JPH10279476A - Loxoprofen sodium-containing tablet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject medicine capable of readily preparing and forming in small size so that aged persons can readily swallow it by including magnesium aluminometasilicate. SOLUTION: This medicine is obtained by adding magnesium aluminometasilicate whose water absorption amount is 1.8-2.2 mL/g as additive for pharmaceutical preparation to loxoprofen sodium which is well-known as an analgesic, anti-inflammatory and antipyretic agent. The magnesium aluminometasilicate is formulated in an amount of 10-80 wt.% based on loxoprofen (as anhydride). The medicine is tableted, preferably in 7.5-8.2 mm diameter by well-known method such as dry type granulation or wet type granulation. Thereby, the medicine can be prepared in small size capable of readily ingesting without giving restriction in which total water absorption ability is >=1.7 and without trouble in preparation process. Since the medicine is small- sized tablet, production cost of the medicine can be reduced.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to loxoprofen sodium (chemical name: 2- [4- (2-oxocyclopentan-1-ylmethyl) phenyl] propionic acid sodium salt) which is known as an analgesic, anti-inflammatory and antipyretic agent A novel oral formulation.

[0002]

2. Description of the Related Art Loxoprofen sodium has a problem that it is strongly adhered to a drug or a device / container and easily sticks at the time of tableting. As the preparation, 7-7
No. 4153 describes a loxoprofen sodium-containing preparation (hereinafter referred to as a conventional preparation) having an additive amount of 3 parts by weight or less and a total water absorption capacity of 1.7 or more per 1 part by weight of loxoprofen sodium. I have. Loxoprofen sodium-containing tablets, which are formulated and marketed based on this patent, have a weight of 250 mg per tablet and a diameter of just over 9 mm, and the drug itself exhibits excellent pharmacological action. Regardless, it was difficult for the elderly to swallow and take it with difficulty. In the context of Japan's aging society, it is desirable that drugs with excellent medicinal effects be provided stably and at low cost, and that it is necessary to supply drugs with low resistance to users. It is.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to reduce the size of the preparation so that it can be easily prepared and swallowed by the elderly.
Another object of the present invention is to provide a loxoprofen sodium-containing tablet having a low production cost. The tablet of the present invention has been considered to be a problem in conventional preparations, and is disclosed in Japanese Patent Publication No. 7-741.
Even if the total water absorption capacity defined in JP-A-53-53 is less than 1.7, there is an advantage that a tablet can be formed without problems such as tableting trouble. As described above, the present invention is epoch-making in view of the fact that loxoprofen sodium-containing tablets could be conventionally formulated only under the constraint of a total water absorption capacity of 1.7 or more.

[0004]

Means for Solving the Problems The present inventors blended magnesium loxaprofen sodium as a pharmaceutical additive with sodium loxoprofen to prevent tableting disorders, facilitate swallowing by the elderly, and reduce the size. Loxoprofen sodium-containing tablets have been provided, and have completed the present invention. That is, the present invention
The present invention relates to a loxoprofen sodium-containing tablet which contains magnesium aluminate metasilicate as a pharmaceutical additive.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Loxoprofen sodium, which is an active ingredient compound of the present invention, can be produced by Japanese Patent Publication No. 58-4699 and an improved production method. You may. The amount of loxoprofen sodium was 60 mg per tablet as an anhydride (6 mg as a dihydrate) as in the commercial product.
8.1 mg) is preferred. Magnesium aluminate metasilicate formulated in the present invention is an essential additive (blended as an excipient) in order to reduce the size of the final preparation, and its amount is 1% of loxoprofen sodium as an anhydride.
0 to 80% by weight is preferred. The ai value of the present magnesium metasilicate aluminate as defined in JP-B-7-74153 is 2.0.

The tablets provided by the present invention are preferably plain tablets, and may be sugar-coated tablets, film-coated tablets, long-acting tablets and the like. Its weight is lighter than a commercial product, and is preferably 200 mg or less. The diameter is preferably 6 mm or more and less than 9 mm, and preferably 7.5 mm.
８8.2 mm. Since the total amount of additives per tablet is small and small tablets, about 30
%, Which is advantageous in terms of cost.

In producing the tablet of the present invention, other known pharmaceutical additives can be blended. As these additives, powdered lactose (ai value defined by Japanese Patent Publication No. 7-74153: 0.18, the same applies hereinafter), magnesium aluminate silicate, synthetic aluminum silicate, synthetic hydrotalcite, dry aluminum hydroxide gel , Magnesium oxide, sucrose, mannitol, corn starch (0.6), potato starch, microcrystalline cellulose (1.0), hydroxypropyl cellulose (0.
1), low-substituted hydroxypropylcellulose (2.
0), hydroxypropylmethylcellulose, hydroxyethylcellulose, calcium hydrogen phosphate, anhydrous calcium hydrogenphosphate, precipitated calcium carbonate, hydroxypropyl starch (0.5), dextrin, carboxymethylcellulose (2.0), carboxymethylcellulose calcium ( 2.0), sodium carboxymethyl starch (0.2), cyclodextrins, polyvinylpyrrolidone, polyvinyl alcohol, alginic acid (1.5), calcium silicate, amorphous silicic anhydride (1.0), talc (0.3), iron sesquioxide, magnesium stearate and the like. The final tablet can be prepared by known methods such as dry granulation or wet granulation together with loxoprofen sodium as an active ingredient and magnesium aluminate metasilicate as an essential additive. Test Example Per tablet, loxoprofen sodium (as dihydrate) 68.1 mg, corn starch 16 mg,
Sodium carboxymethyl starch 10mg, lactose 6
7 mg was mixed under the fluidized bed, and water was sprayed to perform fluidized bed granulation. Then, dry until the exhaust temperature reaches 45 ° C.
The mixture was sized through a 4-mesh sieve. The following amount of magnesium metasilicate aluminate (additive A, NS2N, water absorption: 1.8-2.2 mL / g), the following amount of low-substituted hydroxypropylcellulose (LH-31, additive B):
1 mg of talc and 1 mg of magnesium stearate were added and mixed. The resulting mixture was set on a tableting machine (Clean Press Collect 12HUK, Kikusui Seisakusho) with a flat and engraved punch having a diameter of 8 mm and a tableting pressure of 1.2 ton, a tablet weight of 190 mg (60 mg of anhydrous loxoprofen sodium). ). The total water absorption capacity of the tablets is 1.6. The tablets obtained were white and all had a thickness of about 3.0 mm. The hardness was measured by a tablet continuous measurement system (Japan Machinery Co., WHT-2), and the disintegration time was measured by the method prescribed by the Japanese Pharmacopoeia (test solution: water, no auxiliary plate), and the results were as follows. . ──────────────────────────────────── No Additive A Additive B Hardness Disintegration time (mg / 1 Tablet) (mg / 1 tablet) (kp) (min) ──────────────────────────────────── 1 0 35 13.3 14.5 2 5 30 14.3 12.6 3 10 25 15.0 12.5 4 15 20 15.0 11.1 5 20 15 14.7 11.7 6 30 15 15. 4 15.9 7 35 0 14.6 38.0 Ｎｏ No . In the tablets of Nos. 1 and 2, troubles such as sticking and stamping were observed at the time of tableting. The tablets Nos. 3 to 7 had no tableting trouble and no abnormal appearance.

[0008]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto. Example 1 68.1 mg of loxoprofen sodium (as dihydrate), 35 mg of magnesium aluminate metasilicate, 16 mg of corn starch, 10 mg of carboxymethyl starch sodium and 10 mg of lactose per tablet were mixed under a fluidized bed, Water was sprayed to perform fluidized bed granulation.
Subsequently, drying was performed until the exhaust temperature reached 50 ° C. The dried product was sieved with a 24 mesh sieve, and 1 mg of talc and 2 mg of magnesium stearate were added and mixed. Using a flat punch with a stamp of 8 mm in diameter, the resulting mixture was tableted at a tableting pressure of 0.8 ton and a tablet weight of 190 mg (60 mg as anhydrous loxoprofen sodium) for a total of 10,000 tablets. Despite the fact that the total water absorption capacity of this tablet is 1.6 and less than 1.7, no troubles such as sticking and punching out were observed in the tableting process, and the thickness of the obtained tablet was 3.1 mm. The disintegration time (test solution: water, without auxiliary board) according to the Japanese Pharmacopoeia method is 10
Min, Schleuniger-4M (Freund Corporation)
Was 15 kp. Example 2 68.1 mg of loxoprofen sodium (as dihydrate), 15 mg of magnesium aluminate metasilicate, 16 mg of corn starch, 20 mg of low-substituted hydroxypropylcellulose, 20 mg of low-substituted hydroxypropylcellulose, 10 mg of sodium carboxymethyl tartrate, trace amount of iron sesquioxide per tablet Then, an appropriate amount of lactose was mixed under the fluidized bed, and 2.5 mg of a 2% aqueous solution of hydroxypropylcellulose was sprayed as a solid content to perform fluidized bed granulation. Subsequently, drying was performed until the exhaust temperature reached 45 ° C. The dried product is sieved with 24 mesh, and talc 1
mg and 2 mg of magnesium stearate.
The mixture was mixed for 10 minutes using a mold mixer. The resulting mixture was pressed with a tableting pressure of 1.2 to using a flat punch having a diameter of 8 mm.
n A total of 35,000 tablets were pressed with a tablet weight of 190 mg (60 mg as anhydrous loxoprofen sodium). Although the total water absorption capacity of the tablet was 1.6, which was less than 1.7, no troubles such as sticking and stamping were found in the tableting process. The obtained pale red tablet had a thickness of 3.0 mm, a disintegration time of 8 minutes and a hardness of 12 kp. Example 3 68.1 mg of loxoprofen sodium (as a dihydrate), 25 mg of magnesium aluminate metasilicate, 16 mg of corn starch, 10 mg of low-substituted hydroxypropylcellulose, 5 mg of sodium carboxymethyl starch and 5 mg of a suitable amount of lactose were flowed per tablet. The mixture was mixed under the layer, and 2.5 mg of a 2% aqueous solution of hydroxypropylcellulose was sprayed as a solid content to perform fluidized bed granulation. Subsequently, drying was performed until the exhaust temperature reached 45 ° C. The dried product is sized with a 24 mesh sieve, and 1 mg of talc and 2 mg of magnesium stearate are added.
Mix for minutes. Using a flat punch having a diameter of 8 mm, the obtained mixture was tabletted at a tableting pressure of 1.0 ton and a tablet weight of 190 mg (60 mg as anhydrous loxoprofen sodium) for a total of 35,000 tablets. The total water absorption capacity of this tablet is 1.6,
Despite being less than 1.7, no troubles such as sticking and missing stamping were observed in the tableting process. The resulting tablet had a thickness of 3.0 mm, a disintegration time of 10 minutes, and a hardness of 14 kp.
Met.

[0009]

According to the present invention, by adding magnesium aluminate metasilicate to loxoprofen sodium as a pharmaceutical additive, the total water absorption capacity is not limited to 1.7 or more, and there is no trouble in the formulation process, and it is compact, and has an aging effect. A loxoprofen sodium-containing tablet is provided which is easy to take for a person and has a low production cost.

Claims (3)

[Claims] 1. A loxoprofen sodium-containing tablet containing magnesium aluminate metasilicate as a pharmaceutical additive. 2. The tablet according to claim 1, wherein the amount of the magnesium aluminate metasilicate is 10 to 80% by weight of loxoprofen sodium (as an anhydride). 3. The tablet according to claim 1, further comprising a magnesium metasilicate aluminate having a water absorption of 1.8 to 2.2 mL / g.