U.S. patent application number 10/581071 was filed with the patent office on 2007-05-24 for method for treatment of solid pharmaceutical preparation prior to printing and solid pharmaceutical preparation subjected to treatment prior to printing.
Invention is credited to Hiroshi Fukada, Hikaru Fukuyama, Shigeyuki Marunaka, Toshihide Saito.
Application Number | 20070116764 10/581071 |
Document ID | / |
Family ID | 34649985 |
Filed Date | 2007-05-24 |
United States Patent
Application |
20070116764 |
Kind Code |
A1 |
Marunaka; Shigeyuki ; et
al. |
May 24, 2007 |
Method for treatment of solid pharmaceutical preparation prior to
printing and solid pharmaceutical preparation subjected to
treatment prior to printing
Abstract
The present invention provides a method for treating a solid
dosage form to improve the printability and abrasion resistance of
a print to be produced on a surface of the solid dosage form, which
includes treating the surface of the solid dosage form with a
polyethylene glycol-containing aqueous solution before printing; a
production method of a solid dosage form with a printed surface,
which includes printing on the surface after the aforementioned
treatment; and a solid dosage form having a print improved in
abrasion resistance on its surface, which can be obtained by the
aforementioned production method.
Inventors: |
Marunaka; Shigeyuki; (Osaka,
JP) ; Fukuyama; Hikaru; (Osaka, JP) ; Fukada;
Hiroshi; (Osaka, JP) ; Saito; Toshihide;
(Osaka, JP) |
Correspondence
Address: |
FOLEY AND LARDNER LLP;SUITE 500
3000 K STREET NW
WASHINGTON
DC
20007
US
|
Family ID: |
34649985 |
Appl. No.: |
10/581071 |
Filed: |
November 30, 2004 |
PCT Filed: |
November 30, 2004 |
PCT NO: |
PCT/JP04/18112 |
371 Date: |
May 31, 2006 |
Current U.S.
Class: |
424/472 ;
427/2.14 |
Current CPC
Class: |
B41M 5/0011 20130101;
B41M 3/00 20130101; A61K 9/282 20130101; A61K 9/2072 20130101; A61J
3/007 20130101 |
Class at
Publication: |
424/472 ;
427/002.14 |
International
Class: |
A61K 9/28 20060101
A61K009/28; A61K 9/24 20060101 A61K009/24 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 1, 2003 |
JP |
2003-401691 |
Claims
1. A treatment method for improving printability or abrasion
resistance of a print to be produced on a surface of a solid dosage
form, which comprises treating said surface with a polyethylene
glycol-containing aqueous solution before printing.
2. The method of claim 1, wherein polyethylene glycol has an
average molecular weight of not less than about 1,000.
3. The method of claim 1, wherein polyethylene glycol has an
average molecular weight of about 3,000 to about 9,000.
4. The method of claim 1, wherein the amount of polyethylene glycol
to be added by the treatment is about 0.01% to about 1.0% in a
weight ratio to the finished preparation.
5. The method of claim 1, wherein the solid dosage form is a
film-coated tablet.
6. A method for producing a solid dosage form with a printed
surface, which comprises treating the surface of the solid dosage
form with a polyethylene glycol-containing aqueous solution and
then printing on said surface.
7. The method of claim 6, wherein polyethylene glycol has an
average molecular weight of not less than about 1,000.
8. The method of claim 6, wherein polyethylene glycol has an
average molecular weight of about 3,000 to about 9,000.
9. The method of claim 6, wherein the amount of polyethylene glycol
to be added by the treatment is about 0.01% to about 1.0% in a
weight ratio to the finished preparation.
10. The method of claim 6, wherein the solid dosage form is a
film-coated tablet.
11. A solid dosage form treated by the method of claim 1.
12. A solid dosage form with a printed surface, which can be
obtained by the method of claim 6.
13. A solid dosage form which has a coating film comprising
polyethylene glycol but free of bees wax and carnauba wax on its
surface, and is printed on the surface of the coating film.
14. A solid dosage form treated by the method of claim 2.
15. A solid dosage form treated by the method of claim 3.
16. A solid dosage form treated by the method of claim 4.
17. A solid dosage form treated by the method of claim 5.
18. A solid dosage form with a printed surface, which can be
obtained by the method of claim 7.
19. A solid dosage form with a printed surface, which can be
obtained by the method of claim 8.
20. A solid dosage form with a printed surface, which can be
obtained by the method of claim 9.
21. A solid dosage form with a printed surface, which can be
obtained by the method of claim 10.
Description
TECHNICAL FIELD
[0001] The present invention relates to a method for treating a
solid dosage form to improve the printability and abrasion
resistance of a print to be produced on a surface of the solid
dosage form, and a solid dosage form having improved abrasion
resistance of a print or improved printability, which is afforded
by the treatment.
BACKGROUND ART
[0002] There are many kinds of tablets and capsules that resemble
one another in the size, color tone and shape. To identify each
preparation, a company name, a company mark, a product name,
ingredient contents and the like are often coded and directly
imprinted on the preparation. For imprinting, engraving and
printing are available. While engraving is employed for plain
tablets free of coating, a subset of film-coated tablets and the
like, printing is employed for many film-coated tablets,
sugar-coated tablets, capsules and the like.
[0003] For tablets and capsules, polishing with wax (in this
specification, it means "wax" in a narrow sense, namely, fatty acid
ester of higher alcohol; examples: carnauba wax, bees wax and the
like) is often applied for the purpose of increasing the commercial
value by glossy appearance, protecting a preparation from highly
humid environment, preventing staining with coloring agents,
improving slip property to facilitate handling in later operations
of printing, inspection, packing and the like, and the like (e.g.,
Porter and two others, Pan Coating of Tablets and Granules, edited
by Herbert A. Lieberman and one other, Pharmaceutical Dosage Forms
Tablets, vol. 3, US, Marcel Dekker Inc., 1982, p. 92). Wax can be
used by dissolving in an organic solvent such as chloroform/acetone
and the like, or suspending in a dispersion medium such as alcohol
and the like, or directly applied to the surface of a preparation
as a fine powder. However, it is desirable to avoid use of an
organic solvent in view of the safety issue caused by a residual
solvent, a large scale facility required to prevent accident and
environmental pollution, and the like. Moreover, the use of a
suspension and a powder may cause non-uniform coating, possibly
leading to inconvenience.
[0004] Furthermore, polishing with a wax prior to printing may
cause easy scratch of prints and stain of the preparation itself as
well as containers, which in turn impairs identification function
and also reduces the commercial value due to the defective
appearance. In addition, some kind of wax provides too much polish
that can cause printing failure, and decrease the product yield
(e.g., U.S. Pat. No. 4,456,629 (column 1, lines 34-39)).
DISCLOSURE OF THE INVENTION
[0005] It is therefore an object of the present invention to
provide a method of polishing a solid dosage form without using an
organic solvent, which can improve and abrasion resistance of a
print and printability of the solid dosage form, and a solid dosage
form improved in the abrasion resistance of a print and/or
printability based on the method.
[0006] The present inventors have conducted intensive studies in an
attempt to solve the aforementioned problem and surprisingly found
that the printability during printing and abrasion resistance of
the print after printing of a solid dosage form can be remarkably
improved, as compared to conventional tablets polished with a wax,
by treating a surface thereof with a polyethylene glycol-containing
aqueous solution prior to printing. The present inventors have
conducted further studies based on these findings and completed the
present invention.
[0007] Accordingly, the present invention provides [0008] [1] a
treatment method for improving printability and/or abrasion
resistance of a print to be produced on a surface of a solid dosage
form, which comprises treating said surface with a polyethylene
glycol-containing aqueous solution before printing, [0009] [2] the
method of the above-mentioned [1], wherein polyethylene glycol has
an average molecular weight of not less than about 1,000, [0010]
[3] the method of the above-mentioned [1], wherein polyethylene
glycol has an average molecular weight of about 3,000 to about
9,000, [0011] [4] the method of the above-mentioned [1], wherein
the amount of polyethylene glycol to be added by the treatment is
about 0.01% to about 1.0% in a weight ratio to the finished
preparation, [0012] [5] the method of the above-mentioned [1],
wherein the solid dosage form is a film-coated tablet, [0013] [6] a
method for producing a solid dosage form with a printed surface,
which comprises treating the surface of the solid dosage form with
a polyethylene glycol-containing aqueous solution and then printing
on said surface, [0014] [7] the method of the above-mentioned [6],
wherein polyethylene glycol has an average molecular weight of not
less than about 1,000, [0015] [8] the method of the above-mentioned
[6], wherein polyethylene glycol has an average molecular weight of
about 3,000 to about 9,000, [0016] [9] the method of the
above-mentioned [6], wherein the amount of polyethylene glycol to
be added by the treatment is about 0.01% to about 1.0% in a weight
ratio to the finished preparation, [0017] [10] the method of the
above-mentioned [6], wherein the solid dosage form is a film-coated
tablet, [0018] [11] a solid dosage form treated by the method of
any of the above-mentioned [1] to [5], [0019] [12] a solid dosage
form with a printed surface, which can be obtained by any of the
above-mentioned [6] to [10], [0020] [13] a solid dosage form which
has a coating film comprising polyethylene glycol but free of bees
wax and carnauba wax on its surface, and is printed on the surface
of the coating film, and [0021] [14] a solid dosage form which has
a coating comprising polyethylene glycol but free of bees wax and
carnauba wax on its surface, and is printed on the surface of the
coating.
DETAILED DESCRIPTION OF THE INVENTION
[0022] The present invention provides a method for treating a solid
dosage form to improve the abrasion resistance of a print to be
produced on a surface of the solid dosage form. As used herein, by
"to improve the abrasion resistance of a print" is meant, for
example, significantly reducing the degree of abrasion of the print
produced on the solid dosage form as compared to a case free of
such treatment, in the print abrasion test to be described in
detail in the Examples to be mentioned below.
[0023] The solid dosage form applicable to the treatment method of
the present invention is not particularly limited in the dosage
form as long as its surface can be printed on and, for example,
tablet, capsule, troche, pill, suppository and the like can be
mentioned. In view of the necessity of imprinting by printing, the
method is particularly preferably applied to tablets and
capsules.
[0024] In this specification, the "solid dosage form" means not
only pharmaceutical products but also any composition processed to
have a certain dosage form of animal drug, agricultural chemical,
fertilizer, sanitary products and the like.
[0025] The active ingredient to be contained in the solid dosage
form is not particularly limited. For example, substances effective
for the prophylaxis or treatment of various diseases, which are
exemplified by, but not limited to, substances having
sleep-inducing action, tranquilizer activity, antibiotic activity,
hypotensive action, antianginal activity, analgesic activity,
anti-inflammatory activity, mental stabilizing action, diabetes
treatment activity, diuretic action, anticholine activity,
antihyperacidic action, antiepileptic action, ACE inhibitory
activity, .beta.-receptor antagonistic or agonistic activity,
anesthetic action, anorexigenic action, antiarrhythmic action,
antidepressive action, anticoagulant activity, anti diarrheal
action, antihistaminic activity, antimalarial action, antitumor
activity, immunosuppressive activity, anti-Parkinson's syndrome
action, antipsychotic action, antiplatelet activity,
antihyperlipidemic action and the like, and the like, substance
having detergent action, substances having flavoring, fertilizer,
and deodorizing actions, animal/pest exterminating substances,
substances having insecticidal action, substances having herbicidal
action, plant growth regulators and the like.
[0026] Where necessary, the solid dosage form of the present
invention can contain a carrier acceptable for the use of the solid
dosage form, together with the active ingredient. In the case of a
pharmaceutical preparation, for example, it can contain a
pharmaceutically acceptable carrier. As the pharmaceutically
acceptable carrier, various organic or inorganic carriers
conventionally used as preparation materials are used and, for
example, excipient, lubricant, binder, disintegrant, thickener and
the like are appropriately added in suitable amounts. Where
necessary, additives such as preservative, antioxidant, coloring
agent, sweetening agent and the like can also be used.
[0027] Examples of the excipient include, but are not limited to,
lactose, sucrose, glucose, maltose, corn starch, flour starch,
mannitol, xylitol, sorbitol, maltitol, erythritol, lactitol,
palatinit, crystalline cellulose, light anhydrous silicic acid,
dextrin, carboxymethylstarch, gelatin, synthesis aluminum silicate,
magnesium alumino metesilicate, magnesium oxide, calcium phosphate,
calcium carbonate, calcium sulfate and the like.
[0028] Examples of the lubricant include, but are not limited to,
stearic acid, magnesium stearate, calcium stearate, talc, waxes,
DL-leucine, sodium lauryl sulfate, magnesium lauryl sulfate,
polyethylene glycol, aerosil (usable as antistatic agent) and the
like.
[0029] Examples of the binder include, but are not limited to,
gelatin, pullulan, hydroxypropylmethylcellulose (HPMC),
hydroxypropylcellulose (HPC), methylcellulose (MC), crystalline
cellulose, polyvinylpyrrolidone (PVP), polyethylene glycol, gum
arabic, dextran, polyvinyl alcohol (PVA), starch paste and the
like.
[0030] Examples of the disintegrant include, but are not limited
to, carboxymethylcellulose, calcium carboxymethylcellulose,
low-substituted hydroxypropylcellulose, crosslinking
polyvinylpyrrolidone, carmellose sodium, croscarmellose sodium,
sodium carboxymethyl starch, cation exchange resin, partially
pregelatinized starch, corn starch and the like.
[0031] Examples of the thickener include, but are not limited to,
natural rubbers, cellulose derivative, acrylic acid polymer and the
like.
[0032] Examples of the preservative include, but are not limited
to, p-hydroxybenzoic acid esters, chlorobutanol, benzyl alcohol,
phenethyl alcohol, dehydroacetic acid, sorbic acid and the
like.
[0033] Examples of the antioxidant include, but are not limited to,
sulfite, ascorbic acid and their alkali metal salts, alkaline earth
metal salts and the like.
[0034] Examples of the coloring agent include, but are not limited
to, synthetic coloring agents applicable to pharmaceutical products
(e.g., sunset yellow etc. and aluminum lake thereof and the like),
yellow ferric oxide, red ferric oxide, riboflavin, riboflavin
organic acid esters (e.g., riboflavin butyric acid ester),
phosphoric acid riboflavin or alkali metal salt thereof, alkaline
earth metal salt, phenol phthalein, titanium oxide and the like. As
the light shielding agent, titanium oxide and the like can be
mentioned.
[0035] Examples of the sweetening agent include, but are not
limited to, saccharin sodium, dipotassium glycyrrhizinate,
aspartame, stevia and the like.
[0036] The solid dosage form of the present invention can be
formulated into a dosage form suitable for oral administration,
which is exemplified by, but not limited to, tablet, capsule and
the like or parenteral administration such as suppository and the
like, by processing the above-mentioned active ingredient and a
suitable carrier according to a method known per se.
[0037] Tablets can be coated by a method known per se for the
purpose of masking a smell or taste, stabilizing components,
maintaining efficacy and the like. The coating can be largely
divided into sugar coating and film coating (including enteric
coating and the like) according to its kind.
[0038] As a coating agent for sugar coating, sucrose is generally
used. To enhance the binding property of a sugar coating layer and
increase the mechanical strength, gelatin, gum arabic,
methylcellulose, carboxymethylcellulose, sodium
carboxymethylcellulose, sodium starchglycolate, crystalline
cellulose, polyvinylpyrrolidone, polyvinyl alcohol, sodium alginate
and the like can be added. Furthermore, as an excipient or
anti-tack agent, talc, precipitated calcium carbonate, kaolin and
the like are used, and, for masking or shading of color, a masking
agent such as titanium oxide and the like are used.
[0039] As the film coating agent, for example,
hydroxypropylmethylcellulose, ethylcellulose,
hydroxypropylcellulose, tween80, and dyes such as titanium oxide,
ferric oxide (e.g., red ferric oxide, yellow ferric oxide) and the
like are used. Moreover, photostability and the like can be
improved by adding a masking agent and the like. These film coating
formulations may contain, where necessary, talc and other
excipients applicable to pharmaceutical products. As the film
coating agent, a base agent aiming at enteric coating and
controlled release may be used besides those used for masking a
taste, enhancing photostability or improving appearance. As a base
agent for the film coating, hydroxypropylcellulose (HPC),
hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP),
ethylcellulose, polyvinyl acetal diethylamino acetate, cellulose
acetate phthalate, methacrylic acid copolymers (e.g., methyl
methacrylate-methacryl acid copolymers (Eudragit L100 or S100,
manufactured by Rohm), methacrylic acid-ethyl acrylate copolymers
(Eudragit L100-55, L30D-55), methacrylic acid-methyl
acrylate-methyl methacrylate copolymers (Eudragit FS30D,
manufactured by Rohm)), hydroxypropylmethylcellulose phthalate
(HP-55, HP-50, manufactured by Shin-Etsu Chemical Co., Ltd.),
carboxymethylethylcellulose (CMEC, manufactured by Freund
Corporation), hydroxypropylcellulose acetate succinate (HPMCAS,
manufactured by Shin-Etsu Chemical Co., Ltd.), polyvinyl acetate
phthalate, shellac and the like can be used. They may be used
alone, or at least two or more kinds of polymers may be applied in
combination, or at least two or more kinds of polymers may be
applied successively.
[0040] Of these, as a coating material for controlling the release
of the active ingredient in a pH-dependent manner,
hydroxypropylmethylcellulose phthalates (HP-55, HP-50, manufactured
by Shin-Etsu Chemical Co., Ltd.), cellulose acetate phthalate,
carboxymethylethylcellulose (CMEC, manufactured by Freund
Corporation), methyl methacrylate-methacrylic acid copolymers
(Eudragit L100 or S100, manufactured by Rohm), methacrylic
acid-ethyl acrylate copolymers (Eudragit L100-55, L30D-55),
methacrylic acid-methyl acrylate-methyl methacrylate copolymer
(Eudragit FS30D, manufactured by Rohm), hydroxypropylcellulose
acetate succinate (HPMCAS, manufactured by Shin-Etsu Chemical Co.,
Ltd.), polyvinyl acetate phthalate, shellac and the like can be
used.
[0041] The coating agents may be used alone or in combination as
necessary. Where necessary, plasticizer, stabilizer and the like
such as polyethylene glycol, dibutyl sebacate, diethyl phthalate,
triacetine, triethyl citrate, copolyvidon and the like may be used
for coating.
[0042] For coating, a method known per se, such as a pan coating
method using a perforated coating system (e.g., Hicoater
(trademark); Freund Corporation) and the like using a coating pan,
a fluid bed coating method using a fluid bed granulation coating
system (e.g., flow coater (trademark); Freund Corporation) and the
like, is employed.
[0043] Capsules can be produced by packing the above-mentioned
active ingredient powder, or a powder mixture of the active
ingredient and the above-mentioned carrier, or fine granules or
granules obtained by kneading or granulating the powder mixture and
the like in a suitable capsule. The packed material (particularly
fine particles or granules) may be film-coated as necessary, in a
similar manner as that mentioned above with regard to the
tablet.
[0044] As the capsule, one containing polyhydric alcohol such as
glycerol, propylene glycol and the like or saccharide such as
mannitol, sorbit and the like as a plasticizer in gelatin, which is
molded suitably can be mentioned. Where necessary, the capsule may
further contain a coloring agent and a preservative similar to
those mentioned above.
[0045] The treatment method of the present invention may be applied
to a capsule filled with the packing material such as an active
ingredient and the like. Alternatively, an empty capsule may be
subjected to the treatment method of the present invention, printed
and filled with a packing material to give a finished
preparation.
[0046] The treatment method of the present invention can also be
applied not only to the above-mentioned solid dosage form but also
any solid composition desired to carry a print on its surface such
as a food (e.g., sugar coated chocolate, gum, supplement and the
like) and the like, particularly a solid composition requiring or
desirably subjected to a treatment for improving the slip property
and gloss.
[0047] The treatment method of the present invention is
characterized by a treatment of a surface of the solid dosage form
with a polyethylene glycol-containing aqueous solution before
printing. As used herein, by the "treatment" is meant "to apply"
and refers to bringing a polyethylene glycol-containing aqueous
solution into contact with the surface of a solid dosage form after
treatment, such that polyethylene glycol remains on the
surface.
[0048] Polyethylene glycol to be used in the present invention is
not particularly limited as long as it is not subject to any
limitation due to other reasons (e.g., range acceptable as a
pharmaceutical additive when the solid dosage form is a
pharmaceutical preparation). In consideration of the object of the
present invention to improve durability of a print, however,
polyethylene glycol is desirably present as a solid at a
temperature of the environment (e.g., 0 to 40.degree. C., 10 to
30.degree. C., 15 to 25.degree. C.) where the solid dosage form is
preserved. For example, one having an average molecular weight of
about not less than 1,000, more preferably about 3,000 to about
9,000, can be mentioned. In addition, two or more kinds of
polyethylene glycol having different average molecular weights may
be used in a mixture.
[0049] The average molecular weight of polyethylene glycol is
measured by a method according to the measurement method of the
average molecular weight of macrogol 4000 in the Japan
Pharmacopoeia fourteenth Edition (hereinafter sometimes to be
abbreviated simply as the Japan Pharmacopoeia).
[0050] The concentration of polyethylene glycol in the polyethylene
glycol-containing aqueous solution is not particularly limited as
long as it ensures that polyethylene glycol remains on the surface
of a solid dosage form after treatment in an amount sufficient to
improve the abrasion resistance of a print to be produced on said
surface. For example, it is about 1 to about 20 wt %, preferably
about 5 to about 15 wt %.
[0051] The polyethylene glycol-containing aqueous solution can
contain a component other than polyethylene glycol within the range
free of a bad influence on the property of a print to be produced
on the surface of a solid dosage form. As used herein, by the
"property of a print" is meant properties including quantitative
and qualitative characteristics during printing, such as abrasion
resistance after printing, incidence of incomplete print, printing
stain and the like (=rate of printing failure) and level of the
printing failure. For example, when the treatment method of the
present invention is applied to a plain tablet, the polyethylene
glycol-containing aqueous solution contains a film coating agent
since the solution also functions as a film coating liquid, as
mentioned above. As the film coating agent, for example, those
capable of being dispersed in a water-soluble or aqueous solution
can be mentioned, from the above-mentioned film coating agents.
[0052] In addition, the polyethylene glycol-containing aqueous
solution can further contain a preparation additive as necessary,
such as stabilizer, lubricant, preservative, antioxidant, coloring
agent, sweetening agent and the like. As the stabilizer, for
example, tartaric acid, citric acid, succinic acid, fumaric acid,
maleic acid and the like can be mentioned. As the lubricant, for
example, talc, titanium oxide, magnesium stearate, calcium
stearate, light anhydrous silicic acid and the like can be
mentioned. As the preservative, for example, p-hydroxybenzoic acid
esters, chlorobutanol, benzyl alcohol, phenethyl alcohol,
dehydroacetic acid, sorbic acid and the like can be mentioned. As
the antioxidant, for example, sulfite, ascorbate and the like can
be mentioned. As the coloring agent, for example, water-soluble
food tar colors (e.g., food dyes such as Food Red No. 2 and No. 3,
Food Yellow No. 4 and No. 5, Food Blue No. 1 and No. 2 and the
like), water insoluble lake colors (e.g., aluminum salts of the
aforementioned water-soluble food tar colors), natural colors
(e.g., B-carotene, chlorophyll, ferric oxide) and the like can be
mentioned. As the sweetening agent, for example, sodium saccharin,
dipotassium glycyrrhizinate, aspartame, stevia and the like can be
mentioned.
[0053] As mentioned above, the film coating liquid can contain a
plasticizer to control the softening temperature of the coating
agent. When the polyethylene glycol-containing aqueous solution is
a film coating liquid, polyethylene glycol itself can function as a
plasticizer. A polyethylene glycol-containing aqueous solution
having a concentration necessary for improving the abrasion
resistance of a print to be produced on the surface of a solid
dosage form is sufficient to function as a plasticizer. When
desired, other plasticizers, such as acetyltributyl citrate,
acetyltriethyl citrate, castor oil, diacetylation monoglyceride,
dibutyl sebacate, diethyl phthalate, glycerol, mono- or
di-acetylation monoglyceride, propyleneglycol, triacetine, triethyl
citrate and the like may be further added.
[0054] When the polyethylene glycol-containing aqueous solution
contains a component other than polyethylene glycol, the proportion
of polyethylene glycol in the whole components (excluding water) is
about 1 to about 30 wt %, preferably about 10 to about 20 wt %.
[0055] For a treatment of the surface of a solid dosage form with a
polyethylene glycol-containing aqueous solution, various coating
methods generally used in the field of preparations can be
employed. Preferably, spray coating is applied using a coating pan,
a fluid bed coating system and the like.
[0056] In the case of sugar-coated tablets, for example, after
completion of each step of sugar coating (i.e., waterproof coating,
under coating, sub-coating, coloring, finishing), tablets are
transferred to a cloth polishing pan, a predetermined amount of a
polyethylene glycol-containing aqueous solution is sprayed or
poured thereon while rotating the pan, or a polyethylene
glycol-containing aqueous solution is sprayed or poured thereon
once to several times while rotating the pan until it reaches a
predetermined coating weight.
[0057] In the case of film-coated tablets, for example, a
polyethylene glycol-containing aqueous solution is sprayed with a
compressed air from a spray nozzle in the coating pan used for the
film coating while rotating the pan, and the surface of the tablets
is dried by heated air supplied. Alternatively, in the fluid bed
coating system used for the film coating, a polyethylene
glycol-containing aqueous solution is sprayed from a spray nozzle
while floating or fluidizing the tablets with an air flow and the
surface of the tablets is dried with the air flow. The polyethylene
glycol-containing aqueous solution is sprayed in a predetermined
amount, or the above-mentioned operation is repeated until a
predetermined coat weight is achieved.
[0058] In the case of plain tablets, namely, when a polyethylene
glycol-containing aqueous solution also functions as a film coating
liquid, a method employed for conventional film coating can be used
directly. For example, a method similar to that of the
above-mentioned film-coated tablets can be mentioned.
[0059] In the case of capsule, too, a method employed for
conventional film coating can be used similarly. When this
treatment is applied after filling packing materials such as an
active ingredient and the like, powder of the packing materials
attached to the surface of the capsule during the filling is
preferably removed with a conventional capsule polishing machine
before the treatment.
[0060] The weight of the coating film formed by the treatment
method of the present invention is not particularly limited as long
as it ensures that polyethylene glycol remains on the surface of a
solid dosage form after treatment in an amount sufficient to
improve the abrasion resistance of a print to be produced on said
surface. Preferably, it is appropriately selected from the range
that makes the weight ratio of the amount of polyethylene glycol to
be added by this treatment to the finished preparation fall within
the range of about 0.01 to about 1.0%, more preferably about 0.05
to about 0.7%.
[0061] The treatment method of the present invention can not only
improve the abrasion resistance of a print to be produced on the
surface of a solid dosage form, but also reduce the frequency of
printing failure (i.e., printing failure rate) during printing such
as incomplete print, printing stain and the like, and
advantageously further improve the printing performance as a
whole.
[0062] Accordingly, the present invention also relates to a
production method of a solid dosage form having a print on its
surface, which comprises treating the surface of the solid dosage
form with a polyethylene glycol-containing aqueous solution and
then printing on said surface. The treatment with a polyethylene
glycol-containing aqueous solution can be applied as mentioned
above.
[0063] For printing, a method conventionally used in the art can be
employed. As a solid dosage form delivery mechanism of a printing
machine, any type can be used, including a slot type, a drum type,
a link type and the like, and an appropriate type can be selected
according to the manufacturing scale and the like. While the
printing method is not particularly limited, either, a photogravure
offset printing method is often used. To be specific, a
photogravure roll engraved with an identification code, a symbol
and the like during a photomechanical process is rotated in an ink
tank to attach the ink, and redundant ink is scraped off with a
blade (thin-bladed knife). The ink remaining in the engraving
(concave) is transferred onto a rubber offset roll, and then
transferred onto the solid dosage form in a printing section to
complete the printing. As the tablet (capsule) printing machine,
commercially available ones from Markem Corporation, Hartnett,
Matsuoka Machinery Works Co., Ltd, Qualicaps Co., Ltd. and the like
can be used.
[0064] While the ink to be used for printing is not particularly
limited as long as it is harmless, it is desirably quick-drying,
and has high abrasion resistance after drying.
[0065] As the dye, titanium oxide, carbon black, iron oxide, tar
dyes (e.g., acidic colors such as Red No. 2, Red No. 3, Red No.
102, Red No. 104-(1), Red No. 105-(1), Red No. 106, Yellow No. 4,
Yellow No. 5, Green No. 5, Blue No. 1, Blue No. 2 and the like) and
the like are generally used. As the base agent, moreover, shellac
and the like are used and, as the solvent, ethanol, n-butanol,
isopropanol and the like are used.
[0066] The solid dosage form with a print on its surface, which is
produced by the above-mentioned method, has novel and useful
characteristic in that it shows remarkably improved abrasion
resistance of prints as compared to conventional preparations
obtained by applying, before printing, a polishing treatment with a
wax solution using an organic solvent or a powder wax or a wax-like
substance. Accordingly, the present invention also provides a solid
dosage form obtained by the above-mentioned method, which has a
print on its surface.
[0067] The solid dosage form of the present invention can be
conferred a desirable characteristic of superior abrasion
resistance of a print produced on its surface, due to the presence
of a coating film containing polyethylene glycol on the surface of
the solid dosage form. The "coating film" does not need to
completely cover the surface of a solid dosage form, as long as
polyethylene glycol is substantially uniformly present at least on
the area to be printed on. For example, the "coating film" may be
in the state where a number of miniature films attach to the
surface of a solid dosage form. As used herein, by "substantially
uniform" is meant being uniform to a degree sufficient to improve
the abrasion resistance of the print. Therefore, the solid dosage
form of the present invention is not restricted to the
above-mentioned method, as long as it has the above-mentioned
surface structure and superior abrasion resistance of the print,
and may be produced by any method.
[0068] Preferably, the solid dosage form of the present invention
does not contain bees wax and carnauba wax in the coating film
containing polyethylene glycol.
[0069] The solid dosage form of the present invention can be
administered to the subject in the same manner as in conventional
solid dosage forms.
[0070] The present invention is explained in detail in the
following by referring to Examples, which are mere examples and do
not limit the scope of the present invention in any way.
EXAMPLE 1
Reference Example
Production of Film-coated Tablet Formulation (Unit: mg)
[0071] TABLE-US-00001 plain tablet 130.0 (containing 4 mg of active
ingredient) hydroxypropylmethylcellulose 3.74 (74.8%) (TC-5;
trademark) copolyvidon 0.75 (15.0%) titanium oxide 0.5 (10.0%)
yellow ferric oxide 0.01 (0.2%) total 135.0
[0072] Plain tablets were placed in a coating machine (Driacoater
(Powrex Corporation) or Hicoater (Freund Corporation)), a film
coating liquid containing TC-5, copolyvidon, titanium oxide and
yellow ferric oxide at the above-mentioned weight ratios was
sprayed with a spray nozzle while rotating the pan, and the tablets
were dried by heated air supplied. This operation was repeated
until the above-mentioned coating weight was achieved.
EXAMPLE 2
[0073] Pre-printing Treatment with Polyethylene Glycol-containing
Aqueous Solution Formulation (Unit: mg) TABLE-US-00002 Prepar. Ex.
1 Prepar. Ex. 2 Comp. Ex. film-coated tablet 135.0 135.0 135.0
(Reference Example) MACROGOL 4000 0.1 (the Japan Pharmacopoeia)
MACROGOL 6000 0.1 (the Japan Pharmacopoeia) water (0.9) (0.9)
carnauba wax 0.008 sorbitan mono-oleate 0.04 n-hexane (0.9625)
[0074] The film-coated tablets (6,000 tablets, 810 g) obtained in
the above-mentioned Reference Example were placed in a Hicoater
(Freund Corporation), and a 10 wt % aqueous solution of MACROGOL
4000 (the Japan Pharmacopoeia; molecular weight 2,600-3,800)
(Preparation Example 1) or MACROGOL 6000 (the Japan Pharmacopoeia;
molecular weight 7,300-9,300) (Preparation Example 2) in total 6.0
g, or a 0.79 wt % carnauba wax n-hexane solution (Comparative
Example) in total 6.063 g was sprayed with a spray nozzle while
rotating the pan to give respective tablets having the
above-mentioned formulations.
[0075] The above-mentioned respective tablets were printed on by a
conventional method using an organic solvent type ink (manufactured
by Colorcon. Inc.) with a tablet printing machine (Matsuoka
Machinery Works Co., Ltd).
EXAMPLE 3
Experimental Example
Test of Print Abrasion Resistance of and Printing Failure Rate
[0076] The three kinds of tablets (500 tablets each) obtained in
the above-mentioned Example 2 were visually observed to examine
printing failure, and 100 tablets each were placed in 3K glass
bottles, which were shaken at amplitude 40 mm, shaking speed 250
times/minute in a reciprocal shaker SR-IIw (Nihon Medical and
Chemical instruments Co., Ltd.) to observe the level of abrasion of
the print over time. The results are shown in Table 1.
TABLE-US-00003 TABLE 1 Comp. Ex. Prep. Ex. 1 Prep. Ex. 2 appear-
number of 500 500 500 ance test tablets Class D 0 0 0 (%).sup.1)
Class C 0 0 0 (%) Class B in- 2.0 0 0 (%) complete print printing
1.4 1.2 0.8 stain total 3.4 1.2 0.8 abrasion 10 min print is no
change (.+-.) no change (.+-.) property.sup.2) scratchy, whole
tablet is stained (+) 30 min print is print is no change (.+-.)
scratchy, scratchy, whole whole tablet is tablet is stained (++)
stained (+) 60 min print is print is print is scratchy, scratchy,
scratchy, whole whole whole tablet is tablet is tablet is stained
(+++) stained, stained, cloudy cloudy bottle (++) bottle (++)
.sup.1)Class of appearance Class B: readable print though partly
missing, or printing stain of not more than 1 mm in length Class C:
partly unreadable print, or printing stain of more than 1 mm in
length Class D: unreadable print .sup.2)Abrasion property (.+-.):
No change from the start of shaking (+): readable print though with
slight change in printing state (scratching, stain and the like)
(++): clear change in printing state and partly unreadable print
(+++): marked change in printing state and mostly unreadable
print
[0077] As is clear from Table 1, a pretreatment with a polyethylene
glycol-containing aqueous solution resulted in remarkably improved
abrasion resistance of the print as compared to the use of carnauba
wax. Moreover, the printing failure rate showed a tendency toward
lower levels. More superior results were obtained in both the
abrasion resistance and printing failure rate by the use of
MACROGOL 6000.
INDUSTRIAL APPLICABILITY
[0078] According to the treatment method of the present invention,
printability and abrasion resistance of a print to be produced on a
surface of the solid dosage form can be improved, and as a result,
identification function of the solid dosage form can be maintained
for a long time and good appearance is not impaired, and a solid
dosage form with a high commercial value can be provided.
[0079] The method for treating a solid dosage form of the present
invention provides an effect of remarkably improved printability
and abrasion resistance of the solid dosage form by treating,
before printing, the surface of the solid dosage form with a
polyethylene glycol-containing aqueous solution.
[0080] While some of the embodiments of the present invention have
been described in detail in the above, it is, however, possible for
those of ordinary skill in the art to make various modifications
and changes to the particular embodiments shown without
substantially departing from the teaching and advantages of the
present invention. Such modifications and changes are encompassed
in the spirit and scope of the present invention as set forth in
the appended claims.
[0081] Those described in a singular form in the present
specification may be understood in a plural form, as long as they
are not associated with clear inconsistencies with the context and
the present invention.
[0082] All references cited herein, including patents and patent
applications, are hereby incorporated in full by reference, to the
extent that they have been disclosed herein.
[0083] This application is based on a patent application No.
2003-401691 filed in Japan, the contents of which are incorporated
in full herein by this reference.
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