JPH0710758A - Long acting cefaclor pharmaceutical preparation - Google Patents

Abstract

PURPOSE:To obtain the subject pharmaceutical preparation, useful for imparting an effective blood level of cefaclor for a long period after the oral administration, producible without using an organic solvent and useful for improving the working environment or reducing the production cost. CONSTITUTION:This long acting cefaclor pharmaceutical preparation contains a rapidly soluble cefaclor pharmaceutical preparation and a delayed soluble cefaclor pharmaceutical preparation at about 4:6 ratio expressed in terms of cefaclor potency. The delayed soluble cefaclor pharmaceutical preparation is composed of the rapidly soluble pharmaceutical preparation provided with an enteric coating eluting at about pH 6. The charcteristic of the long acting cefaclor pharmaceutical preparation is that the enteric coating contains hydroxypropyl methyl cellulose acetate succinate and triethyl citrate and coated in an amount of 30-60wt.% based on the weight of the rapidly soluble cefaclor pharmaceutical preparation before coating.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a cefaclor sustained-release preparation. More specifically, it relates to a long-acting preparation capable of sustaining the action of cefaclor.

[0002]

2. Description of the Related Art Since the absorption site of cefaclor is the upper part of the small intestine, the elution pH of the slow-dissolving component is important for the production of a sustained-release cefaclor preparation. However, there is a problem that the bioavailability is lowered in the high pH range where the elution pH is high. As a means for solving this problem, a method of coating an enteric coating of a slow-dissolving component with a coating composed of methacrylic acid and a methyl methacrylic acid methyl ester copolymer, shellac, glycerin fatty acid ester and talc (Japanese Examined Patent Publication No. No. 32166) is known. Also, regarding the related substance cephalexin, a method of coating a similar composition (Japanese Patent Publication No. 61-13683) is disclosed. However, all of these methods have a problem that a large amount of organic solvent is required for preparing the coating solution and a great amount of time is required in the manufacturing process.

An enteric coating method using an aqueous dispersion system (Japanese Patent Laid-Open No. 59-19025) is also known, but hydroxypropylmethylcellulose acetate succinate, which is an aqueous dispersion enteric base material, has a different dissolution pH. However, there is a problem that cefaclor has insufficient sustainability or bioavailability is reduced unless a solution having an appropriate dissolution pH is used.

[0004]

SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide a cefaclor preparation which exhibits good bioavailability and durability. It is also an object of the present invention to provide a sustained-release cefaclor preparation that can be produced without using a special preparation raw material or an organic solvent in the preparation.

[0005]

Means for Solving the Problems As a result of diligent efforts to solve the above-mentioned problems, the present inventors have developed a continuous cefaclor preparation containing a fast-dissolving cefaclor preparation and a slow-dissolving cefaclor preparation in a ratio of about 4: 6. The above-mentioned problems can be solved by using an enteric-coated granular agent containing hydroxypropylmethylcellulose acetate succinate, which is a water-dispersed enteric-coated agent, and having an elution pH of around 6 as the slow-soluble cefaclor preparation. As a result, they have found that they can be achieved and have completed the present invention. That is, the present invention is a continuous cefaclor preparation containing a fast-dissolving cefaclor preparation and a slow-dissolving cefaclor preparation in a ratio of about 4: 6 in terms of cefaclor titer, wherein the slow-dissolving cefaclor preparation is eluted at a pH of about 6. A fast-dissolving cefaclor preparation having an enteric coating, wherein the enteric coating contains hydroxypropylmethylcellulose acetate succinate and triethyl citrate in a proportion of 30 to 60% by weight based on the weight of the fast-dissolving cefaclor preparation before coating. The present invention provides a sustained-release cefaclor preparation. According to a preferred embodiment of the present invention, the hydroxypropylmethylcellulose acetate succinate has an acetyl group of 7.0 to 14.0.
%, The succinoyl group is in the range of 4.0 to 14.0%.

The fast-dissolving cefaclor preparation contained in the preparation of the present invention is a known preparation, for example, JP-B-62-321.
The fast-dissolving cefaclor preparation described in Japanese Patent No. 66 can be used. Such a fast-dissolving cefaclor preparation is generally a granule, and may be formed into a form of granules or fine granules by a known wet extrusion granulation method, or a stirring granulation method or a tumbling granulation method. It can be manufactured. The slow-dissolving cefaclor preparation contained in the preparation of the present invention is, for example, 20
It can be produced by using the above fast-dissolving cefaclor formulation granulated to a particle size of about 48 mesh and applying an enteric coating to the formulation. It is preferable that the same formulation as the fast-dissolving cefaclor formulation contained in the formulation of the present invention is subjected to enteric coating to produce a slow-dissolving cefaclor formulation.

The enteric coating applied to the slow-dissolving cefaclor formulation of the formulation of the present invention comprises the enteric base hydroxypropylmethylcellulose acetate succinate and the plasticizer triethyl citrate. The coating is 30 to 30% by weight based on the weight of the above-mentioned fast-dissolving cefaclor preparation to which the enteric coating is applied.
It is preferably applied at a rate of 60% by weight. The slow-dissolving cefaclor preparation coated with the enteric coating in such a proportion has good acid resistance and shows rapid dissolution in the dissolution pH range.

The dissolution pH of the slow-dissolving cefaclor preparation is preferably about 6. For example, if the acetyl group is 7.0
A slow-dissolving cefaclor preparation is produced by applying an enteric coating using hydroxypropylmethylcellulose acetate succinate, which is an enteric-based agent having an amount of 14.0% and a succinoyl group in the range of 4.0 to 14.0%. You can Also, for example, MF type and HF type are 4:
Although a mixture of 6 to 6: 4 may be used as an enteric coating agent to produce a slow-dissolving cefaclor preparation,
The slow-dissolving cefaclor formulations coated with MF-type and HF-type hydroxypropylmethylcellulose acetate succinate were mixed at a ratio of 4: 6 to 6: 4 to prepare a slow-dissolving cefaclor formulation of the present invention. You may use.

Triethyl citrate used as a plasticizer is about 30% by weight based on the weight of hydroxypropylmethylcellulose acetate succinate which is an enteric base.
It is preferable to add it in the ratio of. The enteric coating may include talc as a bulking agent. Since talc is a bulking agent for the coating and has an effect of preventing adhesion between particles in the coating process, it is preferable to add it in a ratio of about wt% relative to the weight of hydroxypropylmethylcellulose acetate succinate. The enteric coating can be performed by a coating method well known to a person skilled in the art, preferably using an aqueous suspension containing the above-mentioned components in a proportion of ˜wt%.
For example, a spray coating method can be used.

The sustained-release cefaclor preparation of the present invention is a preparation containing the above fast-dissolving cefaclor preparation and slow-dissolving cefaclor preparation in a ratio of about 4: 6 in terms of cefaclor titer. In order to produce the formulation of the present invention,
For example, a fast-dissolving cefaclor preparation and a slow-dissolving cefaclor preparation, which are manufactured in the form of granules, are mixed so as to have a cefaclor titer of about 4: 6, or a granule is manufactured, or manufactured in this manner. The granules thus prepared may preferably be filled into capsules.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. Reference Example 1 200 g of cefaclor, corn starch 17.5
g, D-mannitol 8.75 g, carboxymethylcellulose Ca 15 g, mixed powder, Macrogol 6000,
75 g of hydroxypropyl cellulose aqueous solution was added and kneaded, and granulated by an extrusion granulator. After drying with a fluid bed granulator, the granules were sized with a 20-30 mesh sieve to produce a fast-dissolving cefaclor preparation. Reference Example 2 Fast-dissolving cefaclor preparation 200 obtained in Reference Example 1
For g, 360 g of coating liquid having the following composition
Was sprayed using a fluidized bed coating machine to produce a slow-dissolving cefaclor formulation. AQOAT MF 5.0% 18g AQOAT HF 5.0% 18g Triethyl citrate 3.3% 12g Talc 3.3% 12g Water 83.4% 300g Total 100.0% 360g Reference Example 3 Obtained by Reference Example 1 Fast-dissolving cefaclor preparation 200
For g, 360 g of coating liquid having the following composition
Was sprayed using a fluidized bed coating machine to produce a slow-dissolving cefaclor formulation. AQOAT MF 10.0% 36 g Triethyl citrate 3.0 % 10.8 g Talc 5.0% 18 g Water 82.0% 295.2 g Total 100.0% 360 g Reference Example 4 Obtained by Reference Example 1 Fast-dissolving cefaclor preparation 200
For g, 360 g of coating liquid having the following composition
Was sprayed using a fluidized bed coating machine to produce a slow-dissolving cefaclor formulation. AQOAT HF 10.0% 36 g triethyl citrate 3.0 % 10.8 g talc 5.0% 18 g water 82.0% 295.2 g total 100.0% 360 g Example 1 Obtained according to Reference Example 1. The fast-dissolving cefaclor preparation and the slow-dissolving cefaclor preparation obtained in Reference Example 2 were mixed at a ratio of 4: 6 in terms of cefaclor potency, and each capsule was made to have a titer of 187.5 mg. Filled. Example 2 Cefaclor titer Mix so that the conversion becomes 4: 6,
Each package was packaged so that the titer was equivalent to 375 mg.
The usefulness of the preparation of the present invention was examined using the capsule of Example 1. When the capsule concentration was orally administered to multiple healthy volunteers and the blood concentration of cefaclor was examined, it was revealed that the formulation of the present invention was rapidly absorbed and the blood concentration was maintained for a long time. It was

[0012]

INDUSTRIAL APPLICABILITY The sustained-release cefaclor preparation of the present invention is useful because it gives an effective blood concentration of cefaclor over a long period of time after oral administration. Further, it can be manufactured without using an organic solvent, which is useful for improving the working environment and reducing the manufacturing cost.

Claims (2)

[Claims] 1. A continuous cefaclor preparation containing a fast-dissolving cefaclor preparation and a slow-dissolving cefaclor preparation in a ratio of about 4: 6 in terms of cefaclor titer, wherein the slow-dissolving cefaclor preparation is eluted at pH about 6 A fast-dissolving cefaclor formulation with a soluble coating, wherein the enteric coating comprises hydroxypropylmethylcellulose acetate succinate and triethyl citrate, and 3% by weight of the fast-dissolving cefaclor formulation before coating.
A sustained-release cefaclor formulation, characterized in that it is applied in a proportion of 0 to 60% by weight. 2. The hydroxypropylmethylcellulose acetate succinate has 7.0 to 14.0% acetyl groups,
The succinoyl group is in the range of 4.0 to 14.0%.
The described formulation.