JPS6357521A - Oral formulation - Google Patents

Abstract

(57) [Abstract] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an oral preparation of indomethacin, and more particularly to an oral preparation characterized by adding magnesium aluminate L metasilicate.

[Conventional technology]

Indomethacin (1-(p-chlorobenzoyl)-5-
Methoxy-2-methylindole-3=acetic acid, 01g
H16CtNO4 (molecular weight, 357.79) is a non-steroidal anti-inflammatory drug that is widely used as an analgesic and antipyretic drug.

If no treatment is taken, the time to reach the maximum blood concentration of indomethacin from indomethacin preparations ('ImX) is 1 to
3 hours, [Backer et al., Journal of Pharmacology and Experimental Therapeutics (J, Pharmacol.

Exp, -,? her) Volume 153, Page 237, 1
966], [Duggan et al., same journal, vol. 181, no. 563
Page, 1972], [Adams et al., British Journal of Clinical Pharmacology (Br,
J, Clin, Pharmac, ) Volume 14,
p. 286, 1982] It is insufficient as an antipyretic analgesic that requires rapid action.

[Problem that the invention seeks to solve]

An object of the present invention is to provide an oral preparation of indomethacin with a short time to maximum blood concentration (Tmax).

[Means to solve the problem]

In view of the above-mentioned problems, the present inventors have conducted extensive studies and found that by adding 20% or more by weight or more preferably 50 to 200% by weight of magnesium aluminate metasilicate to indomethacin as an additive, it is possible to improve blood flow by increasing blood pressure. Accelerates the time to medium concentration (Tmax) and improves bioavailability.
It is possible to increase

That is, when 10% by weight of magnesium aluminate metasilicate is added to indomethacin, Tmax
Both the area under the blood concentration curve (AUC) and the area under the blood concentration curve (AUC) were the same as the control product, whereas adding 20% by weight resulted in a faster Tmax and better absorption. Furthermore, by adding 100% by weight of F), Tmax becomes approximately % time of the control product,
AUC showed approximately twice the value. Here, by adding magnesium aluminate metasilicate to indomethacin at a ratio of 20% by weight or more, it is fast-acting and
Bioavailability could be increased.

On the other hand, there is no particular restriction on the upper limit of the blending ratio, but if more than three times the amount of indomethacin is blended, the formulation will be bulky, and in practical terms, problems such as an increase in the dose per dose may occur. arise.

Preferably, the amount is 200% by weight or less based on indomethacin, and if the amount is within this range, not only the absorbability of the indomethacin preparation is improved, but there is no problem in the formulation design.

There are no particular restrictions on the dosage form for producing this oral preparation. Examples include tablets, whole granules, fine granules, powders, troches, capsules, and the like.

〔Effect of the invention〕

The indomethacin formulation containing magnesium aluminate metasilicate according to the present invention can exhibit its medicinal efficacy more quickly than conventional formulations. Furthermore, since it is possible to reduce the amount of indomethacin that is required to exert the same medicinal efficacy as conventional drugs, it not only reduces side effects such as ulcer formation, but also results in smaller formulations and lower costs.

(Examples) Hereinafter, the present invention will be specifically explained using Examples and Test Examples.

Example 1 A homogeneous powder mixture consisting of indomethacin 502, low substituted hydroxypropylcellulose 702 and milk 1i 153.5f was prepared and granulated in a conventional manner. Separately, 102 parts of magnesium aluminate metasilicate and 4.5 parts of light anhydrous silicic acid were homogenized. Combine the two powder mixtures and add 12. After adding Of and homogenizing it, it was filled into 2,000 No. 5 capsules by the usual method, and 1
A capsule formulation was obtained as shown below.

Indomethacin 25.00■Magnesium aluminate metasilicate 5.00■Low f
fitM hydroxypropylcellulose 35.00
■Lactose 7
6.75 ■ Light silicic anhydride 2.2
5Wli Talc 6.00
■150.00■ Example 2 According to the method described in Example 1, a capsule formulation having the following composition was manufactured.

Indomethacin 25. OO ■ Magnesium metasilicate aluminate 25.00 ~ Low substituted i Hydroxypropyl cellulose 3s, oo1
rN! lactose
76.75 ■ Light silicic anhydride 2
, 25η Talc 6, OOm9 170.00η Example 3 Magnesium metasilicate aluminate 1507 and light silicic anhydride 602 were mixed and homogenized.

Then lactose 540? , indomethacin 501, starch 850? was added and mixed. Further, 500 ml of hydroxypropyl cellulose was added and dissolved as a binder, and after kneading, 2000 m of granules according to the following formulation were produced per package according to a conventional method.

Indomethacin 25. OC1mq Magnesium metasilicate aluminate 75.00~
Starch 425.00 ■Milk
Sugar 420. O
O ■Light anhydrous acid 30.00■
Hydroquine propyl cellulose 25.00
η1ooo, oo■ Example 4 Magnesium metasilicate aluminate 502, light anhydrous silicic acid 100F, lactose 1750F, and indomethacin 502 were added and mixed.

Add purified water 500 to Sarani Hydroxypovir Cellulose 502 and knead as a binder,
Dry. After that, it is crushed according to the usual method, and each package contains
A 200° packet of the powder shown in the following formulation was manufactured.

Indomethacin 25.0OWl Aluminum metasilicate/magnesium acid 25.00■ Milk
Sugar 875.00■
Light anhydrous silicic acid 5000■Hydroxypropyl cellulose 25.0011!9 Example 5 Indomethacin 50f1 Low substituted hydroxypropyl cellulose 75? A homogeneous powder mixture consisting of lactose and lactose 907 was prepared and granulated using conventional methods. Separately, magnesium metasilicate aluminate 1Q Of, light silicic anhydride 10? was homogenized.

The two powder mixtures were combined, and Merck 152 was added thereto for mixing and homogenization.
7019 (2000 tablets shown in the following formulation were compressed.

Indomethacin 25.00 Magnesium aluminate kimetasilicate 50. OO ■ Low i conversion hydroxypropyl cellulose 37.50 ■
Lactose 45
．． 00 ■ Light silicic anhydride 5, oo
■Talc 7.5o■17
0,00■ Test Example (Test drug) Control drug: Capsule preparation with the following composition manufactured according to the method described in Example 1.

Indomethacin 25.00 ■ Low i-hydroxypropyl cellulose 35.001 ng milk m 76.
y s ■ Light silicic anhydride 2.25
■Talc 6.00■14
5.007'9 Test formulation A: A capsule formulation having the following composition, manufactured according to the method described in Example 1.

Indomethacin 25.00m9 Magnesium aluminate metasilicate 2.50
■Low rt conversion hydroxyglopy cellulose 350
0 ■ Lactose 7
675 Light silicic anhydride 225η
147,50■ Test formulation B: Capsule formulation of Example 1.

Test formulation C: Capsule formulation of Example 2.

A bioavailability evaluation of these four formulations was conducted using four female female peagles.

(Method) A female peagle dog weighing approximately 10 kg was administered on the day before administration.
After fasting for an hour, the test formulation was orally administered with approximately 100 mL of water. The dog was in good condition after administration and did not vomit.

Blood was collected at 0.5, 1, 2, 3 degrees before and after administration.4.
Testing was performed every 6.8 hours via a forelimb vein using a heparinized syringe. The collected blood was centrifuged at 3000 rpm for 10 minutes, and the amount of indomethacin in the plasma was determined by high performance liquid chromatography. Table 1 shows the results.
and shown in Figure 1.

[Brief explanation of drawings]

FIG. 1 is a blood concentration-time characteristic diagram showing the bioavailability test results for the laceration wounds prepared in Examples and the control agent. Patent applicant Taisho Rakuyaku Co., Ltd. Agent Patent attorney Tomi Kitagawa Yariguchi 1

Claims (1)

[Claims] 1) An oral preparation characterized in that 20 to 300% by weight of magnesium aluminate metasilicate is blended with indomethacin.