52942374A US 3927194 A US3927194 A US 3927194A
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tablet
mg
weight
tablets
formula
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Ehud Geller
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IVES LAB Inc
IVES LABORATORIES Inc
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IVES LAB Inc
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    • 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

Abstract

The disclosure is directed to formulations for tablets which are to be deeply grooved to facilitate breaking into predetermined portions by the user. A critical tablet weight for deeply grooved tablets is disclosed.

Description

[ 51 Dec. 16, 1975 Geller TABLET FORMULATION [75] Inventor: Ehud Geller, King of Prussia, Pa.

[73] Assignee: Ives Laboratories Inc., New York,

[22] Filed: Dec. 4, 1974 [21] Appl. No.: 529,423

Related US. Application Data [62] Division of Ser. No. 312,469, Dec. 6, 1972, Pat. No,

[52] US. Cl 424/15; 424/362 [51] Int. Cl. A61J 3/10; A61K 9/00 [58] Field of Search 424/15, 362

[56] References Cited UNITED STATES PATENTS 1,836,604 12/1931 Meyer 127/30 3,146,168 8/1964 Battista 424/362 3,336,200 8/1967 Krauss et a1. 424/19 3,723,614 3/1973 Langaver 424/15 D91,644 3/1934 Blackstone.. D1 D201,497 6/1965 Ninger DIG3 D202,467 10/1965 Guilmot DIG3 FOREIGN PATENTS OR APPLICATIONS 1,200,790 9/1965 Germany 352,208 9/1937 Italy 6,614,611 4/1967 Netherlands OTHER PUBLICATIONS Reier et al., J. Pharm. Sci. 55(5), 510-514 (1966) Microcrystalline Cellulose in Tabletting.

Reier Diss. Abst. 25(5) 2933 (1964), Microcrystalline Cellulose in Tabletting.

Fox et al., Cosmetic Ind. 92:161-164, 258-261 (1963), Microcrystalline Cellulose in Tabletting. Battista et al., Ind. Eng. Chem. 54(9): 2029 (1962), Microcrystalline Cellulose.

Woods, Am. Perfumer Cosmet. 80(4): 51-53, 5560 (1965), Microcrystalline Cellulose, A New Ingredient for Pharmaceuticals and Cosmetics.

Atlas, Chem. Ind. Inc., 1969, 16 pp. Atlas Mannitol NE. A Definitive Guide to Its Properties and Use as a Tablet Excipient.

Atlas, Chem. Ind. Inc., 1973, 16 pp. Atlas Mannitol USP Tablet Excipient.

Primary Examiner-Shep K. Rose Attorney, Agent, or Firm-Joseph Martin Weigman [57] ABSTRACT The disclosure is directed to formulations for tablets which are to be deeply grooved to facilitate breaking into predetermined portions by the user. A critical tablet weight for deeply grooved tablets is disclosed.

9 Claims, 6 Drawing Figures US. Patent Dec. 16, 1975 FIG.2

FIG

FIG

FIG

TABLET FORMULATION This application is a division of application Ser. No. 312,469 filed Dec. 6, 1972, now US. Pat. No. 3,883,647 dated May 13, 1975.

This invention relates to novel formulations for tablets which are to be deeply grooved. Deeply grooved tablets are those in which the groove is /3 to /a of the total tablet thickness. Such tablets are shown for instance in US Pat. No. 224,591 and in copending application Ser. No. 388,142 filed Aug. 6, 1973. The tablet design allows for easy, simple and accurate division of a pharmaceutical tablet.

In the manufacture of tablets a groove, or bisect. or score, may be formed on one of the tablet faces. The groove facilitates breaking of the tablet into two parts by applying pre'sssure while the tablet is held between two fingers or in both hands.

In the pharmaceutical industry dividing a tablet into two or more accurate predetermined parts permits the administration of two or more doses of the active ingredient, or drug, contained in the tablet. Potent drugs are frequently incorporated in small amounts into a total tablet formulation, and the capability to divide the tablet accurately allows for a saving by not having to formulate, package and distribute different sized tablets for a portion of the dose and for the full dose. In addition, it is often beneficial to the chemical stability of the drug to incorporate the full dose in the smallest tablet size available. The inclusion of one-half of that dose in a tablet of similar size decreases the relation of drug to excipients twofold. thus in many cases also increasing the possibility of drug degradation due to drug-excipient interaction.

Some of the problems that arise in the production of regularly grooved tablets are:

1. Depending on its hardness, it is sometimes impossible to break the tablet although it is scored.

2. Scores do not always assure precise division of the tablet.

3. Pharmaceutical tablets of smaller sizes do not allow for ease of holding and breaking; in which case the patient very often resorts to using other means of dividing the tablet which results in losing parts of it or obtaining uneven parts or both.

Typical deeply scored tablets to which the present invention is applicable are shown in the drawings in which:

FIG. 1 is an isometric view of a pharmaceutical tablet employing a deeply scored design:

FIG. 2 is a top plan view thereof:

FIG. 3 is a side elevational view thereof as seen at right angles to FIG. 2;

FIG. 4 is an end elevational view thereof as seen at right angles to FIG. 2;

FIG. 5 is an end elevational view of a pharmaceutical tablet embodying a modification to the form illustrated in FIG. 4; and

FIG. 6 is a bottom view of the embodiments of FIGS. 1 and 5.

The deeply grooved tablet design presents tablet compression characteristics which are not typical of the manufacturing of conventional pharmaceutical tablets. While tablets are usually compacted between uniform surfaces. flat or concave, the deeply grooved tablet design presents a non-uniform compressing surface on one tablet face and a uniform face. spherical or flat. on the other. Such a multiplanar surface presents a process of physical compaction which does not produce the results expected from a conventional compressed tablet. In the process of compaction. the multiplanar surface applies forces, the resultant of which is not vertical. This results in nonuniform stress distribution within the tablet as an independent unit which in turn causes tablet capping and the inadequate imprinting or embossing of indicia of any of its surfaces. In addition, the uneven distribution of stresses results in varying levels of lubrication effectiveness of the tablet planes in contact with the press tooling which. in turn. causes picking" of material off the tablet surface. To overcome this phenomenon requires a highly cohesive mixture which is at the same time sufficiently lubricated to enable friction-free tooling to tablet contact on all tablet planes. In practice the tablet formulator has to balance the lubricant level against the binder level because the increase of the former will diminish the effect of the latter until the critical region of such action is surpassed.

Picking and sticking are words of art, meaning part of the tablet sticks to the tips of the upper or lower punch. Capping describes a condition in which the tablet laminates into one or more layers.

This invention has been directed principally to the application of specific pharmaceutical formulations incorporating isosorbide dinitrate as the active ingredient. but is applicable to other deeply grooved tablets as well. Isosorbide dinitrate is a potent coronary vasodilator.

It was originally presumed that existing, acceptable. direct compression, tableting compositions could be adequately compressed with deep scoring tooling. Two such compositions were evaluated and surprisingly. it was found that acceptable tablets could not be made. Using a placebo composition (one without an active ingredient) similar to a presently used acceptable isosorbide dinitrate tablet composition, it was determined that, unexpectedly, a total tablet weight was critical to obtain acceptable tablets. To minimize the problems caused by stress non-uniformity, an optimal weight was found where after sufficient compression the distance between the apex of the convex side of the tablet and the bottom of the V-shaped opening on top will be minimal while still allowing for adequate manufacturability.

Having established the critical tablet weight, it was expected that compositions containing the active ingredient would tablet in an acceptable manner because acceptable tablets could be made at this composition using conventional tools. However, unexpectedly. it was found that a critical binder-lubricant relationship was needed to produce acceptable tablets with deep scoring tooling.

Four experiments were designed to select the most optimal tablet weight for the easy-break design. The data is shown in Example I.

EXAMPLE I TOTAL TABLET WEIGHT OPTIMIZATION All experiments were run in duplicates from one stock powder mixture and directly compressed on a rotary tablet press. The material run was an optimal placebo mixture as described below:

FORMULAE: A B C D Lactose hydrous U.S.P. qs qs qs qs Microcrystalline Cellulose 25 w/o 25 \\'/0 25 Wk) 25 w/o Magnesium Stearate U.S.P. 0.25 w/o 0.25 \\'/0 (L25 \\'/0 0.25 w/o Total Tablet Weight 230 mg 200 mg 175 mg 150 mg The harmaceutical term s is an abbreviation of P q EXAMPLE n the Latin phrase quantum sufficiat which means as much as suffices. The abbreviation w/o" means percent by weight.

The results were as follows: FORMULA A: Exhibits capping. high friability. in the Following the procedure of Example I a series of formulations were prepared and deeply scored tablets were made from them. The formulations are shown in Table I.

TABLE I PERCENT OF TOTAL TABLET WEIGHT FORMULA A B C D F G H l J K Microcr \'stalline Cellulose 25 25 25 45 45 25 25 25 60 *Solka-floc l0 Lactose. hydrous qs qs qs qs qs qs qs qs qs qs Lactose. anhydrous o3 Dicalcium Phosphate **Sta Rx I500 74 Magnesium Stearate 0.22 0.3 0.22 0.22 0.3 0.22 0.35 0.3 0.3 0.4 0.35 Stearic Acid ***Stero-Tex 0.50 Tale 2 lsosorbide Dinitrate Trituration 20.0 20.0 20.0 20.0 20.0 20.0 20.0 20.0 20.0 20.0 20.0

mg mg mg m mg mg mg mg mg mg mg Total Weight I75 mg 175 mg I75 mg 175 mg I75 mg 175 mg I75 mg I75 mg 175 mg 175 mg l75 mg Formulas A through H with the exception of G did not exhibit adequate manufacturabilit in a direct Compression process.

Purified Cellulose. Brown Co. Directly compressible starch ""Edible vegetable oil. powdered lubricant ranges of 7-15 Strong Cobb units (s.c.u.) hardness;

the friability was 2% 5 by Roche friabilator. FORMULA B: Repeated the behavior of Formula A on a somewhat reduced scale.

FORMULA C: Produced satisfactory tablet hardness of 8-14 s.c.u. and friability of 0.0% at that range. FORMULA D: Produced satisfactory tablets.

Initially it was tried to utilize a conventional isosorbide dinitrate formula and weight for the easy-break tableting tools. It was expected that the design would perform adequately at a total weight of 230 milligrams (mg). Surprisingly the tablets made at this weight were unsatisfactory. and evidenced capping. high friability in addition to insufficient tablet hardness. An attempt was made to solve the problem by selecting the most adequate tablet weight to achieve better manufacturability. but was unsuccessful.

The weight selection experiments indicated that in order to achieve adequate tableting parameters with deep scoring tooling the tablet weight will have to be under 200 mg. The optimum weight is about 175 mg because at 150 mg there is a high probability of tooling contact which in turn may cause damage to the punch tips.

Once the weight problem was solved, no further problems were anticipated. However, upon careful scrutiny of the tableting performance there was found an unexpected problem in the binder and lubricant relationship. Picking" and sticking were found in some cases. and soft tablets with capping in others. In order to resolve the problem a set of experiments was designed to determine the critical nature of the binder and lubricant levels. The experiments are shown in Example II:

Shown in Table I are drug amounts of 20 mg/tablet each. These correspond to a tablet containing 5 mg. of

isosorbide dinitrate which is utilized in a 25 weight percent mixture with lactose being weight percent.

To prepare a 10 mg. isosorbide dinitrate tablet 40 mg.

of drug-lactose mixture would be used (representing 10 mg. of isosorbide dinitrate). The change in dosage is balanced with the amount of lactose in the formulation while producing similar results. The results were as follows:

FORMULA A exhibited severe picking on the upper face of the tablet.

FORMULA B contained the mininal level of anhydrous lactose to produce an adequate tablet. However. the tablet demonstrated poor disintegration.

FORMULA C produced soft tablets that capped while still picking.

FORMULA D exhibited insufficient hardness range and picking on both tablet faces.

FORMULA E showed insufficient binding resulting in very soft tablets having high friability.

FORMULA F showed inadequate performance because of slight pick.

FORMULA G showed adequate manufacturability as to hardness and friability. The tablets were free of picking.

FORMULA H showed insufficient hardness with picking on bottom face.

FORMULA I was a slugged formula which exhibited binding and picking on the tablet lower face.

FORMULA J was a slugged formula with a higher lubricant level which produced adequate lubrication but insufficient hardness.

FORMULA K showed excellent manufacturability for all parameters.

5 Based on the foregoing it was determined that tablets made of conventional pharmaceutical ingredients would manufacture adequately at weights under 200 mg. utilizing a deeply scored design. In addition, a great amount of experimentation and design was spent on the 5 tablet formulation to overcome the critical nature of its binder and lubricant dependence. I

From the foregoing the preferred weight for deeply grooved tablets is 150 to 175 mg. The preferred ratio of lubricant to binder is obtained when the binder constitutes 45 to 99.7 w/o and the lubricant constitutes 0.3 to 0.4 'w/o of tablet exclusive of the amount of the active ingredient, fillers, extenders, flavor and the like. That is, the weight percent of the 'binder and lubricant is based on the portion of the tablet composition usually referred to as q.s..

Only microcrystalline cellulose of the binders presently available on the market has been found to be useful in deep grooved tablet compositions. Only the stearates, including stearic acid, of the lubricants prescrystalline cellulose with 0.35 percent by weight of magnesium stearate.

For assuring of distintegration and dissolution reproducibility the use of one 1) percent Amberlite is optional and has been tested to that effect.

The Mannitol U.S.P. used in the examples is the conventional powdered form rather than the granular form.

Formula H produced adequate tableting characteristics.

From the foregoing it was concluded that 10 mg. chewable tablets were successfully made in two formulations:

1. The first formulation uses a directly compressed mannitol and a dextrose and corn syrup solids granulation in combination;

2. The second formulation uses dextrose and corn syrupsolids granulation without mannitol in direct compression.

The choice between these two categories depends strictly on personal taste preference. Both formulae will produce similarly adequate results.

EXAMPLE Ill Preparation Of 10 Mg. lsosorbide Dinitrate Chewable Tablets The deeply scored design was also utilized in the manufacture of a chewable tablet form containing isosorbide dinitrate at a 10 mg. level.

Again, in this formula it was found necessary to resort to a lower tablet weight of 175 mg. In addition. because the design of a chewable tablet requires the incorporation of a chewable carrier. it was necessary to evaluate different chewable materials to obtain a suffrciently cohesive and well lubricated direct compression formula. The data obtained in those experiments is shown in Table II in which the tablets were prepared as described in Example I.

The preferred embodiment at which chewable deeply scored tablets can be-made is for the first category with TABLE II CHEWABLE TABLETS FORMULAE A B C D E F G H lsosorbide Dinitrate (25%) 40 mg 40 mg 40 mg 40.0 mg 40 mg 40 mg 40.0 mg 40.0 mg Lactose mixture *Nutab qs qs Mannitol U.S.P. qs 20% 20% 20% qs Cellutab. anhydrous 31.5% 3l.5% 3 l .5% qs Microcrystalline Cellulose 25.0% 20% 25% 25% 25% 25% 20% Solka floc 8.0% Magnesium Stearate U.S.P. 0.6% 0.7% l.()% [.0% 0.5% 0.9% 0.9%+0.9% 0.35% FD&C Yellow No. 5 Lake 0.1% 0.l% 0.4% 0.4% 0.4% 0.4% 0.4% 0.4% Sodium Saccharine NP. 0.08% 0.08% 0.08% 0.08% Methyl Cellulose 400 cps 0.7% Lemon Oil. spray dried l.7% l .7% l.7% l.7% l.7% l.7% Total Tablet Weight 222.5 I96 I90 175.0 l75 I75 I751) I75 mg mg mg mg mg mg mg mg Sucrose. invert sugar. starch. magnesium stearate direct compression granulation. "Dextrose and corn syrup solids granulation.

Formulae A, B, D, E and F are directly compressed.

Formula A exhibited very high friability, capping and a narrow hardness range.

In Formula B the weight has been reduced, but tablets still exhibit heavy capping and friability with very low hardness.

Formula C was a wet granulated formula, and exhibited high friability, capping and inadequate chewability due to the wet binder.

Formula D shows adequate manufacturability and chewability.

In Formula E reduced lubricant level results in heavy picking on both tablet faces.

In Formula F eliminating the sweetener from Formula D maintains adequate manufacturability with improved taste.

Formula G was slugged and exhibited capping. narrow hardness range and slight picking.

bility. presents additional variables to the ones already described above. When processing and formulating for such purpose, it is necessary to consider the properties producing the resulting chewable quality of the tablet, that is hardness, taste and pallatability. The majority of chewable carriers, apart from the granulated natural sugars and their derivatives, do 'not lend themselves to direct compression and tend'to lose some of their taste upon any granulation-method.

The examples illustrated in Table ll present the compositions of pharmaceutical tablets manufactured by three basic methods: direct compression. dry granulation. and wet granulation. These examples are not to be construed as limiting the scope of this invention which may only be determined by reference to the appended claims.

What is claimed is:

1. A chewable pharmaceutical tablet which is adequately imprinted with indicia or embossing and scored to form a groove which is V3 to /3 the depth of the total tablet thickness to facilitate separation into subdivisions containing substantially equal amounts of pharmaceutically active ingredient comprising a directly compressed formulation of; Y r

A. Active ingredient 5 to It) milligrams B. Microcrystalline Cellulose to percent F. The remainder being pharmaceutically acceptable fillers. extenders. flavoring and the like.

2. A tablet as defined in claim 1 in which the ingredients are present in the following amounts:

A. Microcrystalline cellulose .20 percent by weight 8. Dextrose and corn syrup 3L5 percent by solids granulation weight -continued C. Mannitol 25 percent by weight D. Magnesium stearate 1 percent by weight 3. A tablet as defined in claims 1 in which the total tablet weight is 150 to 175 milligrams.

4. A tablet as defined in claims 1 in which the total tablet weight is about 175 milligrams.

. 5. A tablet as defined in claim I in which the active ingredient is 10 milligrams of isosorbide dinitrate.

6. A chewable pharmaceutical tablet which is deeply adequately imprinted with indicia or embossing and scored to form a groove which is /3 to the depth of the total tablet thickness to facilitate separation into subdivisions containing substantially equal amount of a pharmaceutically active ingredient comprising a directly compressed formulation of:

Active ingredient fillers. extenders. flavoring and the like.

7. A tablet as defined in claim 6 in which the total tablet weight is 150 to 175 milligrams.

-8. A tablet as defined in claim' 6 in which the total tablet weight is 175 milligrams.

9. A tablet as defined in claim 6 in which the active ingredient is 10 milligrams of isosorbide dinitrate.

=l l l =l

Claims (9)

1. A CHEWABLE PHARMACEUTICAL TABLET WHICH IS ADEQUATELY IMPRINTED WITH INDICIA OR EMBOSSING AND SCORED TO FORM A GROOVE WHICH IS 1/3 TO 2/3 THE DEPTH OF THE TOTAL TABLET THICKNESS TO FACILITATE SEPARATION INTO SUBDIVISIONS CONTAINING SUBSTANTIALLY EQUAL AMOUNTS OF PHARMACEUTICALLY ACTIVE INGREDIENT COMPRISING A DIRECTLY COMPRESSED FORMULATION OF:
2. A tablet as defined in claim 1 in which the ingredients are present in the following amounts:
3. A tablet as defined in claims 1 in which the total tablet weight is 150 to 175 milligrams.
4. A tablet as defined in claims 1 in which the total tablet weight is about 175 milligrams.
5. A tablet as defined in claim 1 in which the active ingredient is 10 milligrams of isosorbide dinitrate.
6. A chewable pharmaceutical tablet which is deeply adequately imprinted with indicia or embossing and scored to form a groove which is 166 to 2/3 the depth of the total tablet thickness to facilitate separation into subdivisions containing substantially equal amount of a pharmaceutically active ingredient comprising a directly compressed formulation of:
7. A tablet as defined in claim 6 in which the total tablet weight is 150 to 175 milligrams.
8. A tablet as defined in claim 6 in which the total tablet weight is 175 milligrams.
9. A tablet as defined in claim 6 in which the active ingredient is 10 milligrams of isosorbide dinitrate.
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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4269859A (en) * 1979-04-19 1981-05-26 Brown Company Cellulose floc granules and process
US4863741A (en) * 1985-03-25 1989-09-05 Abbott Laboratories Tablet composition for drug combinations
US4874614A (en) * 1985-03-25 1989-10-17 Abbott Laboratories Pharmaceutical tableting method
GB2252043A (en) * 1991-01-23 1992-07-29 British Tech Group Controlled release compositions
US5279832A (en) * 1991-01-15 1994-01-18 Degussa Ag Active-substance preparation for oral administration, especially to ruminants
US6009690A (en) * 1994-12-23 2000-01-04 Basf Aktiengesellschaft Process and apparatus for the production of divisible tablets
US6132659A (en) * 1994-12-23 2000-10-17 Basf Aktiengesellschaft Production of lenticular tablets by melt calendering
US6488939B1 (en) 1998-12-04 2002-12-03 Abbott Laboratories Cleavable solid dosage forms and method for the production thereof
US20040076641A1 (en) * 2002-10-15 2004-04-22 Timothy Kershenstine Herbal dietary supplement
WO2005112870A1 (en) * 2004-05-21 2005-12-01 Accu-Break Pharmaceuticals, Inc. Pharmaceutical tablets having a separation mark positioned on the side of said tablets
US20070031494A1 (en) * 2004-05-21 2007-02-08 Lawrence Solomon Method of administering a partial dose using a segmented pharmaceutical tablet
WO2007104583A1 (en) * 2006-03-16 2007-09-20 Berlin-Chemie Ag Accurately divisible tablet
US20080233190A1 (en) * 2005-11-18 2008-09-25 Lawrence Solomon Segmented Pharmaceutical Dosage Forms
DE202008010089U1 (en) 2008-07-28 2008-10-16 Desitin Arzneimittel Gmbh Exactly divisible tablet

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Battista et al., Ind. Eng. Chem. 54(9): 20-29 (1962), "Microcrystalline Cellulose." *
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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4269859A (en) * 1979-04-19 1981-05-26 Brown Company Cellulose floc granules and process
US4863741A (en) * 1985-03-25 1989-09-05 Abbott Laboratories Tablet composition for drug combinations
US4874614A (en) * 1985-03-25 1989-10-17 Abbott Laboratories Pharmaceutical tableting method
US5279832A (en) * 1991-01-15 1994-01-18 Degussa Ag Active-substance preparation for oral administration, especially to ruminants
GB2252043A (en) * 1991-01-23 1992-07-29 British Tech Group Controlled release compositions
GB2252043B (en) * 1991-01-23 1994-10-12 British Tech Group Controlled release compositions
US6009690A (en) * 1994-12-23 2000-01-04 Basf Aktiengesellschaft Process and apparatus for the production of divisible tablets
US6132659A (en) * 1994-12-23 2000-10-17 Basf Aktiengesellschaft Production of lenticular tablets by melt calendering
US6488939B1 (en) 1998-12-04 2002-12-03 Abbott Laboratories Cleavable solid dosage forms and method for the production thereof
US20040076641A1 (en) * 2002-10-15 2004-04-22 Timothy Kershenstine Herbal dietary supplement
WO2005112870A1 (en) * 2004-05-21 2005-12-01 Accu-Break Pharmaceuticals, Inc. Pharmaceutical tablets having a separation mark positioned on the side of said tablets
US20070031494A1 (en) * 2004-05-21 2007-02-08 Lawrence Solomon Method of administering a partial dose using a segmented pharmaceutical tablet
US8158148B2 (en) 2004-05-21 2012-04-17 Accu-Break Technologies, Inc. Pharmaceutical tablets comprising two or more unitary segments
US20080199521A1 (en) * 2004-05-21 2008-08-21 Lawrence Solomon Scored Pharmaceutical Tablets Comprising A Plurality Of Secments
US20080233189A1 (en) * 2004-05-21 2008-09-25 Lawrence Solomon Pharmaceutical Tablets Comprising Two or More Unitary Segments
US7879352B2 (en) * 2004-05-21 2011-02-01 Accu-Break Technologies, Inc. Scored pharmaceutical tablets comprising a plurality of segments
US7838031B2 (en) 2004-05-21 2010-11-23 Lawrence Solomon Method of administering a partial dose using a segmented pharmaceutical tablet
US20080233190A1 (en) * 2005-11-18 2008-09-25 Lawrence Solomon Segmented Pharmaceutical Dosage Forms
US8231902B2 (en) * 2005-11-18 2012-07-31 Accu-Break Technologies, Inc. Segmented pharmaceutical dosage forms
WO2007104583A1 (en) * 2006-03-16 2007-09-20 Berlin-Chemie Ag Accurately divisible tablet
DE202008010089U1 (en) 2008-07-28 2008-10-16 Desitin Arzneimittel Gmbh Exactly divisible tablet

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