Film having improved elution

Abstract

To provide a film for further improvement in the elution of medicinal ingredients, with respect to a tablet having a molded product containing medicinal ingredients wrapped in a film containing a water-soluble polymer such as hypromellose.SOLUTION: Disclosed is a film comprising: at least one first water-soluble polymer selected from the group consisting of hypromellose, hydroxypropyl cellulose, and polyvinyl alcohol; and a second water-soluble polymer containing a monomeric unit derived from N-vinyl-2-pyrrolidone. The film is used to wrap a molded product containing medicinal ingredients.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] The present disclosure relates to a film for improving elution properties, 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 preparations 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 tablets may be impaired because a part of the molded body is damaged by the physical impact during film coating. Also, the solvent used during film coating may affect the stability of the active ingredient.

[0003] Examples of pharmaceutical preparations 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 a fixed, uniform shape and standardized size, it is difficult to give capsules a characteristic appearance like that of tablets. Also, 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 easily opened, and in that case, the contents of the capsule can be replaced. On the other hand, there is a pharmaceutical preparation 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 preparations, 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 thermoplastic sheet or film against a mold, 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] One aspect of the present disclosure relates to a film for further improving the elution property of a medicinal ingredient, with respect to a tablet in which a molded body containing a medicinal ingredient is wrapped with a film containing a water-soluble polymer such as hypromellose.

Means for Solving the Problems

[0007] One aspect of the present disclosure provides a film containing one or more first water-soluble polymers selected from the group consisting of hypromellose, hydroxypropylcellulose, and polyvinyl alcohol, and a second water-soluble polymer containing a monomer unit derived from N-vinyl-2-pyrrolidone, which is used for wrapping a molded body containing a medicinal ingredient.

[0008] Another aspect of the present disclosure provides a method for manufacturing tablets, which includes wrapping a molded body containing a medicinal ingredient with one or more films including the film according to one aspect of the present disclosure.

[0009] Yet another aspect of the present disclosure provides a tablet including a molded body containing a medicinal ingredient and one or more films including the film according to one aspect of the present disclosure. The molded body is wrapped by the one or more films.

[0010] Still another aspect of the present disclosure provides a method for improving the shape retention and / or chemical stability of tablets, which includes wrapping a molded body containing a medicinal ingredient with one or more films including the film according to one aspect of the present disclosure.

Advantages of the Invention

[0011] According to one aspect of the present disclosure, there is provided a film for further improving the elution property of a medicinal ingredient with respect to a tablet in which a molded body containing the medicinal ingredient is wrapped with a film containing a water-soluble polymer such as hypromellose.

Brief Description of the Drawings

[0012]

Figure 1

Figure 2

Modes for Carrying Out the Invention

[0013] Hereinafter, some embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

[0014] Figures 1 and 2 are schematic diagrams showing an example of a method for manufacturing tablets. The method shown in Figures 1 and 2 includes: preparing a film 1 for cup parts as shown in (a); forming a cup part 10 with an opening by pressing the heated film 1 for cup parts against a mold 30 as shown in (b) and (c); removing the remaining part 1C of the film 1 for cup parts other than the cup part 10 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 of the film 1 for cup parts other than the cup part 10 as shown in (f); forming a lid part 20 for closing the opening of the cup part 10 with a film 2 for lid parts as shown in (g), thereby wrapping the molded body 5 with the lid part 20 and the cup part 10; and removing the remaining part 2C of the film 2 for lid parts other than the lid part 20 as shown in (h) in this order. Here, "wrapping the molded body" means that the molded body is enclosed in one or more films.

[0015] The film 2 for lid parts has a film containing one or more first water-soluble polymers selected from the group consisting of hypromellose, hydroxypropyl cellulose, and polyvinyl alcohol, and a second water-soluble polymer containing a monomer unit derived from N-vinyl-2-pyrrolidone. More specifically, the film 2 for lid parts illustrated in Figure 2 is a laminated film composed of a first film 21 containing a first water-soluble polymer and a second film 22 containing a second water-soluble polymer provided inside the first film 21.

[0016] The second water-soluble polymer can be, for example, copovidone, polyvinylpyrrolidone, or a combination thereof. The content of the second water-soluble polymer in the second film 22 may be 50 to 100% by mass, 60 to 100% by mass, 70 to 100% by mass, or 80 to 100% by mass based on the mass of the second film 22 from the viewpoint of improving elution properties.

[0017] The second film 22 may further contain at least one additive selected from the group consisting of triethyl citrate, triacetin, propylene glycol, ethylene glycol, polyethylene glycol, and sugar alcohol. These additives can contribute to improving the moldability of the film 2 for the lid portion. 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 in the second film 22 may be, for example, 30% by mass or less based on the total amount of the second water-soluble polymer and the additive. When the content of the additive is 30% by mass or less, a film 2 for the lid portion having good moldability, hardly generating wrinkles, and excellent in handleability can be easily obtained.

[0020] The thickness of the second film 22 may be 5 to 60 μm, 10 to 30 μm, or 15 to 25 μm. The ratio of the thickness of the second film to the thickness of the first film may be 0.1 to 0.8. When the thickness of the second film 22 is within these ranges, the elution property can be particularly effectively improved without significantly impairing the handleability of the film 2 for the lid portion.

[0021] From the viewpoint of improving the moldability of the film 2 for the lid portion, the first film 21 may further contain the above additive. The content of the additive in the first film 21 may be, for example, 30% by mass or less based on the total amount of the first water-soluble polymer and the additive. When the content of the additive is 30% by mass or less, a film 2 for the lid portion having good moldability, hardly generating wrinkles, and excellent in handleability can be easily obtained.

[0022] At least one of the first film 21 or the second film 22 may further contain a pigment. The film 2 for the lid portion containing the pigment can provide 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 in the first film 21 or the second film may be, for example, 30% by mass or less based on the total amount of the first water-soluble polymer or the second water-soluble polymer and the additive.

[0023] At least one of the first film 21 or the second film 22 may further contain other components in addition to the water-soluble polymers, additives, and pigments exemplified above. 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 first film 21 or the second film 22.

[0024] Instead of the laminated film as shown, the film 2 for the lid portion may be a single-layer film containing the first water-soluble polymer and the second water-soluble polymer. In that case, the content of the second water-soluble polymer in the single-layer film may be 5 to 30% by mass based on the total content of the first water-soluble polymer and the second water-soluble polymer.

[0025] The single-layer film as the film 2 for the lid portion may further contain the above-described additives. The content of the additive in the single-layer film may be 30% by mass or less based on the total amount of the first water-soluble polymer, the second water-soluble polymer, and the additive.

[0026] The single-layer film as the film 2 for the lid portion may further contain the above-described pigment. The content of the pigment in the single-layer film may be, for example, 30% by mass or less based on the total amount of the first water-soluble polymer, the second water-soluble polymer, and the additive.

[0027] The above single-layer film as the film 2 for the lid portion may further contain the above other components. The content of other component dyes in the single-layer film 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 single-layer film.

[0028] The thickness of the above single-layer film as the film 2 for the lid portion may be, for example, 20 to 100 μm, 40 to 80 μm, or 50 to 70 μm.

[0029] The film 2 for the lid portion may further have an adhesive layer provided on the second film 22 or on the above single-layer 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.

[0030] The film 2 for the lid portion (the first film 21 and the second film 22) can be obtained, for example, by applying a coating liquid containing a first water-soluble polymer or a second water-soluble polymer, other components added as necessary, and water to a substrate having a smooth flat portion such as a glass plate, and drying the coating film.

[0031] The film 1 for the cup portion is a film having a thermoplastic film. The film 1 for the cup portion may be, for example, the same film as the film 2 for the lid portion or the same film as the first film 21.

[0032] 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.

[0033] 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 the 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.

[0034] 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.

[0035] Subsequently, the molded body 5 containing the medicinal ingredient is inserted into the cup part 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. 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 part 10.

[0036] 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.

[0037] 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 gap between the resulting 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 lid portion 20, which is composed 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 cover the entire surface of the molded body 5. In other words, the molded body 5 is wrapped by the lid portion 20 and the cup portion 10.

[0038] The temperature (molding temperature) of the film 2 for the lid portion pressed against the cup portion 10 into which the molded body 5 is inserted is adjusted so that the 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.

[0039] 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.

[0040] Thereafter, if necessary, a process such as heat shrinkage is performed, whereby a tablet 50 is obtained, which is composed of the molded body 5, the cup portion 10 in which the molded body 5 is accommodated, and the lid portion 20 joined to the cup portion 10 so that the molded body 5 is enclosed.

[0041] The molded body containing the medicinal ingredient is wrapped by two films composed of the film for the cup part 1 and the film for the lid part 2, so that 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

[0042] Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

[0043] 1. Raw materials First water-soluble polymer · Hypromellose (hydroxypropyl methylcellulose): TC-5S (viscosity of 2% aqueous solution (20 °C): 15 mPa·s, Shin-Etsu Chemical Co., Ltd.) · Hydroxypropyl cellulose: HPC-M (Nippon Soda Co., Ltd.) Second water-soluble polymer · Copovidone: copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate (mass ratio = 3:2, Ashland) · Polyvinylpyrrolidone: PVP K12 (Ashland), PVP K17 (BASF), PVP K25 (Ashland), PVP K30 (BASF), PVP K90 (BASF) Additives · Triacetin (Kanto Chemical Co., Inc.) Dye (pigment) · Titanium oxide (Ishihara Sangyo Co., Ltd.)

[0044] 2. Preparation of tablets Comparative Example 1 A coating solution containing each raw material can be prepared according to the formulation described in Table 1. The formulation described in the table is shown as a ratio (mass%) based on the total amount of the raw materials. First, the additive was dissolved in a mixed solvent of purified water / ethanol (volume ratio: 50 / 50), and hypromellose and hydroxypropyl cellulose were dissolved in the resulting aqueous solution to obtain a coating solution for film formation. After degassing the coating solution under vacuum, it was coated on a glass plate with a certain thickness using an electric film applicator, and the coating film was air-dried for a whole day and night to form Film A1 with a film thickness of 80 μm. A mold having a cylindrical portion with an inner diameter of 7.5 mm was pressed against Film A1 produced by the same procedure as the above method using a wrapping preparation manufacturing apparatus equipped with a heater for heating the film in accordance with the manufacturing method of the wrapping tablet described in the form for carrying out the invention in International Publication No. 2018 / 074261, and a cup portion was formed by applying a negative pressure to the gap between the film and the mold. The set temperature of the heater device for heating the film was 390°C, the heater outlet temperature at that time 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. A molded body containing a test agent was inserted into the cup portion. The molded body was prepared by compression molding 160 mg of powder containing 20 mg of the agent at a pressure of 10 kN. The heated Film A1 was pressed against the cup portion into which the molded body was inserted. By applying a negative pressure to the resulting gap between Film A1 and the cup portion, a lid portion was formed and the lid portion and the cup portion were joined to obtain an evaluation tablet in which the molded body was wrapped by the lid portion and the cup portion.

[0045] Examples 1 - 3 An aqueous solution containing copovidone and triacetin at a mass ratio of 90:10 was prepared as a coating solution. This coating solution was applied to Film A1 prepared in the same manner as in Comparative Example 1, and the coating film was dried in a dryer at 50 °C for 20 minutes to obtain laminated films B1, B2, and B3 composed of Film A1 and a copovidone / triacetin film with a film thickness of 10 μm, 20 μm, or 50 μm. Evaluation tablets were prepared in the same procedure as in Comparative Example 1, except that the film for forming the lid portion was changed to laminated film B1, B2, or B3. Each laminated film was arranged with the copovidone / triacetin film on the inside of the tablet.

[0046] Examples 4 to 6 An aqueous solution containing polyvinylpyrrolidone (PVP K12, PVP K25, or PVP K30) and triacetin at a mass ratio of 90:10 was prepared as a coating solution. This coating solution was applied to Film A1 prepared in the same manner as in Comparative Example 1, and the coating film was dried in a dryer at 50 °C for 20 minutes to obtain laminated films B4, B5, and B6 composed of Film A1 and a polyvinylpyrrolidone / triacetin film with a film thickness of 10 μm. Evaluation tablets were prepared in the same procedure as in Comparative Example 1, except that the film for forming the lid portion was changed to laminated film B4, B5, or B6. Each laminated film was arranged with the copovidone / triacetin film on the inside of the tablet.

[0047] Comparative Example 2 An aqueous solution containing hypromellose (TC-5S) and triacetin at a mass ratio of 90:10 was prepared as a coating solution. Using the obtained coating solution, Film A2 with a film thickness of 60 μm was obtained in the same procedure as in Comparative Example 1. Evaluation tablets were prepared in the same procedure as in Comparative Example 1, except that the films for forming the cup portion and the lid portion were changed to Film A2.

[0048] Examples 7 to 10 An aqueous solution containing hypromellose (TC-5S) and copovidone or polyvinylpyrrolidone (PVP K17, PVP K30, or PVP K90) at a mass ratio of 90:10 was prepared as a coating solution. Using the obtained coating solution, films C1, C2, C3, and C4 with a film thickness of 60 μm were obtained by the same procedure as in Comparative Example 1. Tablets for evaluation were prepared by the same procedure as in Comparative Example 1, except that the films for forming the cup part and the lid part were changed to film C1, C2, C3, or C4.

[0049] 3. Dissolution test The dissolution test of the obtained tablets was carried out by the paddle method under the following conditions according to the Second Method of the Japanese Pharmacopoeia Dissolution Test Method. Test solution: Dissolution Test Second Solution Volume of test solution: 900 mL Temperature of test solution: 37 °C Paddle rotation speed: 50 rpm The dissolution rate 10 minutes after the start of the test was determined. The measurement results of the dissolution rate are shown in Tables 1 and 2. Each test in Table 1 was carried out with N = 6, and each test in Table 2 was carried out with N = 12. It was confirmed that tablets with improved dissolution properties of the medicinal ingredient could be obtained by wrapping the molded body with a film containing copovidone or polyvinylpyrrolidone as in each example.

[0050]

Table 1

[0051]

Table 2

Explanation of symbols

[0052] 1... Film for cup part, 1A... Bottom, 1B... Wall part, 1C... Remaining part, 2... Film for lid part, 2A... Ceiling part, 2B... Wall part, 2C... Remaining part, 3... Film, 5... Molded body, 10... Cup part, 20... Lid part, 21... First film, 22... Second film, 30... Mold, 50... Tablet.

Claims

1. one or more first water-soluble polymers selected from the group consisting of hypromellose, hydroxypropyl cellulose, and polyvinyl alcohol; a second water-soluble polymer comprising monomeric units derived from N-vinyl-2-pyrrolidone; The film is used for wrapping a molded article containing a medicinal ingredient.

2. The film of claim 1 , comprising a laminated film having a first film comprising the first water-soluble polymer and a second film comprising the second water-soluble polymer laminated onto the first film.

3. The film according to claim 2, wherein the content of the second water-soluble polymer in the second film is 50 to 100% by mass based on the mass of the second film.

4. The film of claim 2 or 3, wherein the ratio of the thickness of the second film to the thickness of the first film is from 0.1 to 0.

8.

5. The film of any one of claims 2 to 4, wherein at least one of the first film or the second film further comprises a dye.

6. The film according to any one of claims 2 to 5, further comprising an adhesive layer provided on the second film of the laminated film.

7. The film of claim 1 comprising a single layer of film comprising the first water-soluble polymer and the second water-soluble polymer.

8. The film according to claim 7, wherein the content of the second water-soluble polymer in the monolayer film is 5 to 30 mass% based on the total content of the first water-soluble polymer and the second water-soluble polymer.

9. 9. The film of claim 7 or 8, wherein the monolayer film further comprises a dye.

10. The film according to any one of claims 7 to 9, further comprising an adhesive layer provided on the single layer film.

11. A method for producing 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 10.

12. A molded body containing a medicinal ingredient; One or more films comprising the film according to any one of claims 1 to 10; Equipped with The molded body is wrapped with the one or more films. tablet.

13. 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 10.

Images