JP2002241275A - Oral solid preparation inhibiting sublimation of ingredient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral solid preparation which is excellent in productivity and inhibits the sublimation of a medicine, especially ibuprofen. SOLUTION: This oral solid preparation which inhibits the sublimation of an ingredient is characterized by containing the sublimating ingredient such as ibuprofen and being ground-coated with a saccharide.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an oral solid preparation in which sublimation of components is suppressed, and more particularly, to an oral solid preparation in which sublimation of a contained sublimable drug, particularly ibuprofen, is suppressed.

[0002]

2. Description of the Related Art There are various sublimable drugs among the main components of cold medicines. In a preparation containing such a drug, a sublimate may re-precipitate to form whisker-like crystals called whiskers, or to adhere to a storage container to cause clouding. As an example, there is a water droplet-like clouding phenomenon due to sublimation of caffeine whisker or ibuprofen which precipitates on the tablet surface. It is well known that caffeine whisker suppresses its generation by applying a film coating to tablets, but film coating is not sufficient for sublimation of ibuprofen. Ibuprofen is included in cold medicines etc. as an antipyretic analgesic.However, if a formulation containing ibuprofen is stored in a bottle package, sublimates of cloudy ibuprofen are generated inside the bottle after several days even at room temperature even at room temperature. Is observed. Although this phenomenon does not cause any problem in terms of quality, it is not desirable in appearance, and thus needs to be improved. However, this phenomenon cannot be suppressed by applying a normal aqueous film coating to uncoated tablets such as caffeine whiskers as a method of improving this effect, and dragees are not effective in suppressing the sublimation of ibuprofen. There are drawbacks, however, in that the size of the tablet is increased, the number of manufacturing steps is increased, and the cost is increased. JP-A-8-193027 and JP-A-8-333
No. 247 prevents sublimation by storing one or more substances selected from the group consisting of polyvinylpyrrolidone, magnesium oxide and sodium bicarbonate in a solid preparation containing sublimable ibuprofen in a closed system. And methods to prevent sublimation by storing the ibuprofen-containing solid preparation and the desiccant in a closed system, but these methods cannot completely suppress the fogging of the bottle, especially When the temperature is close to 40 ° C. in summer or the like, almost no effect is seen. Furthermore, even if a desiccant or the like is enclosed, a sufficient suppression effect cannot be obtained, which leads to an increase in cost. Japanese Patent No. 2841267 discloses a method of coating a granule with a water-insoluble polymer and further coating a saccharide. The main purpose of the method is to mask bitterness, and the improvement is achieved by a combination of a water-insoluble film and a saccharide. ing. Further, the description is only for granules, and does not apply to tablets.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide an oral solid preparation which is excellent in manufacturability and suppresses sublimation of contained sublimable drugs, in particular, ibuprofen.

[0004]

Means for Solving the Problems As a result of intensive studies, the present inventors have found that sublimation as described above can be suppressed by using a film tablet with a sugar underhang, and completed the present invention. Was. That is, the present invention

(1) An oral solid preparation containing a sublimable component and sublimated with a saccharide to suppress sublimation of the component, and (2) an underlayer weighing 100 parts by weight of uncoated tablets (3) oral solid preparation according to the above (1), wherein the oral solid preparation is 2 to 50 parts by weight with respect to (1),
The oral solid preparation according to the above (1), wherein the weight of the film coating is 2 to 10 parts by weight based on 100 parts by weight of the uncoated tablet, (5) any of the above (1) to (4), wherein the sublimable component is ibuprofen The oral solid preparation according to claim 1,
(6) A method for suppressing fogging of a storage container of an oral solid preparation containing a sublimable component, the method comprising subjecting the oral solid preparation to underling with a saccharide.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION In the present specification, "undergarment of saccharide" means that a layer of saccharide is formed between an uncoated tablet and an outer layer, and a substance containing a sublimable drug such as ibuprofen as an active ingredient. A tablet is manufactured and sprayed with a solution of the sugar dissolved or dispersed therein. In addition, the outer layer means that a film coating or other coating is applied on a saccharide layer as an underlayer.

The sublimable drug used as an active ingredient of the oral solid preparation of the present invention includes ibuprofen,
These may be used alone or in combination of two or more. Although not limited, the present invention is particularly effective for suppressing sublimation of ibuprofen. The uncoated tablet of the present invention can be produced by a method known per se, and the components other than the active ingredient to be formulated, and the formulation amount of each formulation component is not particularly limited, and depends on the desired use, performance, and the like. Can be selected as appropriate.

Examples of the saccharide used include monosaccharides, disaccharides, oligosaccharides and sugar alcohols thereof, and purified sucrose, lactose, glucose, trehalose, sugar alcohols and the like are desirable. Preferred sugar alcohols include, for example, erythritol, xylitol, sorbitol, D-mannitol, powdered reduced maltose aqueous candy, and the like. These can be used alone or as a mixture of two or more, and can also be used as a mixture with an excipient or the like. The weight of the undercoat layer is usually 1 to 100 parts by weight, preferably 2 to 50 parts by weight, based on 100 parts by weight of the uncoated tablet.

The oral solid preparation of the present invention is usually applied with a film coating on an undergarment by a method known per se. Examples of the film-forming material used for film coating include ethyl cellulose [eg, Aquacoat (trade name, Asahi Kasei Kogyo Co., Ltd.)], carboxymethyl cellulose, carmellose, carmellose calcium, carmellose sodium, low-substituted hydroxypropyl cellulose. And hydroxypropylmethylcellulose [eg, hydroxypropylmethylcellulose 2208, hydroxypropylmethylcellulose 2906, hydroxypropylmethylcellulose 2910, etc.], hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate, methylcellulose and the like. These can be coated alone or in a mixture with the above-mentioned excipients, plasticizers and the like (eg, titanium oxide, lactose, polyethylene glycol, etc.), or can be coated in several different compounds. When a film coating is applied as the outer layer, there is also an advantage that the impact strength is superior to the case where no film coating is applied. The weight of the outer layer is usually 2 to 10 parts by weight based on 100 parts by weight of the uncoated tablet.

[0010] Thus, the oral solid preparation of the present invention is an oral solid preparation in which the generation of whiskers due to the sublimation of sublimable components and the fogging phenomenon of the heat insulating container are suppressed, and it can be used as a cold medicine or the like depending on the active ingredients. .

[0011]

EXAMPLES Examples, comparative examples, and experimental examples will be described below.
The present invention will be described in more detail, but the present invention is not limited thereto. Example 1 According to the formulation shown in Table 1, each of Group I and Group P was sprayed with a hydroxypropylcellulose solution using a fluidized bed granulator (FD-3SN, manufactured by Powrex) and granulated by a conventional method. And these two types of granulated powder (I group 1717.5)
g and P group 352.5 g) were sized, respectively, and 254 g of Avicel PH101, 96 g of disintegrant Akdizol, and 10 g of magnesium stearate as a lubricant.
g added and mixed (tumbler mixer: Showa Chemical Machinery Co., Ltd.)
TM-15), and then a plain tablet of 270 mg / tablet was manufactured using a rotary tableting machine (manufactured by Kikusui Seisakusho, Collect 19K). The uncoated tablet is a purified sucrose aqueous solution (40w /
w%) and sprayed (increased weight: 15 mg / tablet) (High Coater 20, manufactured by Freund Corporation) to form a sugar layer on the tablet surface. Thereafter, a film coating solution using hydroxypropyl methylcellulose, titanium oxide and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight 8 mg /
Tablets) to give film-coated tablets.

[0012]

[Table 1]

Example 2 An unpurified sucrose aqueous solution (40 w / w) was added to the uncoated tablets prepared in Example 1.
%) And sprayed (increased weight: 25 mg / tablet) (High Coater 20) to form a saccharide layer. Thereafter, a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight: 8 mg / tablet) to obtain a film-coated tablet.

Example 3 A lactose dispersion (20 w / w%) was sprayed onto the uncoated tablet prepared in Example 1 to carry out underlaying (increased weight: 20 mg / tablet) (Hicoater 20) to form a saccharide layer. did. Thereafter, a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight: 8 mg / tablet) to obtain a film-coated tablet.

Example 4 The uncoated tablet prepared in Example 1 was added to an erythritol aqueous solution (30w).
/ W%) and sprayed (increased weight: 15 mg / tablet) (Hicoater 20) to form a saccharide layer. Thereafter, a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight: 8 mg / tablet) to obtain a film-coated tablet.

Example 5 According to the formulation shown in Table 2, each of the groups I and P was sprayed with a hydroxypropylcellulose solution using a fluidized bed granulator (FD-3SN, manufactured by Powrex) and granulated by a conventional method. did. Then, these two types of granulated powder (1369.0 group I)
g and P group, 1056.0 g), respectively, and 5 g of magnesium stearate as a lubricant was added and mixed (tumbler mixer: TM-15 type, manufactured by Showa Chemical Machinery Co., Ltd.), and then rotary punching was performed. An uncoated tablet of 270 mg / tablet was manufactured using a tablet machine (Kikusui Seisakusho, Collect 19K). The uncoated tablet was sprayed with an aqueous solution of purified sucrose (40 w / w%) to underlay (increased weight: 15 mg / tablet) (High Coater 20, manufactured by Freund Corporation) to form a saccharide layer on the tablet surface. Then hydroxypropyl methylcellulose, titanium oxide, polyethylene glycol (75:10:15)
Was spray-coated to obtain a film-coated tablet (increased weight: 8 mg / tablet).

[0017]

[Table 2]

Example 6 The uncoated tablet prepared in Example 5 was sprayed with a purified sucrose + talc dispersion solution (4: 1, 50 w / w%) to give an undercoat (increased weight: 15 mg / tablet) (Hicoater 20). ), A saccharide layer was formed. Then, hydroxypropyl methylcellulose, titanium oxide, polyethylene glycol (75:
10:15) to perform film coating (increased weight: 8 mg / tablet) to obtain film-coated tablets.

Example 7 A plain sucrose aqueous solution (40 w / w) was added to the uncoated tablets prepared in Example 5.
%) And sprayed (increased weight: 4 mg / tablet) (Hicoater 20) to form a saccharide layer. afterwards,
Spraying a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) to perform film coating (increased weight: 8 mg / tablet) to obtain a film-coated tablet.

Example 8 A purified sucrose aqueous solution (40 w / w) was added to the uncoated tablets prepared in Example 5.
%) And sprayed (increased weight: 15 mg / tablet) (Hicoater 20) to form a saccharide layer. Thereafter, a film coating solution using hydroxypropylmethylcellulose, titanium oxide, and lactose (45:15:40) is sprayed to perform film coating (increased weight 8).
mg / tablet) to give a film-coated tablet.

Example 9 According to the formulation shown in Table 3, each of the groups I and M was sprayed with a hydroxypropylcellulose solution using a fluidized bed granulator (FD-3SN, manufactured by Powrex) and granulated by a conventional method. did. And these two types of granulated powder (I group 1300.0
g and 980.0 g of the P group) were sized, 60 g of Avicel PH101 and 5 g of a disintegrant, Acdizol.
2.8 g and 7.2 g of magnesium stearate as a lubricant were added and mixed (tumbler mixer: TM-15 type, manufactured by Showa Chemical Machinery Co., Ltd.), and then a rotary tableting machine (Kikusui Seisakusho, Collect) 400mg at 19K)
/ Tablets were manufactured. Add an aqueous purified sugar solution (40
(w / w%) and sprayed on it (increased weight: 15 mg / tablet)
(High Coater 20, manufactured by Freund Corporation) to form a saccharide layer on the tablet surface. Thereafter, a film coating liquid using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) is sprayed to perform film coating (increased weight 8 mg).
/ Tablet) to obtain a film-coated tablet.

[0022]

[Table 3]

EXAMPLE 10 A purified sucrose aqueous solution (40 w / w) was added to the uncoated tablets prepared in Example 9.
%) And sprayed (increased weight: 25 mg / tablet) (High Coater 20) to form a saccharide layer. Thereafter, a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight: 8 mg / tablet) to obtain a film-coated tablet.

Example 11 A lactose dispersion (20 w / w%) was sprayed onto the uncoated tablet prepared in Example 9 to give an undercoat (increased weight: 20 mg / tablet) (high coater 20) to form a saccharide layer. did. Thereafter, a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight: 8 mg / tablet) to obtain a film-coated tablet.

Example 12 An uncoated tablet prepared in Example 9 was added to an erythritol aqueous solution (30w).
/ W%) and sprayed (increased weight: 15 mg / tablet) (Hicoater 20) to form a saccharide layer. Thereafter, a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight: 8 mg / tablet) to obtain a film-coated tablet.

Example 13 According to the formulation shown in Table 4, each of Groups I and M was sprayed with a hydroxypropylcellulose solution using a fluidized bed granulator (FD-3SN, manufactured by Powrex), and granulated by a conventional method. did. Each of these two types of granulated powder (1370 g in Group I and 1000 g in M Group) was sized, and 55 g of a disintegrant, Acdizol, and 5 g of magnesium stearate, a lubricant, were added and mixed (tumbler mixer: After that, use a rotary tableting machine (manufactured by Kikusui Seisakusho, Collect 19K) to perform 270 mg /
Uncoated tablets were manufactured. Add an unpurified sucrose aqueous solution (40w)
/ W%) and sprayed (increased weight 10 mg / tablet) (High Coater 20, manufactured by Front Industry Co., Ltd.) to form a saccharide layer on the tablet surface. Thereafter, a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight: 10 mg /
Tablets) to give film-coated tablets.

[0027]

[Table 4]

Example 14 The uncoated tablets prepared in Example 13 were sprayed with lactose-dispersed axillary (20% w / w) to underlay (increased weight: 10 mg / tablet) (Hi Coater 20) to form a saccharide layer. did. Thereafter, a film coating solution using hydroxypropylmethylcellulose, titanium oxide, and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight: 10 mg / tablet) to obtain a film-coated tablet.

Example 15 The uncoated tablets prepared in Example 13 were added to the erythritol aqueous solution (30
(w / w%) was sprayed to give an undercoat (increased weight: 10 mg / tablet) (Hi Coater 20) to form a saccharide layer. Then hydroxypropyl methylcellulose, titanium oxide,
A film coating solution using polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight: 10 mg / tablet) to obtain a film-coated tablet.

Example 16 The uncoated tablet prepared in Example 13 was sprayed with a purified sucrose + talc dispersion solution (4: 1, 50 w / w%) and placed underneath (increased weight: 1).
0 mg / tablet) (Hi Coater 20) to form a saccharide layer. Then, hydroxypropyl methylcellulose, titanium oxide, polyethylene glycol (75: 1
0:15) to perform film coating (increased weight: 10 mg / tablet) to obtain film-coated tablets.

Example 17 The tableting granules produced in Example 13 were made into a caplet type plain tablet of 405 mg / tablet using a rotary launching machine (Kikusui Seisakusho, Collect 19K). Purified sucrose aqueous solution (4
0 w / w%) and sprayed (increased weight: 7 mg / tablet) (Front Sangyo Co., Ltd., Hicoater 20) to form a sugar layer on the tablet surface. Thereafter, a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) was sprayed to perform film coating (increased weight 10 mg /
Tablets) to give film-coated tablets.

Comparative Example 1 The uncoated tablet prepared in Example 1 was sprayed with a film coating liquid using hydroxypropyl methylcellulose, titanium oxide and polyethylene glycol (75:10:15) without spraying. Coating (increased weight: 8 mg / tablet) was performed to obtain a film-coated tablet.

Comparative Example 2 The uncoated tablet prepared in Example 5 was sprayed with a film coating solution using hydroxypropylmethylcellulose, titanium oxide and polyethylene glycol (75:10:15) without spraying. Coating (increased weight: 8 mg / tablet) was performed to obtain a film-coated tablet.

Comparative Example 3 The uncoated tablet produced in Example 9 was directly sprayed with a film coating solution using hydroxypropyl methylcellulose, titanium oxide and polyethylene glycol (75:10:15) without undercoating. Coating (increased weight: 8 mg / tablet) was performed to obtain a film-coated tablet.

Comparative Example 4 The uncoated tablet prepared in Example 13 was sprayed directly with a film coating solution using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) without undercoating. Coating (increased weight: 10 mg / tablet) was performed to obtain a film-coated tablet.

Comparative Example 5 The uncoated tablet prepared in Example 17 was sprayed directly with a film coating liquid using hydroxypropyl methylcellulose, titanium oxide, and polyethylene glycol (75:10:15) without undercoating. Coating (increased weight: 10 mg / tablet) was performed to obtain a film-coated tablet.

EXPERIMENTAL EXAMPLES Samples of Examples 1 to 17 and Comparative Examples 1 to 5 were
5 tablets are stored in a transparent glass bottle and stored at 40 ° C for 4 weeks and 25
Stored at 8 ° C for 8 weeks. Thereafter, the cloudy state of the glass bottle was observed. Table 5 shows the results. Evaluation criteria (-) No bottle fogging (±) Only the lower part of the bottle (tablet contact area) is lightly fogged (+) The whole bottle is lightly fogged (++) The whole bottle is fogged

[0038]

[Table 5] Cloudy state of glass bottle

[0039]

As described above, according to the present invention,
By applying a sugar underhang to an uncoated tablet containing a sublimable component, it is possible to provide an oral solid preparation in which generation of whiskers due to sublimation of the sublimable component and fogging of a heat retaining container are suppressed.

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Claims (6)

[Claims] 1. An oral solid preparation containing a sublimable component and sublimated with a saccharide, wherein the sublimation of the component is suppressed. 2. The oral solid preparation according to claim 1, wherein the weight of the undercoat layer is 2 to 50 parts by weight based on 100 parts by weight of the uncoated tablet. 3. The oral solid preparation according to claim 1, wherein a film coating is applied on an undergarment made of a saccharide. 4. The weight of the film coating is uncoated tablet 10.
The oral solid preparation according to claim 1, wherein the amount is 2 to 10 parts by weight based on 0 part by weight. 5. The oral solid preparation according to claim 1, wherein the sublimable component is ibuprofen. 6. A method for suppressing fogging of a storage container of an oral solid preparation containing a sublimable component, wherein the oral solid preparation is underlined with a saccharide.