U.S. patent application number 11/909408 was filed with the patent office on 2009-07-16 for tablet.
This patent application is currently assigned to TAKEDA PHARMACEUTICAL COMPANY LIMITED. Invention is credited to Inhyok Cha, Sudheer A. Grandhi, Catherine M. Livet, Mohammed Sammour, Juan Carlos Zuniga.
Application Number | 20090181082 11/909408 |
Document ID | / |
Family ID | 37073371 |
Filed Date | 2009-07-16 |
United States Patent
Application |
20090181082 |
Kind Code |
A1 |
Zuniga; Juan Carlos ; et
al. |
July 16, 2009 |
TABLET
Abstract
The present invention can retain the volume of a tablet large
without increasing the thickness of the tablet or the like
dimension and prevents a plurality of tablets from sticking to each
other even if they are subjected to a film-coating or the like
treatment, so as to improve the yield. The tablet is a tablet (1)
longer in one direction when seen in plan. The tablet (1) has side
edges (6) each of which extends in a longitudinal direction and is
formed in the shape of a curve projecting outwardly in plan view.
The curve has a radius of curvature (R1) set to at least 1.5 times
a length (L) of the tablet. This makes a projected area of the
tablet (1) in plan view at least 97% with respect to a projected
area of a standard elliptical tablet having opposite end portions
each of which is formed by a semi-circle having a diameter of a
width (W) of the tablet.
Inventors: |
Zuniga; Juan Carlos;
(Montreal, CA) ; Grandhi; Sudheer A.; (Mamaroneck,
NY) ; Sammour; Mohammed; (Montreal, CA) ;
Livet; Catherine M.; (Montreal, CA) ; Cha;
Inhyok; (Yardley, PA) |
Correspondence
Address: |
RANKIN, HILL & CLARK LLP
38210 Glenn Avenue
WILLOUGHBY
OH
44094-7808
US
|
Assignee: |
TAKEDA PHARMACEUTICAL COMPANY
LIMITED
Osaka-shi, Osaka
JP
|
Family ID: |
37073371 |
Appl. No.: |
11/909408 |
Filed: |
March 30, 2006 |
PCT Filed: |
March 30, 2006 |
PCT NO: |
PCT/JP2006/306645 |
371 Date: |
September 21, 2007 |
Current U.S.
Class: |
424/464 |
Current CPC
Class: |
A61P 3/10 20180101; A61K
9/2072 20130101 |
Class at
Publication: |
424/464 |
International
Class: |
A61K 9/20 20060101
A61K009/20 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 31, 2005 |
JP |
2005-102578 |
Claims
1. A tablet being longer in one direction when seen in plan and
having side edges each of which extends along a longitudinal
direction and is formed in the shape of a curve projecting
outwardly, wherein the tablet has a projected area in plan view of
at least 97% with respect to a projected area of a standard
elliptical tablet having opposite end portions each of which is
formed by a semi-circle having a diameter of a width of the
tablet.
2. The tablet as set forth in claim 1, having the whole periphery
formed by curves projecting outwardly when seen in plan.
3. The tablet as set forth in claim 3, having a longitudinal end
portion formed by an end arc of a radius of curvature, the end arc
having opposite ends smoothly connected to the sides edges
extending along the longitudinal direction.
4. A tablet being longer in one direction when seen in plan and
having side edges each of which extends along a longitudinal
direction and is formed in the shape of a curve projecting
outwardly, wherein the side edge has a radius of curvature at least
1.5 times a length of the tablet.
5. The tablet as set forth in claim 4, which has a projected area
in plan view of at least 97% with respect to a projected area of a
standard elliptical tablet having opposite end portions each of
which is formed by a semi-circle having a diameter of a width of
the tablet.
6. The tablet as set forth in claim 4, wherein the side edge has
the radius of curvature not more than 6 times the tablet
length.
7. The tablet as set forth in claim 4, wherein the whole periphery
of the tablet is formed by curves projecting outwardly.
8. The tablet as set forth in claim 7, having a longitudinal end
portion formed by an end arc of a radius of curvature, the end arc
having opposite ends smoothly connected to the sides edges
extending along the longitudinal direction.
9. The tablet as set forth in claim 5, wherein the side edge has
the radius of curvature not more than 6 times the tablet
length.
10. The tablet as set forth in claim 5, wherein the whole periphery
of the tablet is formed by curves projecting outwardly.
11. The tablet as set forth in claim 6, wherein the whole periphery
of the tablet is formed by curves projecting outwardly.
12. The tablet as set forth in claim 9, wherein the whole periphery
of the tablet is formed by curves projecting outwardly.
Description
1. TECHNICAL FIELD
[0001] The present invention relates to a tablet which is longer in
one direction when seen in plan and more particularly to a tablet
whose volume can be retained large without increasing its thickness
or the like dimension and also whose yield can be improved by
preventing them from sticking to each other even if they are
subjected to a film-coating or the like treatment.
BACKGROUND ART
[0002] There are known various shapes of tablets. One of them is a
tablet which is longer in one direction when seen in plan (for
example, see Patent Literature 1). Concrete examples of them are a
substantially rectangular tablet (51) having smooth corners when
seen in plan as shown in FIG. 4(a), a standard elliptical tablet
(53) having its both ends (52) formed by semi-circles each of which
has a diameter of a tablet width (W) when seen in plan as shown in
FIG. 4(b) and a substantially oval tablet (55) having its side
edges (54) each formed in the shape of a smooth arc (hereafter
referred to as an `oval tablet`).
[0003] Among them, the oval tablet (55) has a side edge (54) formed
by an arc having a radius (R1), for example, about 1.5 times a
tablet length (L), to which an end arc having a further smaller
radius (R2) is connected smoothly so as to form an end portion
(52). This oval tablet (55) has only a projected area of about 80%
when compared with a rectangular tablet (56) having a width (W) and
a length (L) (see FIG. 4(c)). So in order to keep the volume of
this oval tablet large, it is necessary, for example, to increase
the thickness of the tablet when compared with the standard
elliptical tablet (53). However, there was a problem that if the
thickness of the tablet is increased, the tablet could hardly be
swallowed when it was dosed.
[0004] On the other hand, as for the substantially rectangular
tablet (51) and the elliptical tablet (53) when seen in plan, the
projected area is large in plan view. For example, in the case of
the standard elliptical tablet (53), usually, the projected area is
about 86% to 90% with respect to the rectangular tablet (56) (see
FIG. 4(b)) having the width (W) and the length (L), although it may
be different depending on the ratio of the width to the length.
Further, as to the substantially rectangular tablet (51) when seen
in plan, apparently, the ratio of its projected area is much
higher. Thus as for these tablets, it is possible to easily retain
the volume large without increasing the thickness of the tablet and
the like dimension.
[0005] However, each of these substantially rectangular tablet (51)
and the elliptical tablet (53) has a long linear portion at a side
edge (54) in plan view, so that when it is subjected to the
film-coating treatment, the long linear portion of this side edge
(54) sticks to the other tablet through a coating agent to produce
a so-called "twinning" defective product (hereafter referred to as
"twin tablet"), which entails a problem of being not easy to
improve the yield. Here, the twinning defective product also
includes a defective product comprising at least three tablets
mutually stuck.
[0006] Patent Literature 1: Utility Model Application Laid-Open No.
5-37924
DISCLOSURE OF THE INVENTION
The Problem the Invention Intends to Solve
[0007] The present invention has a technical object to solve the
above-mentioned problems and provide a tablet which keeps its
volume large without increasing its thickness or the like dimension
and to enhance the yield by preventing a plurality of tablets from
sticking to each other even if they are subjected to the
film-coating or the like treatment.
Means for Solving the Problem
[0008] The present invention is constructed as follows so as to
accomplish the above-mentioned object, for example, if it is
explained based on FIGS. 1 to 3 which show embodiments of the
present invention.
[0009] More specifically, a first invention 1 concerns a tablet
longer in one direction, when seen in plan, which has a side edge 6
along a longitudinal direction formed by a curve projecting
outwards when seen in plan view and has a projected area in plan
view of at least 97% with respect to that of a standard elliptical
tablet having both ends each of which is formed by a semi-circle
having a diameter of a tablet width (W).
[0010] Further, a second invention 2 relates to a tablet longer in
one direction when seen in plan and having a side edge 6 along the
longitudinal direction, formed by a curve projecting outwards when
seen in plan view. The side edge 6 has a radius of curvature (R1)
at least 1.5 times a tablet length (L).
[0011] Hereafter, in the specification, the tablet of the first
invention 1 and the tablet of the second invention 2 may be
sometimes briefly referred to only as "the tablet of the present
invention".
[0012] Here, the tablet may have ends formed mostly by straight
lines like the substantial rectangle having round corners when seen
in plan view or formed by one or plural arcs in combination like
the substantial ellipse when seen in plan.
[0013] The aforesaid ratio of the projected area (hereafter
referred to only as "projected area ratio") of this tablet when
seen in plan view to the projected area of the standard elliptical
tablet differs depending on not only the shape of the tablet end
portion, but also the ratio of the tablet width to the tablet
length and the radius of curvature of the side edge. As the radius
of curvature of the side edge is larger, the projected area ratio
can become larger.
[0014] As for the tablet of the present invention, its length is
preferably set to about 1.5 to 2 times the tablet width from the
aspect of the readiness and quantity of dosing. In this case, if
the radius of curvature of the side edge is at least 1.5 times the
tablet length, the projected area ratio can be easily set to at
least 97%. So this is preferable. If it is at least two times the
tablet length, the projected area ratio can become larger more
assuredly. This is more preferable.
[0015] However, should the radius of curvature be excessively
large, the arc of the side edge comes to readily butt against the
side edge of the adjacent tablet over a long range when it is
subjected to the film-coating treatment. As a result, there is a
likelihood of twinning. Therefore, the radius of curvature is
preferably set to not more than 6 times, preferably not more than
4.5 times, more preferably not more than 4 times the tablet
length.
[0016] As regards a periphery of the tablet when seen in plan view,
for example, the opposite end portions may be partly linear. But if
whole the periphery is formed by curves projecting outwards in plan
view, it is more preferable because there is no likelihood that the
tablets stick to each other at any portion when it is subjected to
the film-coating treatment.
[0017] In this case, the longitudinal ends of the tablet may be
formed by large and small arcs in combination to which side edges
extending along the longitudinal direction may be connected
smoothly. However, if each of the end portions of this tablet is
formed by an end arc having a single radius of curvature in plan
view, both ends of which end arc are smoothly connected to the side
edges along the longitudinal direction, the shape of the tablet is
so simplified that the working becomes easy and besides the
tablet-making pressure is readily applied to the tablet uniformly.
Thus this is more preferable. Further, although the end arcs
advantageously have their both ends connected to the side edges in
contact relationship, it suffices if they are substantially
smoothly connected thereto. Therefore, they may be connected
together with a slight crossing angle.
[0018] The tablet of the present invention is suitably applied to
the pharmaceutical medicine including pharmaceutical active
components to be dosed in a large quantity or a plurality of
pharmaceutical active components.
[0019] Here, listed as the pharmaceutical active components to be
dosed in a large quantity, are, for example, metoformin or its
salts (for example, hydrochloride), cefotiam hexetil hydrochloride,
azithromycin hydrate, valaciclovir hydrochloride, and
gabapentin.
[0020] Besides, listed as the plurality of pharmaceutical active
components are, for example, a plurality of therapeutic agents for
diabetes which provide mutually different effects and functions.
Concretely, a combination of metoformin or its salts (for example,
hydrochloride) with pioglytazon or its salts (for example,
hydrochloride) is listed.
[0021] The tablet of the present invention weights at least 150 mg,
preferably at least 300 mg, more preferably at least 600 mg. The
upper limit is within a range where the tablet can be swallowed
when it is dosed. Particularly, in the case where the tablet of the
present invention weights at least 300 mg, the effect of the
present invention, to be mentioned later, that the volume of the
tablet can be kept large without increasing the thickness of the
tablet or the like dimension will be exerted extraordinarily.
[0022] The tablet of the present invention is preferably a
film-coated tablet having a film-coating layer from the view point
of being easy to dose and well resistant to sun light, being able
to make a good release control and having a sufficient hardness for
pharmaceutical.
[0023] Here, the film-coating layer is generally 10 to 200 .mu.m in
thickness. This film-coating layer preferably contains a coating
substrate (for example, hydroxypropylmethyl cellulose,
hydroxypropyl cellulose, cellulose acetate, ethyl cellulose,
methacrylic acid copolymer LD); in addition, a sunscreen agent such
as titanium oxide, talc, 3,2 iron oxide; and a plasticizer such as
polyethylene glycol, propylene glycol, polysolvate, triethyl
citrate, triacetyne.
[0024] In the case where the tablet of the present invention is a
film-coated tablet, the effect of the present invention
[possibility of preventing a plurality of tablets from sticking to
each other] to be mentioned later is extraordinarily exerted.
EFFECT OF THE INVENTION
[0025] Since the present invention is constituted and functions as
mentioned above, it offers the following effects.
[0026] The first invention has a projected area in plan view set to
at least 97% with respect to the projected area of the standard
elliptical tablet. Further, the second invention has a projected
area ratio increased by setting the radius of curvature of the side
edge to at least 1.5 times the tablet length to result in being
able to keep the volume large without augmenting the thickness of
the tablet and the like dimension.
[0027] Having a side edge in the shape of a curve outwardly
projecting, the tablet does not butt against the adjacent tablet
over a long range. Accordingly, even if it is subjected to the
film-coating or the like treatment, it is possible to prevent a
plurality of tablets from sticking to each other with the result of
being able to easily improve the yield
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIG. 1 is a partly broken perspective view of a tablet
showing an embodiment of the present invention;
[0029] FIG. 2 is a top view, in cross section, of the tablet
according to the embodiment of the present invention;
[0030] FIG. 3 is a Table of Comparison of Dimension in which the
tablet of the embodiment according to the present invention is
compared with that of the prior art in dimension;
[0031] FIG. 4 shows conventional tablets. FIG. 4(a) is a top view,
in cross section, of a substantially rectangular tablet having
smooth corners, FIG. 4(b) is a top view, in cross section, of a
standard elliptical tablet when seen in plan view, and FIG. 4(c) is
a top view, in cross section, of a substantially oval tablet.
EXPLANATION OF NUMERALS
[0032] 1 . . . tablet [0033] 6 . . . side edge [0034] 7 . . . end
portion [0035] 8 . . . end arc [0036] L . . . length of the tablet
[0037] R1 . . . radius of curvature of the side edge (6) [0038] R2
. . . radius of curvature of the end arc (8) [0039] W . . . width
of the tablet
MOST PREFERRED EMBODIMENT OF THE INVENTION
[0040] Hereafter, an explanation is given for the embodiments of
the present invention based on the drawings.
[0041] FIGS. 1 and 2 show embodiments of the present invention.
FIG. 1 is a partly broken perspective view and FIG. 2 is a top
view, in cross section of a tablet. As shown in FIG. 1, a tablet 1
has a main body 2 a peripheral side surface 3 of which is formed
vertical. The main body 2 is formed at its upper and lower surfaces
with projections 4 each of which smoothly protrudes in the shape of
an elliptical semi-sphere. A film-coating 5 is applied to the
surfaces of this tablet 1. As for the components of this
film-coating 5 and the way to carry out the coating treatment, for
example, it is possible to adopt the materials and ways used for
the general tablets and therefore they are not limited to specific
ones. Besides, the components of the tablet 1 itself need not be
limited to specific ones. Additionally, the tablet 1 of the present
invention may have the peripheral side surface 3 tapered.
[0042] As shown in FIG. 2, the tablet 1 is formed in the shape of a
substantial ellipse longer in one direction and has side edges 6
extending along a longitudinal direction, each of which is formed
by a curve projecting outwardly in plan view. A radius of curvature
(R1) of this curve is set to at least 1.5 times, preferably at
least 2 times, and more preferably at least 2.5 times a length (L)
of the tablet.
[0043] The tablet 1 has end portions 7 each of which is formed by
an end arc 8 projecting outwards when seen in in plan. The end arc
8 has a radius of curvature (R2) whose opposite ends are smoothly
connected to the side edges 6, respectively. The radius of
curvature (R2) of the end arc 8 is smaller than half a width (W) of
the tablet. When the end arc 8 is brought into contact with the
side edges 6, the radius of curvature is calculated from the tablet
width (W), the tablet length (L) and the radius of curvature (R1)
of the side edge 6. However, it suffices if the end arc 8 is
substantially smoothly connected to the side edges 6 and therefore
the radius of curvature (R2) may be slightly larger than the
calculated value.
[0044] The side edge 6 has the radius of curvature (R1) so set that
the projected area of the tablet in plan view comes to be at least
86% with respect to the rectangle 9 having the width (W) and the
length (L). Further, this projected area is set to at least 97%
with respect to the projected area of the standard elliptical
tablet of the same width (W) and the same length (L) having
opposite end portions each of which is formed by a semi-circle of
the tablet width (W) as a diameter.
EXAMPLES
[0045] Hereafter, we will explain the present invention in more
detail while listing Examples, Comparison Examples and Test
Examples. But the present invention is not limited to those
Examples.
[0046] In the below-mentioned Examples and Comparison Examples, the
agents which satisfy The Japanese Pharmacopoeia Fourteenth Edition
or the Japanese Pharmaceutical Excipients 2003 were used for
various sorts of additives such as magnesium stearate.
Examples 1 to 7 and Comparison Examples 1 to 5
[0047] The length (L), the width (W) of the tablet shown in FIG. 2
are set to various dimensions as well as the radius of curvature
(R1) of the side edge 6 and the radius of curvature (R2) of the end
arc 8. Then measurements were made for the projected areas of the
respective tablets 1 when seen in plan (Examples 1 to 7). The
results of the measurement were compared with those of the
conventional standard elliptical tablets (Comparison Examples 1 to
3) and oval tablets (Comparison Examples 4 and 5) and were
indicated in Table of Comparison of Dimension in FIG. 3.
[0048] As indicated in Table of Comparison of Dimension in FIG. 3,
each of the tablets of Examples 1 to 7 has a large projected area
ratio of at least 97% with respect to the standard elliptical
tablet and therefore could retain its volume large.
[0049] On the other hand, each of the tablets (oval tablets) of
Comparison Examples 4 and 5 has a narrow projected area in plan
view and as a result could not keep its volume large.
[0050] Hereafter, we will recite how to produce the tablets of
Examples 4, 6 and 7 as well as those of Comparison Examples 1 to
3.
Example 4
[0051] 57800 g of metoformin hydrochloride, 1147 g of pioglytazon
hydrochloride and 2052 g of microcrystalline cellulose were entered
into a flow granulating and drying machine (manufactured by POWREX
CORPORTION, Model WSG-60) and were granulated while spraying 18700
g of purified water containing 3740 g of polyvinylpyrrolidone to
have obtained an intermediate granule through a drying step. The
same operation was repeated twice and obtained a granule.
[0052] 123800 g of the obtained granule was mixed with 8320 g of
microcrystalline cellulose, 6587 g of croscarmellose sodium and 429
g of magnesium stearate.
[0053] The obtained powder granule was made into tablets by using a
tablet-making machine (manufactured by KIKUSUI SEISAKUSHO LTD.,
AQUA 0836, 18.5 mm.times.10 mm in dimension of tablet, compression
pressure of 27 kN/punch, shape of rod; substantially oval, ratio of
radius of curvature of a side edge with respect to the length of a
tablet: 2.53) to have obtained tablets each of which weighs 1220
mg.
[0054] 122600 g of the obtained tablets were thrown into a
film-coating device (manufactured by POWREX CORPORTION, DRS-1200DS)
to coat them by spraying 35172 g of purified water containing 2227
g of hydroxypropylmethyl cellulose, 430 g of polyethylene glycol
6000, 430 g of titanium oxide and 430 g of talc dispersed, at an
inlet temperature of 80 degrees C. in an amount of 200 g/min. Then
film-coated tablets, each of which weights 1255 mg, were
obtained.
Example 6
[0055] 20000 g of pioglytazon hydrochloride and 4998 g of
microcrystalline cellulose were entered into a mixing machine
(manufactured by POWREX CORPORTION, vertical granulator) and were
mixed while agitating them. The obtained mixture was crushed by a
jet-mill crusher (manufactured by NPK Company, Model 100SP) to have
obtained crushed mixture of pioglytazon hydrochloride and
microcrystalline cellulose.
[0056] 85000 g of metoformin hydrochloride, 2107 g of the crushed
mixture of pioglytazon hydrochloride and microcrystalline
cellulose, and 2637 g of microcrystalline cellulose were entered
into a flow granulating and drying machine (manufactured by POWREX
CORPORTION, Model STRE-5M) and were granulated while spraying 27500
g of purified water containing 5500 g of polyvinylpyrrolidone to
have obtained an intermediate granule through a drying step. The
same operation was repeated three times and obtained a granule.
[0057] The obtained granule was mixed with 19200 g of
microcrystalline cellulose, 15200 g of croscarmellose sodium and
990 g of magnesium stearate.
[0058] The obtained powder granule was made into tablets by using a
tablet-making machine (manufactured by KIKUSUI SEISAKUSHO LTD.,
Correct D55, 17.5 mm.times.9.5 mm in dimension of tablet,
compression pressure of 27 kN/punch, shape of rod; substantially
oval, ratio of radius of curvature of a side edge with respect to
the length of a tablet: 2.63) to have obtained tablets each of
which weights 1070 mg.
[0059] The obtained tablets were thrown into a film-coating device
(manufactured by POWREX CORPORTION, DRS-1600) to coat them by
spraying 90000 g of purified water containing 5697 g of
hydroxypropylmethyl cellulose, 1100 g of polyethylene glycol 6000,
1100 g of titanium oxide and 1100 g of talc dispersed, at an inlet
temperature of 80 degrees C. in an amount of 200 g/min. Then
film-coated tablets, each of which weights 1100 mg, were
obtained.
Example 7
[0060] 20000 g of pioglytazon hydrochloride and 4998 g of
microcrystalline cellulose were entered into the mixing machine
(manufactured by POWREX CORPORTION, vertical granulator) and were
mixed while agitating them. The obtained mixture was crushed by a
jet-mill crusher (manufactured by NPK Company, Model 100SP) to have
obtained crushed mixture of pioglytazon hydrochloride and
microcrystalline cellulose.
[0061] 85000 g of metoformin hydrochloride, 3582 g of the crushed
mixture pioglytazon hydrochloride and microcrystalline cellulose,
and 2409 g of microcrystalline cellulose were entered into a flow
granulating and drying machine (manufactured by POWREX CORPORTION,
MODEL STRE-5M) and were granulated while spraying 28050 g of
purified water containing 5610 g of polyvinylpyrrolidone to have
obtained an intermediate granule through a drying step. The same
operation was repeated three times and obtained a granule.
[0062] The obtained granule was mixed with 19380 g of
microcrystalline cellulose, 15390 g of croscarmellose sodium and
1020 g of magnesium stearate.
[0063] The obtained powder mixture was made into tablets by using a
tablet-making machine (manufactured by KIKUSUI SEISAKUSHO LTD.,
Correct, D55, 13.5 mm.times.8.5 mm in dimension of tablet,
compression pressure of 14 kN/punch, shape of rod; substantially
oval, ratio of radius of curvature of a side edge with respect to
the length of a tablet: 3.41) to have obtained tablets each of
which weighs 638 mg.
[0064] The obtained tablets were thrown into a film-coating device
(manufactured by POWREX CORPORTION, DRS-1600) to coat them by
spraying 96900 g of purified water containing 6139 g of
hydroxypropylmethyl cellulose, 1183 g of polyethylene glycol 6000,
1183 g of titanium oxide and 1183 g of talc dispersed, at an inlet
temperature of 80 degrees C. in an amount of 200 g/min. Then
film-coated tablets, each of which weights 657 mg, were
obtained.
Comparison Example 1
[0065] The powder mixture obtained in Example 4 was made into
tablets by using a tablet-making machine (manufactured by KIKUSUI
SEISAKUSHO LTD., AQUA 0836, 18.5 mm.times.10 mm in dimension of
tablet, compression pressure of 27 kN/punch, shape of rod; ellipse)
to have obtained tablets each of which weights 1220 mg.
[0066] The obtained tablets were coated by the same operation as in
Example 4 to have obtained film-coated tablets each of which
weights 1255 mg.
Comparison Example 2
[0067] 8430 g of pioglytazon hydrochloride and 2106 g of
microcrystalline cellulose were entered into a mixing machine
(manufactured by POWREX CORPORTION, vertical granulator) and were
mixed while agitating them. The obtained mixture was crushed by the
jet-mill crusher (manufactured by NPK Company, Model 100SP) to have
obtained crushed mixture of pioglytazon hydrochloride and
microcrystalline cellulose.
[0068] 102000 g of metoformin hydrochloride, 2526 g of the crushed
mixture of pioglytazon hydrochloride and microcrystalline
cellulose, and 3164 g of microcrystalline cellulose were entered
into a flow granulating and drying machine (manufactured by POWREX
CORPORTION, MODEL STRE-5M) and were granulated while spraying 33000
g of purified water containing 6600 g of polyvinylpyrrolidone to
have obtained a granule through a drying step.
[0069] 106600 g of the obtained granule was mixed with 7168 g of
microcrystalline cellulose, 5675 g of croscarmellose sodium and
369.3 g of magnesium stearate.
[0070] The obtained powder mixture was made into tablets by using a
tablet-making machine (manufactured by KIKUSUI SEISAKUSHO LTD.,
AQUA0836, 17.5 mm.times.9.5 mm in dimension of tablet, compression
pressure of 20 kN/punch, shape of rod; ellipse) to have obtained
tablets each of which weighs 1070 mg.
[0071] 108100 g of the obtained tablets were thrown into a
film-coating device (manufactured by POWREX CORPORTION, DRS-1200DS)
to coat them by spraying 30310 g of purified water containing 1919
g of hydroxypropylmethyl cellulose, 371 g of polyethylene glycol
6000, 371 g of titanium oxide and 371 g of talc dispersed, at an
inlet temperature of 80 degrees C. in an amount of 200 g/min. Then
film-coated tablets, each of which weights 1100 mg, were
obtained
Comparison Example 3
[0072] 8430 g of pioglytazon hydrochloride and 2106 g of
microcrystalline cellulose were entered into a mixing machine
(manufactured by POWREX CORPORTION, vertical granulator) and were
mixed while agitating them. The obtained mixture was crushed by the
jet-mill crusher (manufactured by NPK Company, Model 100SP) to have
obtained crushed mixture of pioglytazon hydrochloride and
microcrystalline cellulose.
[0073] 93500 g of metoformin hydrochloride, 3936 g of the crushed
mixture of pioglytazon hydrochloride and microcrystalline
cellulose, and 2650 g of microcrystalline cellulose were entered
into a flow granulating and drying machine (manufactured by POWREX
CORPORTION, MODEL STRE-5M) and were granulated while spraying 30855
g of purified water containing 6171 g of polyvinylpyrrolidone to
have obtained a granule through a drying step.
[0074] 99370 g of the obtained granule was mixed with 6650 g of
microcrystalline cellulose, 5280 g of croscarmellose sodium and 350
g of magnesium stearate.
[0075] The obtained powder mixture was made into tablets by using a
tablet-making machine (manufactured by KIKUSUI SEISAKUSHO LTD.,
AQUA0836, 13.5 mm.times.8.5 mm in dimension of tablet, compression
pressure of 14 kN/punch, shape of rod; ellipse) to have obtained
tablets each of which weighs 638 mg.
[0076] 95700 g of the obtained tablets were thrown into a
film-coating device (manufactured by POWREX CORPORTION, DRS-1200DS)
to coat them by spraying 28500 g of purified water containing 1806
g of hydroxypropylmethyl cellulose, 348 g of polyethylene glycol
6000, 348 g of titanium oxide and 348 g of talc dispersed, at an
inlet temperature of 80 degrees C. in an amount of 200 g/min. Then
tablets coated with a film of pharmaceutical composition, each of
which weights 657 mg, were obtained.
Test Example 1
[0077] Twin tablets were selected by an inspection with eyes from
among the film-coated tablets obtained in the above-mentioned
Examples 4, 6 and 7, and Comparison Examples 1 to 3. The number of
occurrence of the twin tablets was divided by the total number of
the tablets and the resulting value was expressed in ppm. The
results are shown in Table 1.
TABLE-US-00001 TABLE 1 Measurement Result of Occurrence Rate of
Twin Tablet Rate of Occurrence of Twin Tablet (ppm) Example 4 0
Example 6 0 Example 7 0 Comparison Example 1 2313 Comparison
Example 2 110 Comparison Example 3 240
[0078] As indicated in Table 1, as for the film-coated tablets
obtained in Examples 4, 6 and 7 (tablets according to the present
invention), no twin tablet occurred and therefore the occurrence of
twin tablet could be completely inhibited. On the other hand, as to
the film-coated tablets of Comparison Example 1 to 3 (standard
elliptical tablets), twin tables occurred in each of them. The
longer the linear portion of the side edge, the higher the
occurrence rate. Particularly, in the case of Comparison Example 1
where the side edge had the longest linear portion, the occurrence
rate was 2313 ppm (about 0.23%).
Test Example 2
[0079] As regards the film-coated tablets obtained in Example 4 and
Comparison Example 1, the thickness and hardness of every tablet
were measured. The result of the measurement was shown in Table
2.
TABLE-US-00002 TABLE 2 Result of Measurement of the Thickness and
Hardness of Tablet Thickness (mm) Hardness (N) Example 4 7.59-7.64
230 Comparison Example 1 7.59-7.74 237
The thickness of tablet: expressed in a range of the values
measured individually of 20 tablets. The hardness of tablet:
expressed by average value of 10 tablets.
[0080] As shown in Table 2, the thickness and hardness of each of
the film-coated tablets (tablets according to the present
invention) obtained in Example 4 were identical to those of the
film-coated tablets (standard elliptical tablets) obtained in
Comparison Example 1. More specifically, since these film-coated
tablets are the same in the aspects of the dimension of tablet
(width and length of tablet), the compression pressure and the
weight, apparently, the tablet of the present invention can retain
its volume large without increasing its thickness as well as the
standard elliptical tablet.
[0081] The tablets explained in the above-mentioned Embodiments and
Examples are exemplified for embodying the technical idea of the
present invention. Therefore, the length, width and thickness of
the tablet are not limited to those of the embodiments but various
changes can be added thereto as far as they fall within a scope of
claims of the present invention.
[0082] For example, in the foregoing Embodiments and Examples, the
radius of curvature of the side edge along the longitudinal
direction of the tablet is set to at least 1.5 times the length of
the tablet and the projected area in plan view is set to at least
97% with respect to the projected area of the standard elliptical
tablet. Accordingly, this is preferable because it is possible to
retain the volume large without increasing the thickness or the
like dimension of the tablet.
[0083] However, the relationship between the radius of curvature of
the side edge and the ratio of the projected area to the standard
elliptical tablet differs depending on the ratio of the tablet
length to the tablet width. When the tablet is short, even if the
radius of curvature is small, the ratio of the projected area can
be set to a large one. Therefore, according to the present
invention, if the projected area in plan is set to at least 97%
with respect to the projected area of the standard elliptical
tablet, the radius of curvature of the side edge may be below 1.5
times the length of the tablet.
[0084] On the contrary, in the case of a longer tablet, the
projected area itself of the standard elliptical tablet occupies
large ratio with respect to a rectangle having the tablet width and
length. In consequence, according to the present invention, if the
radius of curvature of the side edge is set to at least 1.5 times
the length of the tablet, the projected area can be increased with
respect to the rectangle having the tablet width and length.
Accordingly, since it is possible to retain the volume large
without increasing the thickness of the tablet or the like
dimension, the projected area in plan view may be below 97% with
respect to the projected area of the standard elliptical
tablet.
[0085] Further, although the explanation was made for the tablets
each having a smooth surface in the respective embodiments, the
shape of the surface of the tablet is not limited to a specific one
but the tablet may be a divisible one formed with a dividing groove
in its surface as well as the above-mentioned conventional
technique. Besides, the tablet of the present invention may be
printed with a carved seal or a word for distinguishing
purpose.
INDUSTRIAL AVAILABILITY
[0086] The present invention is suitable particularly for the
film-coated tablet because the volume of the tablet can be kept
large without increasing the thickness of the tablet or the like
dimension and a plurality of tablets can be inhibited from sticking
to each other even if they are subjected to a film-coating or the
like treatment so as to improve the yield, but, needless to say, it
is applicable to other tablets.
* * * * *