JPH0853345A - Divisible tablet provided with film coating - Google Patents

Abstract

PURPOSE:To obtain the subject tablet excellent in the easiness/uniformity of division, thus useful as a tablet for medicinal use, by making both the upper and lower surfaces of a plate-like raw tablet with a cracking line for facilitating its division to specific designs, respectively, followed by providing these surfaces with film coating without trouble. CONSTITUTION:The upper surface (r) of a plate-like raw tablet with a cracking line for facilitating its division is gradually recessed from the opposing edges toward the cracking line, and the lower surface R of this raw tablet is gradually raised from the periphery toward the center so as to get thinner in the wall thickness of the peripheral part than that of the central part, followed by providing these surfaces with film coating, thus obtaining the objective tablet. In this case, it is preferable that the resultant upper and lower surfaces (r) and R be curved with the radius of curvature of the upper surface (r) smaller than that of the lower surface R.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a film-coated divided tablet which can be uniformly and easily divided, and which is devised so as not to cause troubles during the film coating process, preferably a pharmaceutical divided tablet. It is a thing.

[0002]

2. Description of the Related Art Divided tablets are tablets that are divided by a pharmacist at the time of dispensation or by the patient himself at the time of dosing, depending on the dose, in order to optimize the dose management for individual patients and increase flexibility in prescription. Developed in. Divided tablets are usually constructed by providing one or more notches (dividing lines) on the tablet surface. An example of a divided tablet is, for example, JP-A-61
See -289027.

By the way, in order to mask the unpleasant odor and taste of the active ingredient of the drug and to secure the stability against light and the like, it is desirable to coat the tablets with a film. However, despite the large number of scored tablets on the market and the large number of reports on split tablets, the split tablets coated with a film have not been put into practical use. As its cause, the following various problems in the production of film-coated divided tablets have been pointed out.

1) In the film coating process
Various troubles When film coating is applied to normal divided tablets, twinning (a phenomenon that adjacent films stick to each other and the tablets stick to each other) during the process, core erosion (abrasiveness of uncoated tablets), edge chipping Various problems such as (a phenomenon in which the edge portion is chipped) occur.

2) Difficulty of division Usually, as a division operation, a method in which a pharmacist or a patient holds a tablet with both hands to open (or close) the score line,
Alternatively, a method of pressing on a hard flat surface such as a desk is used. However, this method has a problem in that it is difficult to divide a divided tablet, which tends to be downsized in recent years. In such a situation, the division of the divided tablets becomes more and more difficult because the film coating on the divided tablets requires more force for division. Furthermore, from the viewpoint of hygiene, it is preferable that the tablets can be divided from the packaging such as PTP (vinyl chloride / vinylidene chloride composite sheet) so that they can be taken out from the container without being touched directly. The division of requires more power.

With the aging of society and the increasing chances of administration of drugs to old people, the development of products that are easy to use is becoming more and more important.

3) Since the film is not completely divided along the dividing line when the film is divided, there is a problem in the appearance and shape after the division.

4) Non-uniform division of tablets The advantage of divided tablets is that the dosage can be precisely controlled.
However, due to the fact that the film coating requires a strong force at the time of division, the division is likely to be non-uniform, and the above advantages may be lost.

It is often the case that the tablets to be dividedly administered contain a component having a strong pharmacological action such as an antianginal drug, an antihypertensive agent, an antiarrhythmic agent, and the even division of the divided tablets is a very important problem. Is.

As described above, the divided tablets coated with the film are difficult to manufacture, and have not been put into practical use in spite of the necessity.

[0011]

SUMMARY OF THE INVENTION An object of the present invention is to put a film-coated divided tablet into practical use. More specifically, the present invention provides a divided tablet devised so as not to cause troubles such as the above twinning during the film coating process.

The present invention further provides a film-coated split tablet, which is easy to split and can be split together with the tablet whose film is broken during splitting so that the dosage can be split accurately.

The present invention further provides a film-coated divided tablet which allows easy division of even small particles.

The present invention further provides film-coated split tablets which are easily split before removal from the PTP packaging.

[0015]

The dividable tablet provided with the film coating of the present invention is a disc-shaped tablet provided with a score line consisting of at least one groove on the upper surface and / or the lower surface for facilitating the splitting of the tablet. The uncoated tablet of
Gradually indent from the opposite edge toward the score line, and gradually raise the lower surface from the peripheral part toward the central part, provided that the central part is thinner than the peripheral part, and the film It is characterized by being coated. It is important to prevent the risk of twinning during film coating from occurring by providing a difference in the degree of depression of the upper surface of the tablet and the degree of swelling of the lower surface so that the central portion is thinner than the peripheral portion. In this specification, the surface of the upper punch is the upper surface and the surface of the lower punch is the lower surface.

The specific shapes of the depressions and swells may be appropriately determined, but in a preferred embodiment, the split tablet of the present invention has at least a recess having a bowl-shaped curved surface on the upper surface thereof and at least splitting of the tablet. One groove is formed, a convex portion having a hill-like curved surface is formed on the lower surface, and the radius of curvature of the upper surface is made smaller than the radius of curvature of the lower surface. The radius of curvature of the upper surface depends on the size of the tablet, but is preferably 6 to 14 mm for a tablet having a diameter of 8 mm, and the radius of curvature of the lower surface is preferably 10 to 20 mm.

The split tablet of the present invention can have any shape such as a circle, an ellipse, a polygon, or a star when viewed from above and below. It is convenient to make it circular or elliptical. The size of the tablet may be large or small, for example, a diameter of 6 mm to 10 mm, or a smaller tablet of 3 mm to 6 mm.
The thickness of the tablet may be 3 to 5 mm as a value measured as the distance between the uppermost part of the upper surface and the lowermost part of the lower surface, in consideration of the composition of the plain tablet and the ease of division.

In the case of a circular tablet, at least one groove for facilitating division is formed substantially along the diametrical direction of the upper surface having a recess. When it is desired to divide a circular tablet into four, two grooves are formed along the diametrical direction and orthogonal to each other. In the case of an elliptical tablet, it may be formed along either the major axis direction or the minor axis direction. The cut end of the groove is preferably V-shaped or U-shaped. Further, in order to prevent damage to the corners of the edge portion when the tablet is processed, the circumferences of the upper and lower surfaces and the corners of the groove may be lightly shaved.

The tablet of the present invention, due to the above-mentioned constitution, can not only prevent twining during film coating but also can be easily divided by placing it on a flat surface such as a table upside down and pressing it from above to apply pressure. You can

A preferred embodiment of the present invention is shown in FIG. 1 (upper punch: V
Slit line edge angle Lower punch: R edge angle). In this figure, a is a view from the bottom, b is a view from the top, and c is a side view from the direction in which the groove runs. The split tablet of the present embodiment belongs to a lower punch-shaped karate type (tablet shape in which the upper surface of the tablet is inclined from the edge toward the dividing line).
R represents the radius of curvature of the lower surface, r represents the radius of curvature of the upper surface, and R>
r. By applying such a shape, all coating troubles such as twinning, core erosion and edge chipping during film coating are eliminated (see below, Table 2), and the fragility at the time of splitting is more than that of the conventional typical split tablet. Improved (see below, Table 3).

The coating applied to the tablet of the present invention may be one that is commonly used for coating tablets, but the present inventors have also investigated a coating agent suitable for use in divided tablets. According to the result, the coating applied to the divided tablets preferably has the following physical properties when formed into a film having a thickness of 50 μm.
The tensile strength is preferably 250 kg / cm ^{2 to} 45
0 kg / cm ² , more preferably 300 kg / cm ² to 4
It is 50 kg / cm ² . Elongation is preferably 1.0%
˜4.0%, more preferably 1.5% to 3.5%.

When the tablet of the present invention is coated with the coating having two physical properties defined in the above-mentioned preferred ranges, the tablet covered with the film can be easily divided. The film can be neatly divided without peeling off the film at the time of division or sticking to the divided uncoated tablet which is unevenly stretched, so that a dose deviation is less likely to occur.

Non-limiting examples of film-forming polymers that can be used to form the preferred film coatings described above include cellulose ether-based polymers. The cellulose ether-based polymer has a molecular weight of 12,000 to 120,000 and a viscosity of 2.5 to 18 cSt (25 ° C). The cellulose ether-based polymer includes hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose, methyl cellulose and the like. Preferred is HPMC. As HPMC, for example, TC-5 (Japanese Pharmacopoeia hydroxypropyrimethylcellulose 2910) can be used.

To apply film coating to plain tablets,
The cellulose ether-based polymer is preferably contained in an amount of 3 to 15% by weight, more preferably 4 to 10% by weight, and it may be used as a polymer composition containing other desired components (pigment, plasticizer, etc.). Water and / or ethanol can be used as the solvent.

The pigment is used to protect the medicinal component from light or the like, or to impart aesthetics to the tablets or to classify the tablets. For example, titanium oxide, talc and the like can be used, but not limited to these. The film-forming polymer composition of the present invention preferably contains a pigment in an amount of 0.5 to 1
0% by weight, more preferably 1 to 5% by weight.

The coating is performed by a conventional coating method, for example, using a commercially available device so that the film thickness is 10 to 50 μm. In the examples of the present specification, film coating was performed using a laboratory scale doria coater (manufactured by Bowrec Co., Ltd.). still. Examples of active ingredients that can be formulated in this manner include various pharmaceuticals such as bromocriptine, pindolol, bobindolol, digoxin, metolazone, amlodipine.

Examples will be described below, but these examples are not intended to limit the present invention.

[0028]

[Examples and Test Examples] Example 1 A. The plain tablets of FIGS. 1, 3 and 4 were manufactured, and each was subjected to film coating, and the occurrence of troubles in the coating process was compared. FIG. 1 is a plain tablet of a preferred embodiment of the present invention already described, and FIGS. 3 and 4 are typical flat tablets of a conventionally known split tablet (upper punch: flat die with score line lower punch: flat punch). Type) and a lower punch flat type karate type (upper punch: V secant edge angle lower punch: flat type edge angle) (Unexamined Japanese Patent Publication No. 61-289027). In each figure, a, b,
And c represent the meanings described in FIG.

For each plain tablet, 97% by weight of an excipient of crystalline cellulose-anhydrous calcium hydrogen phosphate (2: 1 W / W) was prepared by a single-shot tableting machine KT-2 type (manufactured by Niei Seiko Co., Ltd.).
, Sodium carboxymethyl starch, 1% by weight of magnesium stearate, and prepared as a plain tablet having a diameter of 8 mm and a weight of 200 mg by a direct compression method.

The strength of the uncoated tablets measured by a tablet breaking strength measuring device (Toyama Sangyo Co., Ltd.) was adjusted to 7 to 8 kg.

B. HPMC as a coating film agent
6% by weight of TC-5, titanium oxide and talc as pigments, 20% by weight and 10% by weight of HPMC, respectively, were dissolved in a water / ethanol mixed solution to prepare a coating solution. Using a laboratory scale Doria Coater 500 (manufactured by Bowrec Co., Ltd.), the uncoated tablets were film-coated so that the coating solution had a film thickness of 30 to 50 μm. In this example, the following two types of TC, E type and R type, were used.
-5 was used.

[0032]

[Table 1] Variety Viscosity Average degree of polymerization * E 2.5-3.5 65 R 5.2-7.0 160 * Weight average degree of polymerization by GPC method (corrected by light scattering method)

Test Example 1 Tablet Shape and Coating Trab
The relationship between the incidence tablet shapes and various film coating troubles Le shown in Table 2. As can be seen from Table 2, the lower punch curved type karate type split tablet of the present invention (FIG. 1) is a conventional flat type split tablet (FIG. 3) and the lower punch flat type karate type split tablet (FIG. 4).
There was no film coating trouble such as twinning. In the case of the flat type, when film coating is applied, coating problems such as twinning, core erosion and edge chipping during film coating occur (Table 2), and further there is a problem in divisibility during division (Table 3). The lower pestle type karate type was slightly hard to break (Table 3), and coating problems such as twinning and core erosion were observed (Table 2).

[0034]

[Table 2]Table 2 Tablet shapes and incidence of coating problems  Conventional Conventional The present invention Flat type lower punch Flat type lower punchKarate type Karate type Twinning 78% 30% 0% Core erosion 6% 4% 0% Edge chipping 1% 0% 0% Uncoated tablet hardness: 7-8kg Tablet breaking strength tester (Toyama
Sangyo Co., Ltd.) Tablet diameter: 8 mm φ

Test Example 2 HPMC variety and blending ratio
Occurrence rate of coating troubles An uncoated tablet is manufactured using the lower punched type karate type (Fig. 1) of the present invention,
Film coating was performed according to Example 1.B using HPMC R-type and E-type blended in various proportions. As a result of examining the occurrence rates of various coating troubles (twinning, core erosion, edge chipping), coating troubles did not occur at all in any mixing ratio. Hardness of plain tablet: 6-7kg Tablet breaking strength measuring device (Toyama Sangyo Co., Ltd.) Tablet diameter: 8mmφ

From the results of Test Examples 1 and 2, when the tablet shape is the lower punched type of the present invention and HPMC is used as a coating film agent (regardless of the type of HPMC), troubles during film coating occur. It turned out to be resolved.

Test Example 3 Tablet Shape and Dividability A plain tablet was produced in the tablet shape shown in FIGS. 1, 3 and 4.
Film coating was performed according to Example 1.B using HPMC TC-5. The splittable tablets coated with a film were tested for splittability (breakability at splitting, bending strength). The results are shown in Table 3. As can be seen from Table 3, in the case of the karate type divided tablets such as the lower punched type karate type divided tablet (Fig. 1) and the lower punch flat type karate type divided tablet (Fig. 4) of the present invention, flat type division Compared with the tablet (Fig. 3), it was easy to divide and the bending strength showed a small value.

[0038]

[Table 3]Table 3 Tablet shape and severability  Conventional Conventional The present invention Flat type lower punch Flat type lower punchKarate type Karate type Difficult to crack when splitting Somewhat easy to crackEasy to break Hard to break Bending strength 6.4Kg 5.1Kg 3.6Kg Uncoated tablet hardness: 7-8kg Tablet breaking strength measuring device (Toyama
Sangyo Co., Ltd.) Tablet diameter: 8 mm φ Bending strength measurement: Tablet with the scored line down
When placed on a table and divided so that the score line opens from the pressure head
Was used as the bending strength. Tablet breaking strength measuring instrument (from Toyama
Industry

Test Example 4 HPMC variety and blending ratio and minutes
Splitting Manufacture an uncoated tablet with the lower rod-shaped Karate type (Fig. 1) of the present invention,
A coating solution was prepared by using R type and E type of HPMC with changing the compounding ratio as shown in Tables 4 and 5. Film coating was performed according to Example 1.B and its splittability was tested. Table 4 shows the results of unpackaged products, and Table 5 shows the results of PTP (vinyl chloride / vinylidene chloride composite sheet thickness: 300 μm) blister-packed products divided from the top. The blister packaging is a sheet-shaped packaging form in which a thermoplastic film is heated, a pocket or a pocket is formed by compressed air, a tablet or a capsule is put in the pocket, and the aluminum foil is heated and pressed.

[0040]

[Table 4]Table 4 HPMC varieties, blending ratios and partitioning properties (unpackaged products)  R R / E R / E R / E E(2: 1 W / W) (1: 1 W / W) (1: 2 W / W) When splitting Easy to crack Easy to crack Easy to crack Easy to crack Easy to crackFragility Bending strength 2.8Kg 2.8Kg 2.8Kg 2.8Kg 2.2Kg Appeared when divided Approved Approved Admitted Slightly not Admitted Film adhered Approval Uncoated tablet hardness: 6-7kg Tablet breaking strength measuring device (Toyama
Sangyo Co., Ltd.) Tablet diameter: 8 mm φ Bending strength measurement: Tablet with the scored line down
When placed on a table and divided so that the score line opens from the pressure head
Was used as the bending strength. Tablet breaking strength measuring instrument (from Toyama
Industry

[0041]

[Table 5]Table 5 HPMC varieties, blending ratios and partitioning properties (PTP packaged products)  R R / E R / E R / E E(2: 1 W / W) (1: 1 W / W) (1: 2 W / W) Difficult to split when splitting Difficult to split Difficult to split Almost easy to splitEasy to break Easy to break Bending strength 3.5Kg 3.3Kg 3.3Kg 3.0Kg 2.6Kg Allowed when dividing Allowed Allowed Allowed Slightly not allowed Film adhered Allowed The bending strength is divided by opening the score line from the top of the PTP package.
And measured. The hardness and tablet diameter of uncoated tablets are the same as in Table 4.

As described above, the film-coated tablets film-coated with the coating liquid in which the HPLC type and the compounding ratio were changed had no problem in the ease of division in any sample in the unpackaged form (Table 4). ), When PTP packaging is applied, E type HPMC is 2
It was found that there was a slight problem in separability unless it was blended at / 3 or more (Table 5).

Further, in both unpackaged and PTP packaged, the tensile strength of the film was reduced by incorporating a low molecular weight polymer such as E type HPMC. As a result, it becomes possible to integrally divide the uncoated tablet and the film at the time of division, and the appearance and shape of the divided surface are improved, and the problem of film adhesion is solved.

Test Example 5 Measurement of Physical Properties of Film A casting film was prepared by using the coating solution of Example 1.B in which the E type and / or the R type of TC-5 was used as HPMC in the ratio shown in each table. After the preparation, the tensile strength and elongation of the film were measured by Shimadzu Autograph (film thickness: 50 μm). The results are shown in Table 6.

[0045]

[Table 6]Table 6 Tensile strength and elongation of film  HPMC varieties RR / ER / ER / EEAnd blending ratio (2: 1 W / W) (1: 1 W / W) (1: 2 W / W) Tensile strength 511 512 452 401 407(Kg / cm ² ) Elongation rate 5.1 4.5 3.8 3.8 2.5 2.0(%) Moisture 3.1 3.5 3.5 3.4 3.3 3.7(%)  Test method: Shimadzu Autograph (DSS-10T-S type),
Film thickness 50 ± 5 μm 25 ° C., 52% RH After left for 2 days (temperature control), 25
℃, 50% RH measured in a constant temperature room

From Table 6 and the results of Test Examples 2 to 4,
For the production of a film-coated split tablet, which is easy to split and can be split together with a tablet whose film is split in half when splitting, when the coating is formed into a film with a thickness of 50 μm, 300 Kg / Cm ²
To 450 Kg / cm ² tensile strength and 1.5%
It has been found that it is preferable to have a physical property with an elongation of 0.1 to 3.5%.

Test Example 6 Weight Deviation of Divided Tablets An uncoated tablet was manufactured by the lower punched type karate type of the present invention (FIG. 1),
Film coating was performed according to Example 1.B using E-type HPMC. Using the coated tablets, a weight deviation test was carried out before division (base tablet) and after division (half tablet).

As a result, as shown in Table 7, a good value was obtained for the weight deviation after division, and it became clear that the present divided tablets can be divided uniformly.

[0049]

[Table 7] Table 7 Weight deviation of divided tablets (n = 20) Raw tablets Half tablets Average ± standard deviation Coefficient of variation Mean ± standard deviation Coefficient of variation 206.3 ± 1.1 0.5 103.2 ± 2.1 2 .0

[0050]

EFFECTS OF THE INVENTION By devising the shape of a film-coated split tablet, a split tablet that can prevent troubles during coating and can be split easily was obtained.

Further, if desired, a cellulose ether polymer such as HPMC (preferably containing 65% or more of a low molecular weight polymer such as HPMC-E type in the total amount used) is used as a film forming agent for film coating. , Almost no film adhesion was observed, and PT
Even in the P-packaged product, a divided tablet which can be easily divided by pressing the PTP with a finger was obtained. This divided tablet showed a small change in tablet weight due to division and showed good dividing property.

[Brief description of drawings]

FIG. 1 shows an embodiment of a tablet-shaped lower punch curved type of the present invention (upper punch: V secant edge angle lower punch: R edge angle). R is the radius of curvature of the lower surface, r is the radius of curvature of the upper surface, and R> r. a is a bottom view, b is a top view, and c is a side view.

FIG. 2 shows one aspect of a tablet-shaped lower punch curved type karate type of the present invention (upper punch: V secant edge angle lower punch: R edge angle). R represents the radius of curvature of the lower surface, and the upper surface represents a flat slope. a is a bottom view, b is a top view, and c is a side view.

FIG. 3 is a known tablet shape of a flat type (upper punch:
Flat type with score line Lower punch: Flat type. a is a bottom view, b is a top view, and c is a side view.

FIG. 4 shows a known tablet-shaped lower punch flat type karate type (upper punch: V secant edge angle lower punch: flat type edge angle). a is a bottom view, b is a top view, and c is a side view.

Claims (7)

[Claims] 1. A disc-shaped uncoated tablet having a dividing line formed of at least one groove for facilitating the division of the tablet on the upper surface and / or the lower surface, the upper surface of which faces the dividing line from opposite edges. Gradually dent the bottom surface and gradually swell the bottom surface from the peripheral part to the central part, provided that the central part is thinner than the peripheral part and is film-coated. . 2. The tablet according to claim 1, wherein the concave upper surface and the raised lower surface each form a curved surface, and the radius of curvature of the upper surface is smaller than the radius of curvature of the lower surface. 3. The tablet according to claim 1, which has a circular or elliptical outline when viewed from above and below. 4. The tablet according to claim 3, wherein the circular diameter is in the range of 3 mm to 12 mm. 5. 250 Kg / cm ² to 450 when the coating is formed on a 50 μm thick film.
The tablet according to any one of claims 1 to 4, which has a tensile strength of Kg / cm ² and a physical property of an elongation of 1% to 4%. 6. The tablet according to any one of claims 1 to 5, wherein the film coating is formed from a film-forming polymer containing a cellulose ether polymer and optionally a pigment. 7. The tablet according to claim 6, wherein the cellulose ether polymer is hydroxypropyl methylcellulose.