JPH09100229A - Solid preparation containing loxoprofen sodium - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a solid preparation containing loxoprofen sodium and having decreased adhesiveness. SOLUTION: The solid preparation contains an additive such as microcrystalline cellulose, hydroxypropyl cellulose having low substitution degree, lactose or magnesium stearate compounded in an amount to give a total water-feeding capacity of >=1.7, preferably >=2.0. The mixture is prepared in the form of a solid preparation such as tablet, capsule, granule or powder e.g. by dry or wet-mixing method. The addition of the additive in an amount to get a total water-feeding capacity exceeding a specific level effectively prevents the blocking of the composition caused by the adhesion to the machine in tableting or encapsulation, the adhesion of the drug component to a vessel and the agglomeration of drugs. Loxoprofen sodium has a chemical name of 2-[4-(2- oxocyclopentan-1-ylmethyl)phenyl]propionic acid sodium salt and is useful as an analgesic anti-inflammatory antipyretic agent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to loxoprofen
It relates to a solid preparation containing sodium.

[0002]

2. Description of the Related Art Loxoprofen sodium (chemical name: 2- [4- (2-oxocyclopentan-1-ylmethyl) phenyl] propionic acid sodium salt), an analgesic, anti-inflammatory and antipyretic agent, is used for drugs, equipment and containers. Strong adhesion. Therefore, it is difficult to formulate a drug unless a formulation that takes this fact into consideration is taken into consideration, and even if the drug can be formulated, it is not possible to prepare a drug product having suitable properties as a drug.

Conventionally, as an improved formulation for such an adhesive drug, there is a formulation in which a large amount of a lubricant such as magnesium stearate is used, or drug particles or particles containing a drug are coated. . However, when the former is applied to loxoprofen sodium, the disintegration, dissolution property and bioavailability of the preparation are impaired, and when it is made into a tablet, there is a drawback that its hardness is significantly reduced. . Also, when the latter is applied to loxoprofen sodium, the use of solvent and a long and complicated process result in an increase in formulation cost and a decrease in bioavailability depending on the coating agent used. And the like.

[0004]

DISCLOSURE OF THE INVENTION The present inventors have conducted various studies on the reduction of the adhesion of loxoprofen / sodium, and as a result, by adding an additive so as to have a total water absorption capacity of a certain value or more, The present inventors have found that it is possible to effectively prevent the difficulties that occur when manufacturing a solid preparation, that is, the adhesion of a drug to a machine during tableting or capsule filling, the adhesion of a drug to a container, and the blocking caused by the adhesion of drugs to each other. Completed the invention.

The formulation of the present invention is not only industrially advantageous as compared with the conventional formulation, but also has a wide range of formulations to be selected from the viewpoint of formulation quality, and thus can be formulated without impairing the quality. Have advantages.

[0006]

The present invention relates to a solid preparation containing loxoprofen / sodium, which is prepared by blending the additives so that the total water absorption capacity of the additives is 1.7 or more, preferably 2.0 or more.

The total water absorption capacity of the n kinds of additives of the present invention is given by the following equation.

[0008]

(Equation 1)

M ₀ : Formulation amount of loxoprofen sodium (as an anhydride) m _i : Formulation amount of additive i a _i : Weight of water which can contain a unit weight of the additive i in a “moderate kneading state” Here, the "moderate kneading state" means "a water-containing kneading state suitable for granulation during wet granulation", which is in the Funicular region and below the plastic limit. The following states are experimentally observed. That is, in general, when a powder sample is placed in a mortar, and water is added to this and kneading is performed using a pestle, when the amount of added water is small, it is in a dry state. To do. The "moderate kneading state" of the present invention is a state before shifting to a sticky state,
When the kneaded product is held by the hand, it can retain its shape and is slightly elastic.

The values of a _i of the additives which can be used in the present invention are as follows.

That is, microcrystalline cellulose: 1.0, low-substituted hydroxypropyl cellulose: 2.0, amorphous silicic acid anhydride: 1.0, corn starch: 0.
6, powdered lactose (particle diameter about 12μ): 0.18, hydroxypropyl starch: 0.5, alginic acid: 1.
5, carboxymethyl cellulose: 2.0, carboxymethyl cellulose calcium: 2.0, magnesium stearate: almost negligible value.

The additive usable in the present invention is not particularly limited as long as it does not impair the properties as a medicine.
For example, in addition to the above, dextrin, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, methyl cellulose, amycol, pullulan, mannitol, sucrose, starches, cyclodextrins, polyvinylpyrrolidone, polyvinyl alcohol, various ion exchange resins and the like can be mentioned. it can.

It should be noted that as the particle size of loxoprofen sodium becomes smaller, a better preparation tends to be obtained even if the value of total water absorption capacity is smaller, but a total water absorption capacity of at least 1.7 is required.

The object of application of the present invention is all solid preparations such as tablets, capsules, granules and powders.

The method for producing the preparation is not particularly limited, and any known means such as dry mixing and wet mixing can be used.

[0016]

The present invention will be described in more detail with reference to the following examples, which should not be construed as limiting the invention thereto.

[0017]

Example 1 (1) Manufacturing Method of Preparation The preparation of Example 1 was manufactured as follows.

According to the formulation shown in Table 1 below, loxoprofen sodium, microcrystalline cellulose, lactose and low-substituted hydroxypropyl cellulose were mixed in a mortar, and then an appropriate amount of water was added and kneaded to obtain a kneaded product. It was dried at 60 ° C. for 60 minutes in an aeration dryer. The dried product was sieved through a 30-mesh sieve, magnesium stearate was added thereto, and mixed with a V-type mixer for 10 minutes. The obtained mixture was tabletted using a flat punch having a diameter of 7.5 mm.

The formulation of Control Example 1 was also prepared in the same manner.

[0020]

[Table 1] Parts: Indicates parts by weight.

(2) Results Although the formulation of Example 1 could be tableted, the formulation of Control Example 1 could not be tableted due to "sticking" on the punch.

[0022]

Examples 2 and 3 (1) Manufacturing method of preparations The preparations of Examples 2 and 3 were manufactured as follows.

According to the prescription in Table 2 below, after mixing the respective components except magnesium stearate in a mortar, the mixed powder was dried with a dry pulverizer atomizer (Sample Mill manufactured by Fuji Electric Co., Ltd.) to obtain a φ = 1 mm screen. It was mounted and crushed and mixed. Magnesium stearate was added to the obtained ground product and mixed for 15 minutes with a V-type mixer. The obtained mixture was used as a capsule filling machine (type G manufactured by Hozliger).
KF 700) and capsule filling.

The preparation of Control Example 2 was also prepared in the same manner.

[0025]

[Table 2] Parts: Indicates parts by weight.

(2) Results The preparations of Examples 2 and 3 could be filled, but the preparation of Control Example 2 could not be filled because powder adhered to the rotary filling machine and the spindle, which could damage the filling machine. .

[0027]

EFFECT OF THE INVENTION The solid preparation containing loxoprofen / sodium according to the present invention showed an excellent effect in reducing the adhesiveness.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 47/38 A61K 47/38 B

Claims (1)

[Claims] 1. A solid preparation containing loxoprofen / sodium, wherein the additive is blended so that the total water absorption capacity of the additive is 1.7 or more.