Title of Invention

IMMEDIATE RELEASE PHARMACEUTICAL TABLETS WITH HEIGHT GREATER THAN WIDTH

Abstract An immediate release compressed pharmaceutical tablet that has two or more segments and a top and a bottom and has a height that exceeds the width of the tablet. The height is measured vertically from the top to the bottom of the tablet while it is in the tablet die in which it is fully compressed, after compression has been completed. The width is measured as the greatest horizontal dimension of the tablet at a location halfway between the top and the bottom of the tablet, except that when the horizontal cross-section of the tablet is substantially rectangular, the width is defined by locating the two shorter sides of the perimeter of the horizontal cross-section, and measuring the length of a line that is at right angle to the shorter sides.
Full Text IMMEDIATE RELEASE PHARMACEUTICAL TABLETS WITH HEIGHT
GREATER THAN WIDTH
FIELD OF THE INVENTION
The invention provides immediate release non-homogeneous
compressed pharmaceutical tablets that are taller than they
are wide, said novel shape for immediate release tablets
resulting in previously undisclosed advantages with regard
to accurate breaking of the tablet so that breaking of the
tablet may more easily produce predictable quantities of
active ingredient(s).
BACKGROUND
Pharmaceutical tablets in divisible form containing an
indentation known as a score have long been known and
widely used. Problems with breaking scored tablets are
well-known. These problems include loss of active drug and
inaccurate division of the tablet, so that a tablet
intended to be divided into two equal half-tablets often
does not come close to that ideal.
Many drugs require dosage adjustments, such as warfarin,
the scored tablets of which are frequently broken. These
dosage adjustments through tablet breaking by patients have
been determined to be imprecise. As the following
discussion demonstrates, for many years experts have called
upon the pharmaceutical industry to improve the quality of
tablet breaking, yet such has not been optimized until the
current invention.


In 1984, Stimpel et al. ("Stimpel"), described the relative
accuracy of breaking of various tablets for treatment of
cardiovascular problems. M. Stimpel et al. , "Breaking
Tablets in Half." The Lancet (1984):1299. Even though
breaking was performed by a sophisticated, dexterous
person, Stimpel found that breaking was not accurate, and
opined that real world use by patients would provide yet
more unsatisfactory results. Stimpel called upon the
pharmaceutical industry to improve the accuracy of
splitting tablets: "Clearly any assumption that halving a
tablet will not lead to inaccurate doses is invalid. This
potential source of inaccuracy could be even more
significant in clinical situations (our study was done
under ideal conditions) and the pharmaceutical industry
should cackle it, either by improving divisibility (as
already has been done for lopressor and logroton) or, even
better, by marketing a wider range of unscored tablets to
provide all the doses that might be indicated clinically."
Despite that finding and statement, and despite the
issuance of various patents relating to optimizing a
scoring pattern and/or tablet shape, Rodenhuis et al. ,
(2004) noted that: "Improving the functioning of score
lines may be a more practical approach than banning this
dosage form" (emphasis added). N. Rodenhuis et al., "The
rationale of scored tablets as dosage form." European J. of
Pharmaceutical Sciences 21 (2004):305-308 (hereafter
"Rodenhuis"). Rodenhuis observed that European regulatory
authorities started a policy to discourage scoring of
tablets in 1998. This policy change, according to
Rodenhuis, likely related to "many recent reports of bad
functioning score lines" that "many scored tablets are

difficult to break," and that "many scored tablets show
unsatisfactory mass uniformity of the subdivided halves."
The authors then go on to describe useful aspects of
scoring tablets. For a comprehensive review article on
this topic, see van Santen, E., Barends, D.M. and Frijlink,
H.W. "Breaking of scored tablets: a review." European J. of
Pharmaceutics and Biopharmaceutics 53 (2002):139-145.
Some current studies that demonstrate the severity of the
problem are described below.
Peek et al . , (2002), studied tablet splitting by "elderly
patients" aged 50-79. Peek, B.T., Al-Achi, A., and Coombs,
S.J. "Accuracy of Tablet Splitting by Elderly Patients."
The Journal of the American Medical Association 288 No.4
(2002) : 139-145. Breaking scored tablets with mechanical
tablet splitters without specific instruction led to highly
unsatisfactory separating of the tablets. For example,
warfarin 5 mg was on average split into 1.9 and 3.1 mg
tablets. This potent anticoagulant has such a narrow
therapeutic range that 2, 2.5, and 3 mg tablet doses are
manufactured. Biron et al. , (1999), demonstrated that
warfarin 10 mg also often split to less than 4.25 or
greater than 5.75 mg. Biron, C, Liczner, P., Hansel, S.
and Schved, J.F., "Oral Anticoagulant Drugs: Do Not Cut
Tablets in Quarters." Thromb Haemost 1201 (1999). In
addition, they demonstrated that loss of mass due to
crumbling or chipping from the breaking of the warfarin
tablets was statistically significant. They also
demonstrated that quartering of the tablets was grossly
inaccurate.
McDevitt et al. , (1998), found that 25 mg unscored
hydrochlorothiazide tablets were manually split badly

enough that 12.4% deviated by more than 20% from ideal
weight. McDevitt, J.T., Gurst, A.H. and Chen, Y. "Accuracy
of Tablet Splitting." Pharmacotherapy 18 No.1 (1998):193-
197. 77% of the test subjects stated that they would be
willing to pay a premium for individually produced 12.5 mg
tablets rather than split 25 mg unscored tablets.
Rosenberg et al. , (2002), studied pharmacist-dispensed
split tablets. Rosenberg, J.M., Nathan, J.P. and
Plakogiannis, F. "Weight Variability of Pharmacist-
Dispensed Split Tablets." Journal of American
Pharmaceutical Association 42 No.2 (2002):200-205. They
found that "tablet splitting resulted in an unacceptably
high incidence of weight variation." They recommended that
"standards should be developed to ensure uniformity of
split tablets."
Teng et al . , (2002), using a trained individual in a
laboratory setting to split tablets, concluded that "the
majority of the 11 drug products we tested, when assessed
for their ability to be split into half-tablets of equal
dose, failed a liberally interpreted USP (United States
Pharmacopeia) uniformity test. . . The practice of dividing
tablets to save costs or to improve a dosage regimen .
is not recommended for patients using drugs with more
substantial toxicity and steep dose-response efficacy
curves." Teng, J., Song, C.K., Williams, R.L. and Polli,
J.E. "Lack of Medication Dose Uniformity in Commonly Split
Tablets." Journal of American Pharmaceutical Association 42
No. 2 (2002) :195-199.
Rodenhuis reported that 31% of all tablets in one
Netherlands study were subdivided before being swallowed.

In the U.S., "managed care" insurance organizations may
encourage splitting by patients of unscored tablets that
may not even have symmetrical shapes. Many drug products
in the US either are unscored tablets, or are provided as
capsules despite being able to be produced as tablets.
The invention is directed to amelioration of the problems
described above.
In addition, treatment with combination products is common
in pharmaceuticals, meaning that one dosage form may
contain more than one active ingredient. This means of
treatment may in part be discussed as follows:
A relevant field to the invention is the field of
combination drug therapy for systemic arterial hypertension
("hypertension"). Technically, combination therapy for
hypertension involves the use of two or more drugs on a
regular basis to treat a patient's hypertension.
Generally, this term implies daily treatment with at least
two drug products.
Combination therapy has long been used to treat
hypertension. It is widely estimated that approximately
halt of all cases of hypertension cannot be treated to goal
blood pressure with one drug at a maximally tolerated
dosage. To aid in treatment, solid oral dosage forms have
been produced that contain a plurality of active agents
within one tablet or capsule. These dosage forms are known
as "fixed-dose" combination products, because a patient or
pharmacist has no means of separating one active agent from
another. Sica, D., Drugs, 2002; 62 (3): "Rationale for
Fixed-Dose Combinations in the Treatment of Hypertension,"
states that "a considerable legacy, dating to the 1950's,

exists tor fixed-dose combination therapies." Later in the
same article, the author pinpoints a deficiency with the
fixed-dose approach, which embodiments of the current
invention largely correct: "A disadvantage to the use of
fixed-dose combination is a lack of dose administration
flexibility for its individual components, although it is
uncommon for physicians to maximally exploit the dose
administration flexibility inherent to the use of free
combinations. With fixed-dose combination therapy, if
conditional amounts of either drug are required for BP
control, a separate prescription will be required. This
increases complexity of the regimen and has the potential
to negatively affect compliance. In addition, fixed-dose
combination therapy may not provide adequate drug amounts
to manage illnesses, such as angina or congestive heart
failure, which commonly co-exist with hypertension."
The invention provides a means to improve the above

Situation, by allowing flexibility of dosing within a
combination dosage form.
The current invention describes a tablet shape adapted for
separating one vertically disposed segment from another.
In the large field of immediate release pharmaceuticals,
the relative dimensions of the tablet are novel
Commercially, the only product that as produced is taller
than it is wide is Concerta®, which is a three-segment
tablet, two of which segments are devoted to controlled
release of the active drug, methylphenidate. Concerta
utilizes the OROS® system, which utilizes the taller-than-
wide geometry as part of its controlled release
characteristics. The manufacturer's directions for the use
of Concerta specify that the tablets should never be

broken.
Except for Concerta, tablets, including those involving
layers vertically disposed one on the other, have been
produced wider than they are tall.
A tablet press manufacturer, Korsch AG of Germany, has
developed a tablet press that can produce up to five
vertically disposed layers. It has been utilized to
produce taller-than-wide five-layer tablets having no
active drugs therein and has also been used to manufacture
Concerta.
SUMMARY OF THE INVENTION
The invention is directed to an immediate release
compressed pharmaceutical tablet that has two or more
segments, has a top and a bottom, and has a height that
exceeds the width of said tablet, said height being
measured vertically from the top to the bottom of said
tablet while it is in the tablet die in which it is fully
compressed, after said compression has been completed; and
said width being measured as the greatest horizontal
dimension of the tablet at a location halfway between said
top and said bottom of said tablet, except that when the
horizontal cross-section of said tablet is substantially
rectangular, the width is defined by locating the two
shorter sides of the perimeter of said horizontal cross-
section, and measuring the length of a line that is at
right angle to said shorter sides.
A preferred embodiment of the immediate release compressed

pharmaceutical tablet is one that comprises two or more
segments disposed one above the other.
The invention contemplates immediate release
pharmaceutical tablets, preferably containing a .
pharmacologically effective quantity of a drug, where the
height of the tablet (vertical dimension) exceeds its width
(horizontally dimension); i.e., the tablet is taller than
it is wide. The terms "vertical" and "horizontal"
("horizontal" is also referred to as "transverse") axis of
the tablets of the invention are determined by and have the
same orientation as that of the tablet die in which the
tablet: is compressed in a tablet press or other tabletting
machine ("tablet press" herein), and the order of entry of
granulations into the die.
Tablets of the invention are most preferably produced for
commercial sale in a high-speed tabletting machine.
Tablets are produced in a die of said tabletting machine.
In such a machine, granulations enter the tablet die one on
top o£ another, so that said granulations are said to be
vertically disposed to each other. Layers and segments
formed from vertically disposed granulations are considered
to be vertically disposed, as well. The height
("tallness") of a tablet is measured as the vertical
distance between the lowest part of the first granulation
to enter the die to the highest part of the last
granulation to enter the die (said first granulation forms
the bottom layer and said last granulation forms the top
layer).

The width is a horizontal (transverse) dimension. In
determining the width, diagonal measurements are not taken
through the horizontal aspect of the tablet if the tablet
is substantially rectangular in transverse cross-section:
If the perimeter of the horizontal aspect of the tablet
were rectangular (and not square) , then the width of the
tablet would be the greater of the two perimeter
measurements as is typically used to describe a rectangle,
and not the diagonal that is calculated by the Pythagorean
theorem and that uses said perimeter measurements to
calculate said diagonal. Similarly, tablets with a
substantially rectangular vertical cross-sectional
configuration have a height that is measured as a perimeter
and not; a diagonal measurement. When a vertical or
horizontal cross-sectional configuration is not
substantially rectangular, which includes triangles,
rhombi, and hexagons, the greatest dimension through said
cross-uection represents said height or width.
Many of the preferred tablets of the invention utilize
segments that lack a pharmacologically effective dose of a
drug to serve as a region for breaking if an art accurated
partial dose of drug found in the whole tablet is desired.
By convention herein, the term "contains a drug," when used
to refer to a granulation, layer, or segment of a tablet,
said granulation, layer, or segment has within it a
pharmacologically effective dose of a drug. The term
"contain a drug" when used to refer to a plurality of
granulations, layers or segments , such as two granulations
or two segments, means that said granulations, layers etc.
have within them a pharmacologically effective dose of a
drug. The term "contain a drug or drugs" when used to
refer to a granulation, layer, or segment means that said

granulation, layer or segment may contain either a single
drug or a specific ratio of a plurality of drugs. When
"contain a drug or drugs" is used' to refer to a plurality
of segments, layers, or granulations, that term means that
the plurality of granulations, layers or segments may
contain either a single drug or a specific ratio of a
plurality of drugs.
A layer or segment, but not a granulation, is said to "lack
a drug (or drugs)" if said layer or segment either contains
none of said drug (or drugs) or contains a
pharmacologically ineffective amount of said drug.
Parts of speech, such as "contain" "contains" "containing,"
and "lacking" in relation to the above two paragraphs also
are terms of art with otherwise the same meanings to those
described therein.
In preferred embodiments, but without limitation, the
invention comprises compressed immediate release
pharmaceutical tablets where one or more drugs are disposed
in segments where:
(a) said tablet includes two or more segments that contain
the same drug or drugs in the same or different
concentrations relative to the excipients found in said
segments, and the tablet is not provided with another drug
than is found in said segments; or
(b) said tablet includes two or more segments, each segment
of which contains a different drug or drugs;
(c) said tablet includes a first segment containing a drug
or drugs; a second segment; and a third segment containing
a drugs or drugs which are different from the drug or drugs

in said first segment, said second segment being interposed
between said first and said third segment (i.e., below one
of said segments and above the other) and said second
segment lacks said drug or drugs.
(d) said tablet includes a first segment containing a
drug or drugs; a second segment; and a third segment
containing the same drug as the drug in said first
segment, said second segment being interposed between said
first and said third segment, and said second segment
lacking said drug or drugs.
In a more preferred embodiment, the tablets of the
invention have at least two compositionally distinct
segments, with a first segment containing an active drug or
drugs in a pharmacologically effective amount and a second
segment that:
(a) contains the same drug at a lower concentration than
the concentration of said drug in said first segment, or
contains the same ratio of the drugs in said segment; or
(b) lacks said drug or drugs present in said first segment
and the tablet also has a third segment containing the same
drug that is present in said first segment; or
(c) lacks said drug or drugs in said first segment, and
said tablet also has a third segment containing a drug or
drugs different from any in said first segment, wherein
said first and third segments are chemically and physically
compatible; or
(d) has a different drug than the drug in said first
segment and also includes a third segment containing the
same drug that is present in said first segment.
A further preferred embodiment may optionally contain such
guidelines for tablet breaking as a score, indicia, printed

indicia, a perforation, contrasting color segments, and the
like on or in the side of the tablet, with a score
preferably being substantially horizontal to allow tablet
breaking only through one segment or an interface between
segments. A side of a tablet is an external part of said
tablet that has a vertical part that is substantially
parallel to the theoretical vertical axis of the tablet; a
side is in contact with the inner wall or face of the
tablet die in which said tablet is compressed.
Taller than wide tablets of the invention are shaped to be
more easily broken through the tablet's theoretical
vertical axis (i.e., in a horizontal direction) than are
conventional, currently-manufactured tablets having a
"wider than tall" configuration. Many preferred uses of
tablets of the invention are to break through an interposed
segment of the tablet lacking a pharmacologically effective
dose of a drug without breaking through a segment above or
below said interposed segment.
It is a primary object of the invention to provide an
immediate release pharmaceutical tablet that may be easily
broken to provide a partial dose of a drug or drugs that is
contained in said tablet.
It is also an object of the invention to provide an
immediate release pharmaceutical tablet having three
segments, one of which is an interposed segment which is
adapted to be broken through in such a manner as to keep
the segments between which it is interposed and that
contain pharmacologically effective quantities of a drug or
drugs substantially intact if said tablet is broken through
said interposed segment.

These and other objects of the invention will become
apparent from the present application.

RIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE ACCOMPANYING DRAWINGS

Fig. 1a is a cross-section of a taller than wide tablet
looking towards the side of the tablet having a score;
Fig. 1b is a cross-section of the tablet of Fig. 1a looking
at the side of the tablet where the score ends;
Figs 2a-d are views of Fig la and Fig. lb respectively
when the tablets have been broken through the score.
Fig. 3 is a cross-section of a taller than wide tablet
having two segments, one of which is about three-quarters
of the length of the tablet.
Figs. 4 a -b are views of Fig. 3 when the tablet has been
broken at the approximate mid-point of the tablet.
Fig. 5 is a cross-section of a taller than wide tablet
having five segments.
Figs 6a-b are views of Fig. 5 when the tablet has been
broken through one segment.
Figs. 7a-c are views of Fig. 5 when the tablet has
effectively been broken through two segments in two steps,
first by breaking the tablet and then by breaking the
tablette of Fig. 6b.
Fig. 8 is a cross-section of a tablet that is wider than it
is tall and that has two segments.
DETAILED DESCRIPTION OF THE INVENTION
Tablets of the invention are preferably those compressed in
a tablet press. For commercial use, a high-speed three
(3)- or five (5)-station press produced by Korsch AG may be
utilized. Remington's Pharmaceutical Sciences 20th Ed.,
Mack Publishing Co., Easton, Pa. (2000), Chapter 45, which
is incorporated by reference, describes the various
techniques utilized in making compressed tablets. The

tablets of the invention are primarily intended for oral
admirn stration but they may also be used for other
applications. Tablets of the invention are not formed
using a cement, glue, adhesive, or the like, and are
preferably uncoated.
The tablets of the invention will comprise at least two
compositionally different segments.
A segment represents the entirety of a contiguous,
substantially homogeneous part of a tablet or tablette (see
below) of the invention. If two or more consecutive
granulations entering the die are substantially identical,
then when compressed, they will form one segment. Such a
segment is a sub-type of segment that may be referred to
specifically as a compound segment. If, however, two
substantially non-identical granulations (such as those
containing different active drugs, the same active drugs in
different ratios, different excipients or different ratios
of similar excipients, or different salts of the same
active drug) were compressed onto each other, they would
comprise two segments. Granulations comprising the same
active drug in the same concentration relative to
excipients but with dissimilar excipients would comprise
two segments if one granulation were compressed onto
another.
A layer is produced by introducing an amount of an
individual granulation into a tablet die to fill at least a
part of the die. A layer is considered to be present
whether it is the form of an un-tamped, tamped or fully
compressed granulation.

In many of the most preferred tablets of the invention, a
layer, (and the granulation from which it is derived), will
not need to be placed on top of or below (e.g., adjoining,
or contiguous with) a substantially identical layer (or
granulation) . In such a case, one layer will give- rise to
the sub-type of segment that is a simple segment. The use
of the term "segment" allows a segment to be simple or
compound.
Because the tablets of the invention have been adapted to
be broken if and when desired, it has proven useful to
develop a term for the major fragments of said breaking.
The inventors use the term "tablette" in this regard. An
example of tablette formation is as follows. A standard
single-scored, mono-layer, homogeneous pharmaceutical
tablet is broken. Said breaking produces two major
fragments, each of which is called a tablette, generally
plus some chips and crumbling which are preferably minor in
amount. In the segmented, layered tablets of the
invention, to utilize the invention properly may make it
advantageous to place a score transversely into a segment,
such as an inner segment, as may be done with an instrument
such as a file. Successfully breaking said tablet through
said score will result in two tablettes, representing the
two major fragments of the tablet and not including smaller
fragments such as crumbs or chips. The accompanying
diagrams help clarify the relationship of tablets to
tablettes.
The terms "active agent," "drug," "active drug," active
pharmaceutical agent," "pharmacologically active agent" are
interchangeable and include, without limitation,
prescription and non-prescription pharmaceutical compounds,

as well as pharmacologically effective doses of vitamins,
cofactors, and the like. Substances such as foodstuffs,
vitamins in "recommended daily allow" quantities, and the
like are not considered to be "drugs" herein.
The term "undetectable amount" means that using
conventional analytical techniques such as high performance
liquid chromatography (HPLC), nuclear magnetic resonance
imaging (NMRI), and the like, the presence of an active
compound can not be identified. The term "pharmacologically
ineffective amount" means an amount of a drug or drugs that
has or have no measurable pharmacological effect. Due to
the conditions under which high speed automated tabletting
equipment are operated, mixing of different granulations
may occur during tablet formation which may cause material
such as drug substance present in one granulation to appear
in a layer or segment where it was not intended to be
placed.
The term "relatively inactive segment" refers to a segment
that either contains an undetectable amount of any drug or
contains a diminished concentration of any
pharmacologically effective drug or drugs contained in
another segment or segments.
The terminology used herein is for the purpose of providing
a general understanding and is not intended to be limiting.
As an example of a method of manufacture of a preferred
tablet of the invention, first, a granulation containing a
pharmacologically effective dose of a drug enters the die
and is tamped. Second, a granulation lacking a drug (an
"inactive granulation") enters the die and is tamped.

Optionally, another inactive granulation lacking active
drug also enters the die and is tamped. The inactive
granulation (s) creates a part of the tablet that can be
identified and broken through so that a part of the drug
containing a significant concentration of drug is not
broken through. Last, a second granulation containing a
pharmacologically effective quantity of a drug enters the
die, is optionally tamped, and then final compression to
form a compressed tablet occurs. While one or all segments
may individually have a width greater than height, the
tablet as a whole has a height that exceeds its width.
Subsequent to tablet formation, optionally a score may be
placed in the side of said tablet, preferably transversely.
Alternatively, after tablet formation, a printed line or
other forms of indicia such as dotted lines, symbols or
perforations may be placed on or in the surface of the
tablet, all of which serve the purpose of allowing
identification of said tablet's desired breaking region
from the standpoint of effecting accurate separation of the
parts of a tablet containing isolated doses of drug. Other
means ot aiding identification of a region of potentially
desired tablet breaking may be utilized such as the use of
contrasting colors in different segments.
Suitable dimensions for tablets according to the invention
are; height: 6 to 24 mm; preferably 10 to 18 mm and more
preferably from 10 to 14 mm; width (at the widest dimension
of the horizontal axis) : 2 to 16mm; preferably 3 to 10 mm
and more preferably 4 to 8 mm. Without limitation, the
dimensions of the tablet may be optimal if the ratio of the
height to the width is between about 1.5:1 to about 3:1.
Numerous other structures may be created, some of which are

further delineated below. Various advantages in the
treatment: of human patients and other animals in need are
created by tablets of the shape described.
Tablets of the invention are most preferably formed in a
high-speed tablet press. In a typical manufacturing
procedure, two or more different granulations are
separately fed into a die, utilizing different filling
stations. Wet granulations are often preferred to limit
transfer of material from one granulation to another.
Direct compression of powder is also a preferred
manufacturing technique.
Full entry of a granulation at a filling station produces a
layer. Tablets of the invention have a layered structure.
It may be relevant to add two consecutive substantially
identical inactive granulations to form two identical,
contiguous layers. After compression, the part of the
tablet formed by said two identical granulations is
referred to as a segment. The type of segment so formed is
called a compound segment. There also may, in the case in
which a large quantity of an active ingredient is desired
to be in one segment, be cause to have two substantially
identical granulations containing said active ingredient to
enter at two consecutive filling stations, thus producing,
after final compression to form a tablet, a compound
segment that contains active drug. The more common case is
that in which a first granulation enters the die not on top
of a substantially identical granulation (layer), forms a
layer, and a substantially non-identical (i.e., different)
granulation next enters said die, so that said first
granulation forms a layer that is not contiguous with a

substantially identical layer. Said first granulation
form;; a layer that is considered to be a simple segment in
the compressed tablet.
The benefits of the invention include the utilization
preferably of inactive granulations, and less preferably,
segments with diminished concentration of a drug relative
to another segment. Optimally the tablet is provided with
a means of identifying an optimal breaking region and of
identifying one tablette from another after tablet
breaking, an important benefit if the tablettes contain
different, types or quantities of a drug or drugs.
Because of the novelty of the tablets, it is necessary to
describe the top, bottom, sides, etc. of the tablet. It
has been found best to describe the tablet with regard to
such terms based on said tablet's formation and location in
the die in which said tablet is formed.
As used herein, such terms as "horizontal" ("transverse")
and "vertical" when used in relation to a tablet, are based
on the spatial orientation of the tablet as, and after, it
is produced in a die, but before removal or ejection from
the die. Current methods of manufacture produce tablets
with one granulation entering the die on top of another, so
that tablets of the invention produced in such a manner
comprise one or more top (outer) segments, one or more
bottom (outer) segments, and optionally one or more middle
(inner) segments. A segment that is not a top or bottom
(collectively, "outer") segment is considered to be an
inner segment, even though of course an inner segment has
an external aspect. The number of inner segments is not
limited.

The bottom segment of a tablet contains the first
granulation into the die. The top segment of a tablet
contains the last granulation to enter the die. A "side"
of the tablet refers to that external part of said tablet
in contact with the internal vertical face or aspect of the
tablet die in which said tablet is produced. Typically,
sides of the tablets of the invention are vertically
oriented, in contrast to the tops and bottoms of the
invention. In the case of cupping and beveling of the top
of the tablet, which may from time to time be extensive,
the tablet's side is considered to also include the
external part of the tablet that was in contact with the
internal vertical face or aspect of the tablet die before a
top punch formed said cupping, beveling, or the like.
If separate granulations were to be sequentially placed in
a die horizontally (side-to-side) and not vertically as is
currently the practice, then the tablets so produced would
be within the scope of the present invention as the same
product would be produced. When the tablet of Fig. 1, for
example, is laid on a flat table, it will tend to lie
lengthwise at right angles to the manner in which it is
formed in the die (i.e., its longest axis would lie
horizontally in relation to the tabletop) , so that if the
three segments were all different colors, then the segments
would appear to be arranged not vertically (one on top of
the other), but rather horizontally (side-to-side). For
consistency of terminology, such segments nonetheless are
considered herein to be disposed vertically on top of each
other, because of the manner in which they were created.

The major advantage of the invention is that it optimizes
optional tablet breaking. When force is applied to break a
tablet, breaking of the tablet tends to more easily produce
predictable quantities of active ingredient(s) in tablettes
than "wider than tall" tablets with segments containing the
same quantities of drugs. The tablet may be broken
according to the invention either by applying force such as
a cutting edge directly to the region to be broken through,
or to outer segments, potentially in either case breaking
through an inner segment.
Examples of: specific embodiments of the invention are best
described with reference to the drawings. Shaded areas
represent segments derived from active granulations, i.e.,
those which contain a drug; clear (plain) areas represent
segments derived from inactive granulations, i.e., those
formulated with no active drug.
The drawings depict vertical cross-sectional views of
tablets and tablettes of the invention. Tablets are
depicted as if they were in the die, so that the top of the
tablet as it is oriented on the page corresponds with the
top of the tablet in the die. In other words, the top
segment. of the tablet as viewed contains the last
granulation to enter the die. Tablettes are depicted as
they would have been in the die before they were separated
from the intact tablet.
"Front views" refer to a cross-sectional view of a tablet
that has a theoretical geometric plane passed through the
tablet relative to a side which is arbitrarily designated
as the tront. Figures labeled as "side view," which also
have a corresponding "front view" are taken as a cross-
section through the whole tablet from the right side of a

front view i.e., a side view is a cross-section that is
taken by passing a plane through the vertical axis of the
whole tablet at a 90o angle to the cross-sectional front
view. Each front view represents a schematic cross-section
that passes through the midpoint of the horizontal cross-
section a:; measured from the front of the tablet to the
back of the tablet or tablette. The front view is also
parallel to the major axis of the tablet (e.g., for a
tablet with a rectangular (but not square) transverse
cross-section, the longer side of the perimeter is parallel
with the plane that depicts the cross-sectional, front
view.
That plane is located half-way between the front and back
surfaces of said tablet. The side views of Figs, 1a-b and
2a-b are taken from a vertically-oriented plane that passes
through the midpoint of the longer transverse dimension
(i.e., the width), and thus are located at and
perpendicular to the mid-point of the front view. Drawings
are of tablets that have a rectangular but not square
horizontal cross-section at the vertical mid-point of the
tablet.
Segments containing pharmacologically active amounts of a
drug or drugs are shown crosshatched; pharmacologically
ineffective segments are shown plain (clear, without
crosshatching or stippling) . The upper part of each figure
corresponds to the upper part of a tablet, all of which are
depicted as they are situated within a die after final
compression and before ejection from the die. For
consistency, tablettes are depicted in the same orientation
as the tablets from which they are formed, although
tablettes are created after tablet ejection from the die.
Dotted lines in the tablets depicted in the Figures may
represent printed marks or other indicia, or scores that
are present on or in the surface of the tablet and, if they
represent a score, said score does not extend deeply enough

into the tablet to appear in the cross-sectional front
view. TIT; transverse dotted lines reflecting scores shown
in the Figures imply no intention to limit the depth of any
scores of the tablets of the invention. Horizontal dotted
lines on the front views that represent the surface scores
are schematic, and do not necessarily represent the full
vertical extent of a score, printed mark, or the like.
Tablettes are depicted with broken surfaces as indicated by
a fine saw-tooth pattern. Such saw-tooth depiction is
schematic and not intended to represent the actual pattern
of breaking of a tablet (or tablette, which often leads to
irregular edges even if said tablet is broken through a
score.
Grasping and breaking said tablet is easier with the
current , taller-than-wider design than would be the case
under layered (segmented) tablets known to the art, in
which breaking a tablet through one segment only, if
feasible, would require "filleting" the tablet through its
longest axis.
Figures 1a and lb depict a tablet with compositionally
substantially identical upper segment 40 and lower segment
44. Inner segment 42 contains trace amounts of the drug
that is present in a therapeutically effective quantity in
each OL segments 40 and 44. Interfaces 46 and 48 represent
regions in which the upper part of segment 42 and the lower
part: of segment 42 respectively adjbin upper segment 40 and
lower segment 44. The curved interfaces result from the
profile of the upper tablet punch which is curved. Score
52 is depicted in Fig. lb. Dotted line 50 in Fig. la is a
reflection of score 52 on the surface of the tablet (not

shown that does not penetrate half-way through the
shorten transverse axis of the tablet.
Figs. 2a-d depict tablettes formed from breaking the tablet
of Figs, 1a and 1b through score 52. Inner segment 42 of
Fig. 1a no longer exists as an intact segment. The upper
tablette of Figs. 1a and 1c contains segment 80 that
adjoins intact upper segment 40 and the lower tablette
contains segment 82 and intact segment 44.
Breaking the tablet of Fig. la and lb through the score
placed in segment 42 is clearly easier than breaking the
tablet through its vertical dimension, which is currently
the practice with scored layered (segmented) tablets. The
fact that no break is made in the parts of the tablet where
the active drug has been placed provides for exceptionally
accurate breaking relative to the active drug or drugs
contained in the tablet.
Fig. 3 demonstrates a two-segment tablet, each segment
formed from a granulation containing a pharmacologically
effective amount of medication. Upper, (outer) segment 124
is larger than lower (outer) segment 126. Interface 128
indicates a region at which said segments are contiguous.
A printed mark on the outer surface of the tablet (not
shown) indicates a desired breaking point, as indicated by
the location of arrow 130 that reflects the position of
said surface printed mark. The two segments also have
different color, however, further allowing identification
of which part of the tablet contains which segment.
Figs. 4a and 4b depict the two tablettes formed by breaking
the tablet of Fig. 3. The tablette of Fig. 4a consists of

segment. 110, which represents the bulk of segment 124 of
Fig. 3. The tablette depicted in Fig. 4b contains segment
112 in an intact form and segment 120, which represents a
less than half-portion of segment 126 of Fig. 3. Interface
116 indicates a region at which said segments are
contiguous. The curved face is due to the profile of the
tablet punch.
Fig. 5 illustrates a tablet more elongated than those
previously demonstrated. Said tablet is adapted, even more
than the others, for ease of breaking through one segment.
Upper segment 600 is provided with a therapeutic quantity
of a drug; stippled inner segment 604 is provided with a
therapeutic quantity of a different drug; and, lower
segment 608 is provided with a therapeutic quantity of a
drug different from that found in a therapeutic quantity in
segments 600 and 604. Clear (plain) inner segments 602 and
606 contain pharmacologically ineffective amounts of each
of the three drugs found in the tablet. Interfaces 610,
612, 614, and 616 represent the regions at which two
contiguous segments adjoin. The tablet of Fig. 5 is
provided with a different color for each segment. Even
though there is no surface scoring or indicia, the color
scheme in such that a person's attention may be directed to
apply force to break the tablet through segment 602 to
create the tablettes depicted in Figs. 6a and 6b. Fig. 6a
depicts the smaller tablette created by breaking the tablet
of Fig. 5 through segment 602 in a transverse fashion.
Segment 620 has been created by said breaking, and segment
602 of Fig. 5 no longer exists as an intact segment. Fig.
6b depicts the larger tablette created by said breaking of
the tablet of Fig. 5. New upper segment 622 has been
created.

Figs. 7a-c depict three tablettes created by the subsequent
breaking ol the tablette of Fig. 6b. New segment 630 and
segment 6 32 have been created and segment 606 no longer
exists as an intact segment.
Fig. 8 depicts a traditional two-segment tablet. In this
tablet, lower (bottom) segment 324 contains a drug
different from that contained in upper (top) part 322.
Score 328 indents segment 324. Interface 326 is present at
the region at which segments 322 and 324 meet. The tablet
of Fig. 8 is not a tablet of the invention. It depicts a
schematic of a tablet of the prior art of bilayer tablets.
One may readily appreciate the difficulty inherent in
attempting to break a tablet such as the tablet of Fig. 8
horizontally, through one segment only, or, analogously, a
tablet similar to that of Fig. 8 but that in addition was
provided with, say, a segment below that of segment 324.
Benefits of the invention are not limited to tablets of any
specific number of active ingredients. All segments
containing an active ingredient may contain the same drug,
or segments may contain different drugs.
In order to fully realize the benefits of the invention, a
score may be placed into a segment (or interface between
segments) of the tablet. This score may be formed in an
inner segment with a file in a substantially horizontal
mariner, so that breaking the tablet through said score
could lead to breaking through the inner segment while
leaving the outer segments intact.
In addition, similar means of marking tablets may be

followed such as by causing an edible ink to be placed on
the tablets, thus delineating a desired region of the
tablet, such as its middle segment. Such application is
well known in the art. Other means of applying indicia are
contemplated as within the scope of the invention.
DESCRIPTION OF MANUFACTURING PREFERRED EMBODIMENTS
A "taller than wide" tablet is made which has three
segments, each with an active top or upper segment and an
active lower or bottom segment separated by a substantially
inactive middle segment. A Stokes 27-station tri-layer
rotary tablet press is used. All formulations are directly
compressible powder blends. The blending both of the
amlodipino formulation and the benazepril formulation are
performed in a Patterson-Kelly "V" blender. The middle
segment consists of 194 mg of Nu-Tab® and requires no
blending. The tablets are compressed using 0.131 inch by
0.3222 inch oval, concave tablet punches to a hardness of
35 kiloponds. The bottom segment is introduced first into
the die. The tablet weight is 310 mg. Tablets so made are
8 mm tall; the inactive middle segment varies from 5-6 mm
in height and a width of 4mm. Weights in mg of the
granulation comprising each segment are as follow:


Manufacturing Instructions
1. Weigh each ingredient.
2. Screen each ingredient.
3. Triturate the color with the major diluent in
geometric proportions using a suitable mixer.
4. Add the remaining ingredients, except the lubricant,
to the color mixer from step #3 and mix for desired
time .
5. Add the lubricant to the blend from Step #4 and mix
for desired time.
6. Add the blend to a suitable press fitted with the
desired tooling and compress into tablets.


Manufacturing Instructions
1. Weigh each ingredient.
2. Screen each ingredient.
3. Triturate the color with the major diluent in
geometric proportions using a suitable mixer.
4 Add the remaining ingredients, except the lubricant,
to the color mixer from step #3 and mix for desired
time.
5. Add the lubricant to the blend from Step #4 and mix
for desired time.
6. Add the blend to a suitable press fitted with the
desired tooling and compress into tablets.
Tabletting Instructions
1. Place the powder for active layer in hopper #1.
2. Place the powder for placebo layer in hopper #2.
3. Place the powder for active layer in hopper #3.
4. Compress layer #1 tablets to desired weight (tablets
for layer #1 should form a soft compact).
5. Compress layer #1 & Layer #2 tablets to desired
combined weight of layer #1 and layer #2 weight
(tablets should form a soft compact).
6. Compress the tri- layer tablet to the desired total
tablet weight (layer #1 weight + layer #2 weight +
layer #3 weight) Tablet should be at desired hardness.
A similar tablet of the invention is separately
produced using the same top and bottom segments as the
above, but using the following ingredients instead of Nu-
Tab for the middle segment. The following are blended


Manufacturing Instructions
1. Weigh each ingredient.
2. Screen each ingredient.
3. Place all of the ingredients, except the lubricant,
into a suitable mixer and mix for desired time.
4. Add the lubricant to the blend from Step #3 and mix
for desired time.
5. Add the blend to a suitable press fitted with the
desired tooling and compress into tablets.
The tablets were compressed using oval 0.131 inch by 0.3222
inch, concave tablet punches to a hardness of 35 kiloponds.
The bottom segment was introduced first into the die. The
tablet weight was 280 mg. Tablets with said middle segment
were 6 mm high, and the inactive middle segment was 3.5-4
mm high.

Tabletting Instructions
1. Place the powder for active layer in hopper #1.
2 . Place the powder for placebo layer in hopper #2.
3. Place the powder for active layer in hopper #3.
4. Compress layer #1 tablets to desired weight (tablets
for layer #1 should form a soft compact).
5. Compress layer #1 & Layer #2 tablets to desired
combined weight of layer #1 and layer #2 weight
(tablets should form a soft compact).
6. Compress the tri-layer tablet to the desired total
tablet weight (layer #1 weight + layer #2 weight +
layer #3 weight) Tablet should be at desired hardness.
In a similar way, other taller than wide tablets can be
made on a tablet press, such as, the Korsch TRP900 which
can produce taller tablets due to its design for deep
filling cams which allow for deeper fills and greater
distances between the upper and lower compression tools.
To make an oval 0.131 inch by 0.3222 inch, concave tablet
that is 12mm tall on the Korsch TRP900 the formulator
would have to increase the weight of the inactive Nu-Tab®
middle segment to about 323mg. Similarly to have a
finished tablet height of 14mm the tablet would be
formulated with a middle segment weighing about 3 88mg.
If the formulator preferred, they could use the second
example for a middle layer, i.e., the dibasic calcium
phosphate (DCP) formulation. In such a case making an
oval 0.131 inch by 0.3222 inch, concave tablet that is
12mm tall on the Korsch TRP900 the formulator would have
to increase the weight of the inactive DCP middle segment
to about 410mg. Similarly to have a finished tablet

height of 14mm the tablet would be formulated with a
middle segment weighing about 4 92mg.
*****
The invention also includes the method of administering one
or more drugs via the dosage forms such as tablets and
tablettes of the invention to a patient, mammal, or other
animal in need of pharmaceuticals for the prevention or
treatment of an illness, maintenance of good health,
retarding of aging, or other purpose. Included are methods
of treating a patient with only one drug from a combination
product, such as with a novel tablette of the invention,
enabling downward dose adjustment for a variety of reasons;
or, in a similar vein, a patient may be treated with one
whole tablet containing a plurality of active drugs and in
addition receive only one drug from a similar tablet, thus
enabling upward dose adjustment. Combination products that
can benefit from the invention, in which one drug is in an
outer active segment, and a second and different drug is in
the other outer active segment, and an inactive middle
segment as in embodiments such as was described in
paragraphs 3 and 4 above, include those containing the
following pairs of drugs: amlodipine and either benazepril,
chlorthalidone, or atorvastatin; benazepril and
hydrochlorothiazide; olmesartan and hydrochlorothiazide;
and many others, including the majority of the currently-
produced combination products. Also included is the method
of treating a patient with a precise partial dose of
medication from a whole tablet, which may be a half or
quarter of the whole dose, but may usefully be a different
fraction. Warfarin especially may usefully be produced and
dosed according to the invention with separable segments of
the tablet that may but need not be as halves, quarters,
etc. L-thyroxine and digoxin are other examples that could

so benefit, along with warfarin.
The following give possible clinical situations in which
the tablets of the invention could provide important
benefits.
1. A currently marketed product in the United States is
Caduet®, which contains the active ingredients atorvastatin
calcium (atorvastatin) and amlodipine besylate (amlodipine)
which are largely homogeneously interdispersed in an
unscored tablet. The product is indicated to treat both
hyperlipidemia (atorvastatin) and hypertension
(amlodipine). A patient ingesting this tablet daily may
then undergo a blood test and be diagnosed as having liver
dysfunction as manifested by elevation of an enzyme's
concentration in the blood. The physician may then
recommend cessation, possibly temporary, of atorvastatin,
which is stated by the manufacturer to be a possible cause
of liver dysfunction. A patient receiving Caduet, however,
would have to thus also discontinue amlodipine, which is
not in this example desired by the physician. A tablet of
the invention in which atorvastatin and amlodipine were
segregated in different outer active segments, separated by
a middle segment of adequate dimensions, would be a clear
advance over the current Caduet formulation, because such a
tablet would allow a patient to promptly continue ingesting
amlodipine while stopping ingestion of atorvastatin,
without having to go to a pharmacy and fill a new
prescription for a tablet containing only amlodipine as the
active ingredient, while having previously had the
convenience of having both drugs combined in a single
dosage form. The above embodiment of the invention
represents an improvement over the current Caduet dosage

form.
Another clinical situation in which the invention is
superior to Caduet is one in which a patient receiving
amlodipine 5 mg once daily and atorvastatin 20 mg once
daily is advised by a physician to increase the daily
amlodipine dose to 10 mg once daily. A patient in
possession of adequate tablets of the invention, with the
active drugs segregated in a three-segment tablet, would be
able to promptly increase the amlodipine dose by taking a
whole "tablet of the invention once daily, plus a tablette
containing 5 mg of amlodipine, produced by breaking a
second whole tablet of the invention.
Another clinical situation in which the invention is
superior to Caduet involves the case in which a physician
wishes a patient to ingest atorvastatin 20 mg each morning
and amlodipine 2.5 mg twice daily. The invention provides
for amlodipine to be separated from atorvastatin and then
broken precisely in half. The invention thus allows the
patient the advantage of one tablet, whereas to accomplish
this currently in the United States would require one 2 0 mg
Lipitor® (atorvastatin) tablet and two Norvasc®
(amlodipine) 2.5 mg tablets.
2. The combination of amlodipine besylate and benazepril
hydrochloride (benazepril) is marketed in the United States
under the brand name of Lotrel®. This product is a capsule
that is routinely ingested whole. An embodiment of the
invention provides a whole tablet containing one outer
segment containing amlodipine as the only active drug and
the other outer segment containing benazepril as the only
outer drug. If desired, either outer layer may be formed

into more than one segment, as in Fig. la. As in example 1
above regarding Caduet, the middle segment is inactive and
may be broken through to create two tablettes, each
comprising a whole amount of each outer active segment plus
approximately half of the amount of the middle inactive
segment. If a patient were to develop a need for double
the dose of one active drug but not the other, the tablet
of the invention could meet that need. Alternatively, if a
patient were to develop a need to ingest only one active
drug, possibly temporarily, due to such conditions as blood
pressure changes or a side effect to one drug but not the
other, the tablet of the invention allows this to be done
without a new dosage form being prescribed.
3. Another use of the invention involves the combination
of amlodipine and chlorthalidone or another diuretic, which
may usefully be combined to treat hypertension. Benefits
of the invention are similar to those described in the
paragraph immediately preceding this paragraph.
4 . Another use of the invention involves the combination
of olmesartan medoxomil (olmesartan, an angiotensin
receptor blocker) and hydrochlorothiazide (HCTZ). This
product is currently marketed in the United States under
the name Benicar/HCT®, with the doses, respectively, of, in
mg: 20/12.5, 40/12.5, and 40/25. A very common starting
dose of a patient will be 20/12.5 once daily. The product
is currently marketed in all strengths as a homogeneous
tablet containing both active drugs. Formulated according
to the current invention, a patient who begins treatment
with the 20/12.5 dose may be increased with the same tablet
to each of the other doses by ingesting one whole 20/12.5
tablet and either a half tablet containing 20 mg of

olmesartan or a half tablet containing 25 mg of HCTZ. This
will provide the physician an opportunity to investigate
the new dose before giving the patient a new prescription.
Other advantages of the invention are similar to those
described above.
5. Another useful combination product that may be
formulated according to the invention involves angiotensin
converting enzyme inhibitors (ACEs) and diuretics such as
HCTZ. Both types of drug not uncommonly have side effects,
so that the invention will be useful to physicians in
dealing with the side effects, as well as with changing
dosing needs to deal with the anti-hypertensive and other
clinical benefits of the drugs.
6. Another product that may benefit from the invention
regarding separating active drugs in separate outer layers
with an inactive middle segment (layer) is a combination
product containing two active drugs, fluoxetine and
olanzapine.
No limitation to the above therapeutic fields or to the
specific examples within their fields is intended for
tablets of the invention, which may be used in any suitable
combination of drugs. No limitation to two-drug
combinations exists, as well. For instance, one outer
active segment of a tablet according to the invention could
contain levodopa and carbidopa, and the other outer active
segment could contain entacapone, a tablet product
containing all three drugs in a homogeneous fashion that is
currently marketed in the United States as Stalevo®. Also,
a tablet per the invention could involve five layered
segments, with, for example, amlodipine in one outer

segment, an inactive segment adjoining it, a middle segment
containing chlorthalidone or HCTZ, and a second inactive
Segment adjoining both it and the other outer segment that
contains benazepril (see Fig. 8). If both inactive
segments were of adequate dimensions to be conveniently
breakable without damaging any of the three active
segments, thus providing significant clinical advantages
due to the adoption of flexible dosing of the different
active segments.
The following list of possible combinations of a plurality
of drugs is exemplary and not limiting. The combinations
referred to may include two or more members of the classes
listed. Drugs listed below, and herein, may for
convenience exclude mention of any salt of a drug; e.g.,
"atorvastatin" is listed even though its marketed form is
atorvastatin calcium.
without limitation, useful combinations may include a
plurality of drugs from within the following six drug
classes.
In addition, tablets of the invention may be created
containing only one of a drug from the following list.
With regards to combination use, two methods of use may
apply to the invention. One of these methods is to place
an individual drug in a granulation and a different
individual drug (or combination of drugs) in a different
granulation, potentially with an inactive granulation
interposed between them; another method is to place a
plurality of drugs in one or more segments.
1. Anti-anginal agents, for example:

A. Calcium antagonists (see list below);
B. Beta-blocker (see list below);
C. Organic nitrate preparation (e.g., isosorbide
mononitrate or dinitrate) .
2. Anti-anginal agent plus an anti-platelet agent, such
as aspirin, clopidogrel, or ticlopidine.
3. Two hypoglycemic agents (see list below).
4. Potassium chloride and any thiazide-type or loop
diuretic (see lists below).
5. Lipid-lowering agent plus: hypoglycemic agent, anti-
platelet agent, anti-anginal agent, and/or
antihypertensive agent (see lists above and below)
Hypoglycemic agents include: thiazolidinediones:
pioglitazone, rosiglitazone; sulfonylureas: glyburide,
glipizide, glimepiride, chlorpropamide;
Biguanides: metformin;
Meglitinides: nateglinide, repaglinide;
Glucosidase inhibitors: acarbose, miglitol.
6. Antihypertensive agents:
Beta-blockers: acebutolol, atenolol, bisoprolol,
celiprolol, metoprolol, mebivolol, carvedilol (a mixed
alpha-beta blocker), nadolol, oxprenolol, penbutolol,
pindolol, propranolol, timolol, betaxolol, carteolol;
Calcium antagonists (calcium-channel blockers): nifedipine,
amlodipine, verapamil, diltiazem, nisoldipine, felodipine,
isradipine, lacidipine, lercanidipine, nicardipine,
manidipine;
Thiazide-type diuretics (with or without potassium-
retaining diuretics such as triamterene, amiloride, or
spironolactone) : hydrochlorothiazide, chlorothiazide,
cyclopenthiazide, polythiazide, bendrofluazide,

hydroflumethiazide, chlorthalidone, indapamide,
methylclothiazide, metolazone;
Angiotensin converting enzyme inhibitors: captopril,
enalapril, lisinopril, ramipril, trandolapril, quinapril,
perindopril, moexipril, benazepril, fosinopril;
Angiotensin receptor blockers: losartan, valsartan,
candesartan, telmisartan, eprosartan, irbesartan;
High-ceiling (loop) diuretics (with or without potassium-
retaining diuretics such as triamterene, amiloride, or
spironolactone): furosemide, torsemide, ethacrynic acid,
bumetamide;
Aldosterone antagonist diuretics: spironolactone,
eplerenone;
Alpha-blockers: doxazosin, terazosin, prazosin, indoramin,
labetolol (a mixed alpha-beta blocker);
Central alpha-agonists: clonidine, methyldopa;
Imidazoline: moxonidine;
Direct vasodilators: hydralazine, minoxidil;
Adrenergic neuronal blocker: guanethidine.

Lipid-lowering agents include:
Statins: lovastatin, simvastatin, pravastatin,
rosuvastatin, atorvastatin, fluvastatin;
Fibrates; clofibrate, bezafibrate, fenofibrate,
gemfibrozil, ciprofibrate;
Others: ezetimide, niacin, acipimox.
The combinations of drugs disclosed herein are for
illustrative purposes and are not intended to limit the
scope of the invention.
Regarding the important usage of the tablets and tablettes
of the invention, that involving division of a tablet into

tablettes containing similar active segments, most drugs
that may undergo dosage adjustment will be preferred if
they may be divided in an optimally precise manner.
Examples of drugs that will especially benefit from the
advances of the invention in this manner include narrow
therapeutic index drugs such as warfarin, digoxin, L-
thyroxine; vasoactive drugs such as amlodipine;
hypoglycemic agents such as rosiglitazone and glipizide;
and anxiolytics drugs such as alprazolam. These are
however but a small fraction of the great mass of drugs
that will benefit from the various embodiments and
procedures of the invention.
There are numerous methods of use of the dosage forms of
the invention, including its tablets and tablettes.
Persons skilled in the medical and pharmaceutical arts will
recognize the many advantages that the various embodiments
of the invention allow over current products. Some
examples of benefits of the inventions involving tablets
containing exactly one similar active segment described
immediately below.
1. Warfarin is an anticoagulant marketed in the U.S. under
the brand name Coumadin®, which is a scored tablet.
Research has shown that patients do not break warfarin 5 mg
tablets into equal 2.5 mg segments. The invention teaches
different types of tablets that allow warfarin tablets of
any common human dose to be broken into precise halves, and
potentially precise thirds, quarters, etc. Thus a patient
may utilize warfarin half-tablets produced as per the
invention with similar confidence as in the whole tablet.
Because warfarin doses are frequently broken, many clinical
scenarios exist in which the invention will benefit

patients.
2. Norvasc (amlodipine besylate or amlodipine herein) is
marketed as unscored 2.5, 5, and 10 mg tablets in the U.S.
These tablets are of irregular shape and are difficult to
break. The FDA-approved dosage range is from 2.5 to 10 mg
ingested orally daily. The invention allows improved
functionality of amlodipine. For example, under the
invention, a patient receiving 5 mg daily who a physician
wishes to increase to 7.5 mg daily may simply utilize a
tablet of the invention that comprises two separate 2.5 mg
segments to increase the dose to precisely 7.5 mg, such as
by ingesting one whole 5 mg tablet and one 2.5 mg tablette
created by breaking a 5 mg tablet into two tablettes each
containing 2.5 mg of amlodipine. Convenience and cost
savings are clear. Similarly, a patient receiving a 10 mg
dose of Norvasc who is advised to reduce the dose to 5 mg
daily must currently purchase a new prescription for 5 mg
Norvasc tablets. The invention provides the ability to
provide a 10 mg tablet that may be broke into two
tablettes, each containing precisely 5 mg of
t
The invention may therefore enable greater flexibility of
treating patients, and provide cost savings as well. A
further benefit of the invention is that various
embodiments allow fully accurate separation of a tablet
into a tablette comprising one-fourth of the dose of the
active ingredient as is found in the whole tablet. This
may for example be done for amlodipine by providing four
active segments all containing 2.5 mg of amlodipine and all
contiguous with the same side of an inactive outer segment
(see embodiment #1; and see Fig. 6a modified to have four
and not two active segments) . Thus, a 10 mg amlodipine
tablet of the invention may be utilized to provide a 7.5 mg

dose; or, it may be utilized to provide four 2.5 mg doses.
A further benefit of the invention may relate to pediatric
or geriatric doses, which may not be produced in
appropriate dose strengths. In the case of amlodipine, a
1.25 mg daily dose may be useful in either small children
with hypertension, or in frail elderly patients with angina
or hypertension, who may have hepatic dysfunction. Even
though the United States Food and Drug Administration (FDA)
has not approved a 1.25 mg dose, precise divisibility of
the approved 2.5 mg dose would allow a 1.25 mg daily dose.
In addition, precise divisibility of the approved 2.5 mg
dose will allow accurate dosing of 3.75 mg daily.
Another use of the invention is to for the first time
enable a method of cost savings to insurers and patients.
The invention allows this because many drugs, such as
Norvasc and Coumadin, have pricing that differs little (if
at all) between different doses. Because tablet splitting
is imprecise for most scored tablets, the practice of
mandatory splitting has been met with disapproval by most
physician and pharmacist organizations. The invention
enables tablet splitting due to provide accurate dosing
when a tablet (or some tablettes, as in Fig. lb) of the
invention are broken as described herein. Substantial
benefits are foreseen from this innovation. In addition,
the ability to separate one active drug from another in a
combination product has cost saving advantages, as well.
It is recognized that related inventions may be within the
spirit of the disclosures herein. Also no omission in the
current application is intended to limit the inventors to
the current claims or disclosures. While certain preferred

and alternative embodiments of the invention have been set
forth for purposes of disclosing the invention,
modifications to the disclosed embodiments may occur to
those who are skilled in the art.

WE CLAIM:
1. An immediate release compressed pharmaceutical tablet comprising
two or more active segments and at least one inactive segment, said at
least one inactive segment being between said active segments and
serving as a breaking region to allow breaking only through said at least
one inactive segment, said tablet further comprising a top and a bottom
and having a height that exceeds the width of said tablet, said height
being measured vertically from the top to the bottom of said tablet while
it is in the tablet die in which it is fully compressed, after said
compression is completed; and said width being measured as the
greatest horizontal dimension of the tablet at a location halfway between
said top and said bottom of said tablet, except that when the horizontal
cross section of said tablet is substantially rectangular, the width is
defined by locating the two shorter sides of the perimeter of said
horizontal cross-section, and measuring the length of a line that is at
right angle to said shorter sides.
2. An immediate release compressed pharmaceutical tablet as claimed in
claim 1, the active segments of which contain the same drug or drugs.
3. An immediate release compressed pharmaceutical tablet as claimed in
claim 2 wherein said tablet contains two or more active segments that
have different concentrations of a drug or drugs, relative to inactive
excipients in each segment, on a weight to weight basis.
4. An immediate release compressed pharmaceutical tablet as claimed in
claim 2 which comprises three segments, said three segments being a

first inactive segment being an inner interposed segment between a
second segment and a third segment, said second segment being an
upper segment, and said third segment being a lower segment, said
second and third segments being substantially identical.
5. An immediate release compressed pharmaceutical tablet that contains
a core structure consisting of the tablet as claimed in claim 4.
6. An immediate release compressed pharmaceutical tablet as claimed in
claim 1 that comprises two vertically disposed segments that each
contain a pharmacologically effective quantity of a drug or drugs, in
which said drug or drugs in each vertically disposed segment are
different.
7.An immediate release compressed pharmaceutical tablet as claimed in
claim 6 that consists of a first segment that is an inner, interposed
segment between a second upper segment and a third lower segment,
said second and third segments containing a different drug or drugs.
8.An immediate release compressed pharmaceutical tablet as claimed in
claim 1 in which all vertically disposed segments are not substantially
identical.
9.An immediate release compressed pharmaceutical tablet as claimed in
claim 1 in which a score is placed in a segment which is not a top or
bottom segment.

10.An immediate release compressed pharmaceutical tablet as claimed
in claim 1 in which printed marks or other indicia are applied to said
tablet in a segment other than the top or bottom segment and that locate
a desired breaking region of said tablet.
11.An immediate release compressed pharmaceutical tablet as claimed
in claim 1 in which a score is placed substantially horizontally in a side
of the tablet.
12. An immediate release compressed pharmaceutical tablet as claimed
in claim 1 in which a printed mark or other indicia are placed
substantially horizontally on a side of said tablet to locate a place on a
side of said tablet that is a desired breaking region.
13.An immediate release compressed pharmaceutical tablet as claimed
in claim 4 in which said second and third segments occupy no more than
20% of the height of said tablet.
14.An immediate release compressed pharmaceutical tablet as claimed
in claim 13 in which said second and third segments occupy no more
than 10% of the height of said tablet.
15. A pharmaceutical tablet as claimed in claim 1 in which said drug or
drugs is or are pharmacologically effective in the treatment of
cardiovascular conditions, psychiatric conditions, diabetes, thyroid
disorders, pain or thrombotic disorders.


An immediate release compressed pharmaceutical tablet that has two or
more segments and a top and a bottom and has a height that exceeds the
width of the tablet. The height is measured vertically from the top to the
bottom of the tablet while it is in the tablet die in which it is fully
compressed, after compression has been completed. The width is measured
as the greatest horizontal dimension of the tablet at a location halfway
between the top and the bottom of the tablet, except that when the
horizontal cross-section of the tablet is substantially rectangular, the width is
defined by locating the two shorter sides of the perimeter of the horizontal
cross-section, and measuring the length of a line that is at right angle to the
shorter sides.

Documents:

03323-kolnp-2006-abstract.pdf

03323-kolnp-2006-claims.pdf

03323-kolnp-2006-correspondence others-1.1.pdf

03323-kolnp-2006-correspondence others.pdf

03323-kolnp-2006-description(complete).pdf

03323-kolnp-2006-drawings.pdf

03323-kolnp-2006-form-1.pdf

03323-kolnp-2006-form-2.pdf

03323-kolnp-2006-form-3.pdf

03323-kolnp-2006-form-5.pdf

03323-kolnp-2006-international publication.pdf

03323-kolnp-2006-pct others.pdf

3323-KOLNP-2006-(23-05-2012)-CORRESPONDENCE.pdf

3323-KOLNP-2006-ABSTRACT 1.1.pdf

3323-KOLNP-2006-AMANDED CLAIMS-1.1.pdf

3323-KOLNP-2006-ASSIGNMENT 1.1.pdf

3323-KOLNP-2006-ASSIGNMENT 1.3.pdf

3323-KOLNP-2006-ASSIGNMENT.pdf

3323-KOLNP-2006-CLAIMS.pdf

3323-KOLNP-2006-CORRESPONDENCE 1.1.pdf

3323-KOLNP-2006-CORRESPONDENCE 1.2.pdf

3323-kolnp-2006-correspondence 1.3.pdf

3323-KOLNP-2006-CORRESPONDENCE 1.4.pdf

3323-KOLNP-2006-CORRESPONDENCE-1.2.pdf

3323-KOLNP-2006-DESCRIPTION (COMPLETE) 1.1.pdf

3323-KOLNP-2006-DESCRIPTION (COMPLETE)-1.2.pdf

3323-KOLNP-2006-DRAWINGS 1.1.pdf

3323-KOLNP-2006-DRAWINGS-1.2.pdf

3323-KOLNP-2006-EXAMINATION REPORT REPLY RECIEVED.pdf

3323-KOLNP-2006-EXAMINATION REPORT.pdf

3323-KOLNP-2006-FORM 1 1.1.pdf

3323-KOLNP-2006-FORM 1 1.2.pdf

3323-KOLNP-2006-FORM 1-1.3.pdf

3323-KOLNP-2006-FORM 18 1.1.pdf

3323-kolnp-2006-form 18.pdf

3323-KOLNP-2006-FORM 2 1.1.pdf

3323-KOLNP-2006-FORM 2 1.2.pdf

3323-KOLNP-2006-FORM 2-1.3.pdf

3323-KOLNP-2006-FORM 26.pdf

3323-KOLNP-2006-FORM 3 1.1.pdf

3323-KOLNP-2006-FORM 3 1.2.pdf

3323-KOLNP-2006-FORM 3.pdf

3323-KOLNP-2006-FORM 5 1.1.pdf

3323-KOLNP-2006-FORM 5.pdf

3323-KOLNP-2006-FORM 6 1.1.pdf

3323-KOLNP-2006-FORM 6.pdf

3323-KOLNP-2006-GPA.pdf

3323-KOLNP-2006-GRANTED-ABSTRACT.pdf

3323-KOLNP-2006-GRANTED-CLAIMS.pdf

3323-KOLNP-2006-GRANTED-DESCRIPTION (COMPLETE).pdf

3323-KOLNP-2006-GRANTED-DRAWINGS.pdf

3323-KOLNP-2006-GRANTED-FORM 1.pdf

3323-KOLNP-2006-GRANTED-FORM 2.pdf

3323-KOLNP-2006-GRANTED-SPECIFICATION.pdf

3323-KOLNP-2006-MISCLLENIOUS.pdf

3323-KOLNP-2006-OTHERS 1.3.pdf

3323-KOLNP-2006-OTHERS-1.1.pdf

3323-KOLNP-2006-OTHERS.pdf

3323-kolnp-2006-pa 1.1.pdf

3323-KOLNP-2006-PA.pdf

3323-KOLNP-2006-PETITION UNDER RULE 137-1.1.pdf

3323-kolnp-2006-petition under section 8(1) read with rule 12.pdf

3323-KOLNP-2006-REPLY TO EXAMINATION REPORT 1.1.pdf


Patent Number 253493
Indian Patent Application Number 3323/KOLNP/2006
PG Journal Number 30/2012
Publication Date 27-Jul-2012
Grant Date 25-Jul-2012
Date of Filing 13-Nov-2006
Name of Patentee ACCU-BREAK TECHNOLOGIES INC.
Applicant Address 1000 SOUTH PINE ISLAND RD.,SUITE 430, PLANTATION, FLORIDA 33324,USA
Inventors:
# Inventor's Name Inventor's Address
1 SOLOMON, LAWRENCE 7810 ALTON VILLA CT.,TORONTO, ONTARIO M5R 3B7, BOCA RATON, FL 33433
2 KAPLAN, ALLAN,S. 7011 Mallorca Cresent, Boca Raton, FL 33433
PCT International Classification Number A01N25/34; A61K6/00
PCT International Application Number PCT/US2005/018633
PCT International Filing date 2005-05-23
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 60/573,134 2004-05-21 U.S.A.
2 60/573,042 2004-05-21 U.S.A.