Film for wrapping tablet

Abstract

To provide a film which includes a polymer of at least one of hypromellose and hydroxypropyl cellulose and allows a cup part for housing a molded body containing a drug component to be formed at a lower molding temperature.SOLUTION: A film including a polymer of at least one of hypromellose and hydroxypropyl cellulose and at least one additive selected from a group of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol, and sugar alcohols is disclosed. The film is used for wrapping molded bodies containing a drug component.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present disclosure relates to a film for wrapping tablets, a method for manufacturing tablets, tablets, and a method for improving the shape retention and / or chemical stability of tablets.

Background Art

[0002] In manufacturing pharmaceutical formulations for oral administration, as one of the methods used, additives such as excipients, binders, or disintegrants are added to the active ingredient, and the homogenized powder is compression-molded. Then, considering quality deterioration due to light or patient use, film coating is applied to form tablets. However, depending on the type of active ingredient, it may be difficult to tablet a tablet having sufficient hardness for distribution in the market or for prescription and dosing. The quality of the tablet may also be impaired because a part of the molded body is damaged by the physical impact during film coating. In addition, the solvent used during film coating may affect the stability of the active ingredient.

[0003] Examples of pharmaceutical formulations in forms other than tablets include capsules. Capsules are manufactured, for example, by filling a pre-formed capsule with a powder of an active ingredient and sealing it. However, since capsules generally exist only in standard uniform shapes and standardized sizes, it is difficult to give a capsule a characteristic appearance like a tablet. In addition, since there are voids in the capsule filled with powder, the amount of powder that can be filled in the capsule decreases, and the capsule becomes larger. Furthermore, some capsules are easy to open, and in that case, the contents of the capsule can be replaced. On the other hand, there is a pharmaceutical formulation manufactured by filling a powder filled in a cup formed of a thermoplastic film, compressing it with a pestle, and then sealing it. However, in the powder filling of these pharmaceutical formulations, since the mechanism of a capsule filling machine is used, it is difficult to precisely control the amount of filled powder.

[0004] As a means for solving such problems, a molded body containing a medicinal ingredient of an orally administered preparation may be wrapped with a thermoplastic sheet or film. In order to produce a preparation in such a form, a method has been considered in which a cup portion having an opening is formed by pressing a mold against a thermoplastic sheet or film, a molded body containing a medicinal ingredient is inserted into the cup portion, and then a lid portion for sealing the opening of the cup portion is formed (Patent Documents 1 to 3).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0006] By using a film containing hypromellose or hydroxypropyl cellulose, it is possible to wrap a molded body containing a medicinal ingredient while ensuring the elution property of the medicinal ingredient. However, a film containing hypromellose or hydroxypropyl cellulose requires a relatively high molding temperature in order to form a cup portion for accommodating the molded body containing the medicinal ingredient.

[0007] Therefore, one aspect of the present disclosure relates to a film containing at least one of hypromellose or hydroxypropyl cellulose, which can form a cup portion for accommodating a molded body containing a medicinal ingredient at a lower molding temperature.

Means for Solving the Problems

[0008] One aspect of the present disclosure provides a film used for wrapping a molded body containing a medicinal ingredient, the film comprising at least one polymer selected from hypromellose or hydroxypropyl cellulose, and at least one additive selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol, and sugar alcohol.

[0009] Another aspect of the present disclosure provides a method for manufacturing a tablet, which includes forming a cup portion having an opening by pressing the above-mentioned film according to one aspect of the present disclosure, which has been heated, against a mold; inserting a molded body containing a medicinal ingredient into the cup portion; and forming a lid portion for closing the opening with a film for the lid portion, thereby wrapping the molded body with the lid portion and the cup portion.

[0010] Yet another aspect of the present disclosure provides a tablet including a molded body containing a medicinal ingredient, a cup portion that houses the molded body and has an opening, and a lid portion that closes the opening. The cup portion is the above-mentioned film according to one aspect of the present disclosure.

[0011] Still another aspect of the present disclosure provides a method for improving the shape retention and / or chemical stability of a tablet, which includes wrapping a molded body containing a medicinal ingredient with one or more films including the above-mentioned film according to one aspect of the present disclosure.

Advantages of the Invention

[0012] According to one aspect of the present disclosure, there is provided a film that contains at least one polymer selected from hypromellose or hydroxypropyl cellulose and can form a cup portion for housing a molded body containing a medicinal ingredient at a lower molding temperature.

Brief Description of the Drawings

[0013]

Figure 1

Figure 2

Figure 3

Mode for Carrying Out the Invention

[0014] Hereinafter, some embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

[0015] FIGS. 1 and 2 are schematic views showing an example of a method for manufacturing a tablet. The method shown in FIGS. 1 and 2 includes: preparing a film 1 for cup part as shown in (a); forming a cup part 10 having an opening by pressing the heated film 1 for cup part against a mold 30 as shown in (b) and (c); removing a remaining part 1C other than the cup part 10 of the film 1 for cup part so that a part thereof remains as shown in (d); inserting a granular molded body 5 containing a medicinal ingredient into the cup part 10 as shown in (e); removing the remaining part 1C other than the cup part 10 of the film 1 for cup part as shown in (f); forming a lid part 20 for closing the opening of the cup part 10 with a film 2 for lid part, thereby wrapping the molded body 5 with the lid part 20 and the cup part 10 as shown in (g); and removing a remaining part 2C other than the lid part 20 of the film 2 for lid part as shown in (h) in this order. Here, "wrapping the molded body" means that the molded body is enclosed in one or more films.

[0016] The film 1 for cup part according to one embodiment is a single-layer film containing at least one polymer of hypromellose or hydroxypropyl cellulose and an additive.

[0017] The additive is at least one selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol, and sugar alcohol. The molecular weight of the polyethylene glycol may be 10,000 or less from the viewpoint of the moldability of the film 1 for the cup part, etc. The sugar alcohol may be, for example, sorbitol, erythritol, or xylitol.

[0018] The additive may be at least one selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, and polyethylene glycol, or the group consisting of triethyl citrate and triacetin.

[0019] The content of the additive may be, for example, 5 to 30% by mass, 5 to 20% by mass, or 5 to 15% by mass based on the total amount of the polymer and the additive. When the content of the additive is 30% by mass or less, a film 1 for the cup part having good moldability, hardly generating wrinkles, and excellent in handleability can be easily obtained.

[0020] From the viewpoint of handleability, etc., the tensile elastic modulus of the film 1 for the cup part may be 800 MPa or more, or 900 MPa or more. The upper limit of the tensile elastic modulus of the film 1 for the cup part is not particularly limited, but is, for example, about 2300 MPa. The method for measuring the tensile elastic modulus will be described in the examples below.

[0021] The film 1 for the cup part may further contain a pigment. The film 1 for the cup part containing a pigment can give a colored tablet. The pigment may be, for example, an inorganic pigment such as titanium oxide, iron sesquioxide, yellow iron sesquioxide, a synthetic tar pigment, or a combination thereof. The content of the pigment (especially an inorganic pigment) may be, for example, 30% by mass or less based on the total amount of the polymer and the additive.

[0022] In addition to the polymers, additives, and pigments exemplified above, the film 1 for the cup portion may further contain other components. Examples of other components include flavoring agents. The content of other components may be 10% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less based on the mass of the film 1 for the cup portion.

[0023] The thickness of the film 1 for the cup portion may be, for example, 40 to 80 μm, or 20 to 100 μm.

[0024] The film for the cup portion is not limited to a film composed only of the single-layer film 1 for the cup portion as shown in the example of FIG. 1. For example, the film for the cup portion may have a base film containing the above-described polymer and additive, and an adhesive layer provided on the base film. When the adhesive layer is provided, the cup portion 10 and the lid portion 20 can be joined more firmly. The adhesive layer may be, for example, a layer containing copovidone, methacrylic acid copolymer LD, ethyl acrylate-methyl methacrylate copolymer, polyvinylpyrrolidone, or aminoalkyl methacrylate copolymer E.

[0025] The film 1 for the cup portion can be obtained, for example, by applying a coating liquid containing a polymer, an additive, and other components added as necessary, and water, to a base material having a smooth flat surface such as a glass plate, and drying the coating film.

[0026] Press the heated film 1 for the cup part against the mold 30, and by applying a negative pressure to the gap between the film 1 for the cup part and the mold 30, a cup part 10 is formed, which consists of a bottom part 1A and a wall part 1B extending from the periphery of the bottom part 1A and has an opening formed by the end of the wall part 1B. To press the mold 30 against the film 1 for the cup part, the mold 30 may be moved toward the fixed film 1 for the cup part, or the film 1 for the cup part may be moved toward the fixed mold 30. When the mold 30 is separated from the film 1 for the cup part, usually, the remaining part 1C of the film 1 for the cup part other than the cup part 10 remains to some extent around the cup part 10. The shape and size of the cup part 10 are adjusted so that the molded body 5 can be accommodated. The bottom part 1A may be curved as shown or may be planar. The maximum value of the depth of the cup part 10 (the depth from the remaining part 1C) may be, for example, 8 mm or less. The maximum width of the cup part 10 (the maximum value of the distance between the inner surfaces of the cup part 10 when viewed from the depth direction of the cup part 10) may be, for example, 16 mm or less.

[0027] The temperature of the film 1 for the cup part (molding temperature) pressed against the mold 30 is a temperature adjusted so that the cup part 10 of a desired shape is appropriately formed. For example, the temperature of the film 1 for the cup part to be molded is 100 to 180 °C, or a temperature at which it becomes 120 to 160 °C. The time for pressing the mold 30 against the film 1 for the cup part may be within a range that does not affect the normal formation of the film.

[0028] After the cup part 10 is formed, most of the remaining part 1C around the cup part 10 is removed. For this purpose, for example, the film 1 for the cup part may be cut along the opening of the cup part 10 by irradiation with laser light.

[0029] Subsequently, a molded body 5 containing a medicinal ingredient is inserted into the cup portion 10. The molded body 5 can be formed, for example, by compression molding of a powder containing a medicinal ingredient and other components added as necessary. The molded body may have a score line. Examples of components other than the medicinal ingredient include excipients, binders, disintegrants, lubricants, stabilizers, and preservatives. The maximum width of the molded body 5 is usually about the same as the maximum width of the cup portion 10.

[0030] After the molded body 5 is inserted into the cup portion 10, the remaining portion 1C is removed by a method such as irradiation with a laser beam.

[0031] The heated film 2 for the lid portion is pressed against the surface of the cup portion 10 into which the molded body 5 is inserted and on which the molded body 5 is exposed. By applying a negative pressure to the resulting gap between the film 2 for the lid portion and the cup portion 10, a lid portion is formed and the film 2 for the lid portion is joined to the cup portion 10. The entire surface of the molded body 5 is covered by the lid portion 20, which consists of a ceiling portion 2A covering a part of the surface of the molded body 5 and a wall portion 2B extending from the periphery thereof, and the cup portion 10. In other words, the molded body 5 is wrapped by the lid portion 20 and the cup portion 10.

[0032] The temperature of the film 2 for the lid portion (molding temperature) pressed against the cup portion 10 into which the molded body 5 is inserted is adjusted so that a lid portion 20 having a desired shape is appropriately formed. For example, the molding temperature may be 100 to 180°C, or 120 to 160°C.

[0033] The film 2 for the lid portion is a thermoplastic film and may be, for example, the same film as the film 1 for the cup portion. Since the inner surface of the wall portion 2B of the lid portion 20 and the outer surface of the wall portion 1B of the cup portion 10 are adhered, the lid portion 20 (film 2 for the lid portion) may have a base film similar to the film 1 for the cup portion and an adhesive layer provided on the inner surface of the base film.

[0034] After the lid portion 20 is formed, the remaining portion 2C of the film 2 for the lid portion other than the lid portion 20 is removed by a method such as irradiation with a laser beam.

[0035] After that, if a treatment such as heat shrinkage is necessary, a tablet 50 is obtained, which is composed of a molded body 5, a cup portion 10 that houses the molded body 5, and a lid portion 20 that is joined to the cup portion 10 so that the molded body 5 is enclosed.

[0036] By wrapping the molded body containing the medicinal ingredient with two films composed of the film 1 for the cup portion and the film 2 for the lid portion, even when the shape retention such as the shape preservability of the molded body and the anti-friction strength, or the chemical stability of the molded body is insufficient, a tablet that can be stably handled can be obtained. Therefore, the film according to the present embodiment can also be used to improve the shape retention and / or chemical stability of an existing tablet having a molded body containing a medicinal ingredient.

Example

[0037] Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

[0038] 1. Raw materials Hypromellose (Hydroxypropylmethylcellulose) · TC-5S (Viscosity of 2% aqueous solution (20 °C): 15 mPa·s, Shin-Etsu Chemical Co., Ltd.) · TC-5R (Viscosity of 2% aqueous solution (20 °C): 6 mPa·s, Shin-Etsu Chemical Co., Ltd.) · TC-5M (Viscosity of 2% aqueous solution (20 °C): 4.5 mPa·s, Shin-Etsu Chemical Co., Ltd.) · TC-5E (Viscosity of 2% aqueous solution (20 °C): 3 mPa·s, Shin-Etsu Chemical Co., Ltd.) Hydroxypropylcellulose · HPC-M (Nippon Soda Co., Ltd.) Additives · Triethyl citrate (Morimura & Co., Ltd.) · Triacetin (Kanto Chemical Co., Inc.) · Propylene glycol (Kanto Chemical Co., Inc.) · PEG400 (Sanyo Chemical Industries, polyethylene glycol, average molecular weight 400) · Copovidone (copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate (mass ratio = 3:2), Ashland) · Polyvinylpyrrolidone (PVP K30, BASF) Dye (pigment) · Titanium oxide (Ishihara Sangyo)

[0039] 2. Preparation of Film According to the following procedure, a coating solution containing each raw material was prepared with the formulation described in Table 1, Table 2, or Table 3. The formulations described in each table are shown as ratios (mass %) based on the total amount of the polymer (hypromellose or hydroxypropyl cellulose) and the additives. First, the additives were dissolved in a mixed solvent of purified water / ethanol (volume ratio: 50 / 50). Hypromellose or hydroxypropyl cellulose was dissolved in the resulting aqueous solution to obtain a coating solution for film formation. The coating solution was degassed under vacuum and then coated on a glass plate with a certain thickness using an electric film applicator. The coating film was air-dried for one day and night to form a film with a thickness of 60 μm. Films with a thickness of 40 μm or 80 μm were also prepared using the coating solutions of Formulation 2 and Formulation 3.

[0040] 3. Evaluation 3-1. Tensile Test Strip-shaped test pieces with a width of 10 mm and a length of 50 mm were cut out from each film. After leaving the test pieces in an environment of 25°C and 60% RH for 1 hour, a tensile test was performed using an EZ-test (manufactured by Shimadzu Corporation). The distance between the grips was 30 mm, and the test speed was 10 mm / min.

[0041] 3-2. Formability (Formable Temperature) A 5 cm square film for evaluation was cut out from the produced film. The evaluation film was left for 1 hour in an environment of 25°C and 60% RH. Next, using a wrapping preparation manufacturing apparatus equipped with a heater for heating the film, in accordance with the manufacturing method of wrapping tablets described in the form for carrying out the invention in International Publication No. 2018 / 074261, the film was pressed against a mold having a cylindrical portion with an inner diameter of 7.5 mm, and a cup portion was formed by applying a negative pressure to the gap between the film and the mold. A molding test was conducted while changing the set temperature of the heater device for heating the film, and the formed cup portion was visually observed. When a cup portion having a shape that beautifully reflected the wall surface of the cylindrical portion of the mold was formed, it was determined as "moldable", and when a cup portion having a shape that expanded beyond the inner diameter of the cylindrical portion of the mold was formed, it was determined as "non-moldable". FIG. 3 is a photograph showing an example of a cup portion formed by the molding test. Among FIG. 3, "1" is an example of "moldable", and "2" and "3" are examples of "non-moldable". Among the set temperatures of the apparatus at which a "moldable" cup portion was formed, the lowest temperature was recorded as the "moldable set temperature". For example, when the set temperature of the heater for heating the film was about 400°C, the temperature at the heater outlet was 305 - 310°C, the temperature near the upper surface of the film at that time was 230°C, and the temperature of the lower surface of the film at that time was at most 120°C.

[0042] 4. Results The evaluation results are shown in Tables 1 - 4. It was confirmed that films with formulations containing triethyl citrate, triacetin, propylene glycol, or polyethylene glycol as additives could appropriately form cup portions at lower molding temperatures compared to the film of formulation 0 without additives. In the case of formulation 6, although it was moldable at a heater set temperature of 245°C, wrinkles were observed in the cup portion.

[0043] [Table 1]

[0044] [Table 2]

[0045]

Table 3

[0046]

Table 4

Explanation of Symbols

[0047] 1…Film for cup part, 1A…Bottom part, 1B…Wall part, 1C…Remaining part, 2…Film for lid part, 2A…Ceiling part, 2B…Wall part, 2C…Remaining part, 5…Formed body, 10…Cup part, 20…Lid part, 30…Mold, 50…Tablet.

Claims

1. At least one polymer selected from the group consisting of hypromellose and hydroxypropyl cellulose; at least one additive selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol, and sugar alcohol; The film is used for wrapping a molded article containing a medicinal ingredient.

2. The film according to claim 1, wherein the content of the additive is 5 to 30% by mass based on the total amount of the polymer and the additive.

3. The film according to claim 1 or 2, wherein the film has a tensile modulus of elasticity of 800 MPa or more.

4. The film of any one of claims 1 to 3, wherein the film further comprises a dye.

5. The film of any one of claims 1 to 4, wherein the additive is triethyl citrate, triacetin, or a combination thereof.

6. The film according to any one of claims 1 to 5, comprising a substrate film containing the polymer and the additive, and an adhesive layer provided on the substrate film.

7. 7. The film according to claim 1, which is used to manufacture a tablet by a method comprising pressing the heated film against a mold to form a cup portion for inserting a molded body containing a medicinal ingredient.

8. 8. The film of claim 7, which is used to manufacture a tablet by a method further comprising removing a remainder of the film other than the cup portion.

9. forming a cup portion having an opening by pressing the heated film according to any one of claims 1 to 6 against a mold; Inserting a molded body containing a medicinal ingredient into the cup portion; forming a lid portion that closes the opening using a lid film, thereby wrapping the molded body with the lid portion and the cup portion; A method for producing a tablet comprising:

10. The method of claim 9, further comprising removing a remainder of the film other than the cup portion after the molded body is inserted into the cup portion.

11. A molded body containing a medicinal ingredient; A cup portion that accommodates the molded body and forms an opening; A lid portion that closes the opening; Equipped with the molded body is wrapped by the lid portion and the cup portion, The cup portion is the film according to any one of claims 1 to 6. tablet.

12. A method for improving the shape retention and / or chemical stability of a tablet, comprising wrapping a molded body containing an active ingredient with one or more films including the film according to any one of claims 1 to 6.

Images